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September 1, 2023

MedChem Partners and Tufts Medical School Professor Elizabeth Fini paper published.

Lexington, MA, September 1^st – The collaborative work of MedChem Partners and Dr. Fini titled “Regulatory Effects of GPR158 Overexpression in Trabecular Meshwork Cells of the Eye’s Aqueous Outflow Pathways” has been published in the journal Stresses.

Elevated intraocular pressure (IOP), the major risk factor for glaucoma, is caused by decreased outflow through the trabecular meshwork (TM). The pathophysiology of ocular hypertension has been linked to stress pathways, including fibrosis, calcification and the unfolded protein response (UPR). In a pharmacogenomic screen, we previously identified the novel G-protein-coupled receptor (GPCR), GPR158, showed that expression is upregulated in TM cells by glucocorticoid stress hormones, and showed that overexpression protects against oxidative stress. We also found that loss of Gpr158 in knockout mice negates IOP reduction due to treatment with the catecholamine stress hormone, epinephrine. An increase in GPR158 would be expected to alter the activity of GPR158- regulated pathways. Here, we profiled gene expression changes due to GPR158 overexpression by microarray, then conducted pathway analysis. We identified five upstream stress regulators relevant to ocular hypertension: dexamethasone and TGFB1 (fibrosis), XBP1 and ATF4 (UPR), and TP53 (cell cycle arrest). Key genes in the first three pathways were downregulated by GPR158 overexpression, but not enough to inhibit dexamethasone-induced fibrosis or calcification in TM cells, and loss of Gpr158 in knockout mice only minimally protected against dexamethasone-induced ocular hypertension. Depending on dose, GPR158 overexpression down- or upregulated the TP53 pathway, suggesting the mechanism for previously observed effects on cell proliferation. A sixth upstream regulator we identified was a GPCR: the beta-adrenergic receptor ADRB1. Adrenergic receptors serve as targets for IOP-lowering drugs, including epinephrine. These data provide new information about pathways regulated by GPR158.

Suarez, M.F.; Itakura, T.; Pany, S.; Jeong, S.; Chintala, S.K.; Raizman, M.B.; Riesinger, S.; Lazarova, T.; Echenique, J.; Serra, H.M.; et al. “Regulatory Effects of GPR158 Overexpression in Trabecular Meshwork Cells of the Eye’s Aqueous Outflow Pathways.” Stresses 2023, 3, 629–652. https://doi.org/10.3390/stresses3030044

July 28, 2023

MedChem Partners and University of Vermont collaborators paper published

Lexington, MA, July 28^th – The collaborative work of MedChem Partners and Drs Dale and Vernon Walker titled “WR1065 conjugated to thiol-PEG polymers as novel anticancer prodrugs: broad spectrum efficacy, synergism, and drug resistance reversal” has been published in the journal Frontiers in Oncology.

The lack of anticancer agents that overcome innate/acquired drug resistance is the single biggest barrier to achieving a durable complete response to cancer therapy. To address this issue, a new drug family was developed for intracellular delivery of the bioactive aminothiol WR1065 by conjugating it to discrete thiol- PEG polymers: 4-star-PEG-S-S-WR1065 (4SP65) delivers four WR1065s/ molecule and m-PEG6-S-S-WR1065 (1LP65) delivers one. Infrequently, WR1065 has exhibited anticancer effects when delivered via the FDA-approved cytoprotectant amifostine, which provides one WR1065/molecule extracellularly. The relative anticancer effectiveness of 4SP65, 1LP65, and amifostine was evaluated in a panel of 15 human cancer cell lines derived from seven tissues. Additional experiments assessed the capacity of 4SP65 cotreatments to potentiate the anticancer effectiveness and overcome drug resistance to cisplatin, a chemotherapeutic, or gefitinib, a tyrosine kinase inhibitor (TKI) targeting oncogenic EGFR mutations. The CyQUANT®-NF proliferation assay was used to assess cell viability after 48-h drug treatments, with the National Cancer Institute COMPARE methodology employed to characterize dose-response metrics. In normal human epithelial cells, 4SP65 or 1LP65 enhanced or inhibited cell growth but was not cytotoxic. In cancer cell lines, 4SP65 and 1LP65 induced dose-dependent cytostasis and cytolysis achieving 99% cell death at drug concentrations of 11.2 ± 1.2 μM and 126 ± 15.8 μM, respectively. Amifostine had limited cytostatic effects in 11/14 cancer cell lines and no cytolytic effects. Binary pairs of 4SP65 plus cisplatin or gefitinib increased the efficacy of each partner drug and surmounted resistance to cytolysis by cisplatin and gefitinib in relevant cancer cell lines. 4SP65 and 1LP65 were significantly more effective against TP53-mutant than TP53-wild- type cell lines, consistent with WR1065-mediated reactivation of mutant p53. Thus, 4SP65 and 1LP65 represent a unique prodrug family for innovative applications as broad-spectrum anticancer agents that target p53 and synergize with a chemotherapeutic and an EGFR-TKI to prevent or overcome drug resistance.

Walker DM, Lazarova TI, Riesinger SW, Poirier MC, Messier T, Cunniff B and Walker VE (2023) “WR1065 conjugated to thiol-PEG polymers as novel anticancer prodrugs: broad spectrum efficacy, synergism, and drug resistance reversal.” Front. Oncol. 13:1212604. doi: 10.3389/fonc.2023.1212604

August 2, 2022

MedChem Partners LLC and SBH Sciences have teamed up to offer an integrated solution for drug discovery

Lexington, MA, and Natick, MA, August 2^nd, 2022– MedChem Partners LLC and SBH Sciences announced today a scientific collaboration focused on a tighter integration between MedChem Partners’ chemistry capabilities and SBH’s biology and assay technologies. SBH sciences has been a leader in biology for 24 years and provides services in the area of biomarkers, cell-based assays and cell culture, gene therapy, drug discovery, protein production and purification, and in vitro assay development and screening. MedChem Partners has been providing high level chemistry services for 17 years, and has expertise in synthetic and medicinal chemistry, conjugation chemistry, stable label isotope and reference standard preparation, pre-formulation and lipid chemistry, program planning and NewCo formation.

The current collaboration is designed to bring both companies platforms into alignment, allowing for the Integration of chemistry and biology to streamline discovery, screening, and medicinal chemistry. By removing the barriers between chemistry and biology, the current collaboration will allow for the free flow of information in discovery and development programs, accelerating the pace at which these programs can progress. In addition, rather than a “hand off” between chemistry and biology, the current collaboration will allow a smooth transition where institutional knowledge is passed on rather than lost.

“The power in this collaboration is that we both focus on our area of expertise: SBH has a very broad and deep understanding of biology, whereas we have decades of expertise in a variety of chemistries. Together we can leverage the knowledge base of each other to provide a lot of juice to jumpstart discovery and development programs”—Steven Riesinger, CEO, MedChem Partners

For more Information:

MedChem Partners SBH Sciences 99 Hayden Ave. Suite 210 4 Strathmore Road Lexington, MA 02421 Natick, MA 01760 Phone: (781) 676-2000 xt 303 Phone: (508) 650-6218 Email: info@medchempartners.com Email: rnir@SBHsciences.com

About MedChem Partners

MedChem Partners is a medicinal chemistry service provider offering comprehensive medicinal chemistry support to biotechs, pharmaceutical companies and academic laboratories engaged in research and drug discovery. The company’s expertise covers all aspects of medicinal chemistry, from strategic planning to hit evaluation and validation to lead optimization and pre-clinical development. MedChem Partners provides both consulting services as well as hands on synthesis and wet chemistry. Located just outside Boston, our modern laboratories are outfitted with all of the equipment necessary to perform organic synthesis and medicinal chemistry including NMR, LC/MS and automated chromatography systems. For more information, visit us at www.MedChemPartners.com

About SBH Science

SBH Sciences is a bio-incubator and innovative preclinical Contract Research Organization (CRO) focused on cytokines, anti-cancer, and anti-inflammation drug development. We are offering extensive products and services including 31 recombinant cytokines, 8 Glycosyltransferase enzymes, 33 monoclonal antibodies and the analysis of over 150 Biomarkers using 11-platform.

SBH Sciences is the world leader in cell-based assays using over 500 cancer cell lines and performing 330 cell-based assays for cytokines and chemokines, and has provided services to over 250 biotechnology and diagnostics companies across the globe during our 24 years of business. For more information, visit us at www.sbhsciences.com

July 4, 2022

MedChem Partners publishes paper with Collaborators Mihail Climov of West Virginia University and Dennis Orgill of Harvard Medical School

Lexington, MA, July 4^th ,2022 – The work of MedChem Partners and their collaborators at University of West Virginia and Harvard Medical school has been published in the journal Plastic Reconstructive & Regenerative Surgery titled “A novel nitric oxide-releasing gel for diabetic wounds.”

Diabetic foot ulcers represent a major healthcare problem. Externally delivered Nitric Oxide (NO) is a potent modulator of wound healing capable of accelerating diabetic wound healing. Currently, the most common delivery method to the wound is in gaseous form. Such practice is dangerous and not cost-efficient. The current work explores a novel paradigm of NO delivery in form of a stable, nontoxic gel that produces NO when in contact with wound exudate. This hypothesis was tested in vivo on a murine diabetic wound model. A total of 4 experimental groups (n=12), two concentrations: 100 μM, 1000 μM, and two controls: a gel-control, and the untreated groups were tested. Wound contraction was assessed by planimetry for a duration of one week. Granulation tissue, CD31, and α-SMA expressions were measured at the end of the tested period.

Although no statistically significant difference in wound healing kinetics between the experimental groups was found, the histological evaluation showed a significant increase in granulation tissue thickness in both Gel 100 and Gel-control (p < 0.05). Gel 100 exhibited a significant impact on the expression of angiogenesis markers CD31 and α-SMA (p < 0.05). Gel 1000 appears to have an inhibitory effect on angiogenesis as compared to Gel 100.

This preliminary study showed that the NO gel used has a dose-dependent effect on CD31, α-SMA resulting in regulation of granulation tissue formation during wound healing in diabetic murine models. While these preliminary studies show the potential of this treatment, further studies to optimize these compounds are needed.

Yukun Liu, Songxue Guo, Shuyi Wei, Huan Wang, Yong Liu, Andrea V. Moscoso, Zina Ribkovskaia, Tsvetelina Lazarova, Steven Riesinger, Dennis P. Orgill, Mihail Climov (2022)” A novel nitric oxide-releasing gel for diabetic wounds. PRRS 2022; 1:24-33. https://doi.org/10.57604/PRRS-004

Janurary 21, 2022

MedChem Partners and Harvard Collaborator Professor Henry Querfurth paper published

Lexington, MA, January 21^st – The work of MedChem Partners’ collaborator at Harvard university have published the collaborative work in the journal PLoS ONE titled “A PDK-1 allosteric agonist neutralizes insulin signaling derangements and beta-amyloid toxicity in neuronal cells and in vitro”

The Alzheimer’s brain is affected by multiple pathophysiological processes, which include a unique, organ-specific form of insulin resistance that begins early in its course. An additional complexity arises from the four-fold risk of Alzheimer’s Disease (AD) in type 2 diabetics, however there is no definitive proof of causation. Several strategies to improve brain insulin signaling have been proposed and some have been clinically tested. We report findings on a small allosteric molecule that reverses several indices of insulin insensitivity in both cell culture and in vitro models of AD that emphasize the intracellular accumulation of b-amyloid (Abi). PS48, a chlorophenyl pentanoic acid, is an allosteric activator of PDK-1, which is an Akt-kinase in the insulin/PI3K pathway. PS48 was active at 10 nM to 1 mM in restoring normal insulin-dependent Akt activation and in mitigating Abi peptide toxicity. Synaptic plasticity (LTP) in prefrontal cortical slices from normal rat exposed to Ab oligomers also benefited from PS48. During these experiments, neither overstimulation of P13K1Akt signaling nor toxic effects on cells was observed. Another neurotoxicity model producing insulin insensitivity, utilizing palmitic acid, also responded to PS48 treatment, thus validating the target and indicating that its therapeutic potential may extend outside of b-amyloid reliance. The described in vitro and cell based in vitro coupled enzymatic assay systems proved suitable platforms to screen a preliminary library of new analogs.

Henry Ouerfurth, John Marshall, Keykavous Paranq, Mengia S. Rioult-Pedotti, Rakesh Tlwari, Bumsup Kwon, Steve Reisinger, Han-Kyu Lee (2022) A PDK-1 allosteric agonist neutralizes insulin signaling derangements and beta-amyloid toxicity in neuronal cells and in vitro PLoS ONE 17(1) e0261696

October 19, 2021

MedChem Partners Patent Allowed

Lexington, MA October 19, 2021 – United States Patent and Trademark Office (USPTO) has issued a Notice of Allowance for the U.S. Patent No. 11,148,999 titled “Nitric oxide donors.” The Patent is based on nitric oxide delivery technology developed and owned by MedChem Partners. Nitric oxide is a signalizing molecule which is implicated in a variety of human disorders. To date, use of nitric oxide has been hampered by the fact that it is a gas which is toxic at high levels, and it has an extremely short half-life in biological matrices. The current invention sequesters nitric oxide chemically as a stable compound which releases nitric oxide predictably over time. These compounds show great promise for controlled delivery of nitric oxide which will find use in the treatment of a variety of disorders.

Find the patent here

July 17, 2021

MedChem Partners and Lead Bio Announce Collaboration to Progress Lead Bio’s CellInject™ Technology for Drug Delivery

Lexington, MA July 7, 2021 – MedChem Partners Lexington, MA and Lead Bio, Sofia, Bulgaria have formed a collaboration to develop Lead Bio’s CellInject™ and I-CAN™ technology for drug delivery. In addition to seeking external investment in this technology through licensing and fee-for service models, MedChem Partners and Lead Bio are also actively engaged in applying this technology to MedChem partners internal nitric oxide delivery program

CellInject™ is a patented lipid nanoparticle delivery which encapsulates and safely transports API through the body fluids such as gastrointestinal fluids, mucus linings, interstitial fluid, and other biological fluids to the target tissues where the drug is released to act locally. It is compatible with most lipophilic APIs in their free non-salt forms and is especially beneficial for substances with low bioavailability, low water solubility, or short half-life.

I-CAN™ Technology is a unique combination of Cellinject™ Technology combined with a mucoadhesive carrier designed for intranasal delivery of drugs. I-CAN™ is designed to resist mucociliary clearance and to cover a large mucus area with а thin continuous film, thus ensuring high absorption of the drug.

Read about Lead Bio here

July 1, 2021

MedChem Partners and University of Vermont Professor Awarded Phase I STTR to Develop Covid-19 Treatment

Lexington, MA July 1, 2021 – MedChem Partners in collaboration with Dr. Vikas Anathy of University of Vermont has been awarded an NSF Phase I STTR grant titled “Novel Inhaled Nitric Oxide Therapy For Pulmonary Treatments (COVID-19)” This grant is awarded to fund collaborative research into the preparation and testing of a variety of nitric oxide releasing analogues which are useful for treating the pulmonary manifestations of Covid-19. The grant, number 2040043, is for one year running from 8/1/2020 through 7/31/2022.

The goal of this grant is to discover and develop synthetic compounds which stably sequester nitric oxide and release it predictably and controllably only in the proper biological environment. These compounds will be delivered to the lung where they will act locally to improve lung function. Since the most devastating effects of Covid-19 are related to Acute Respiratory Distress Syndrome (ARDS), which involves impaired lung function and the associated hypoxia, this strategy shows great promise to ameliorate the most damaging effects of Covid-19 infection. There is a host of scientific literature which shows improved lung function post nitric oxide treatment; however, to date a safe and reliable way to deliver nitic oxide over long periods of time has not been available

The work undertaken in this project will: (i) Prepare a variety of novel NO releasing compounds; (ii) Test analogues for NO release in mouse plasma and lung homogenate, and (iii) Provide proof-of-concept by evaluating NO-releasing compounds in a mouse model of SARS-COV-2-induced ALI-ARDS.

June 28, 2021

MedChem Partners Welcomes Elias Ndaru to Post-doctoral Position

Lexington, MA June28, 2021 – MedChem Partners announces the hire of Elias Ndaru as its newest team member in Lexington MA. Elias is Ph.D in organic chemistry with expertise in various disciplines ranging from Biochemistry, Molecular Biology, Physical and Organic chemistry and Pharmacology. He earned his Ph.D at Binghamton State University where he studied the design, multi-step synthesis and characterization of specific and potent ASCT2 inhibitors Under Prof. Christof Grewer. Prior to his work at Binghamton State, Elias graduated first in class with honors from University of Nairobi, Kenya with a Bachelor of Science in Industrial Chemistry where he studied under Vincent Madadi.

We are very pleased to welcome Elias as the newest member of our team!

May 12, 2021

MedChem Partners Collaborator at Navidea Biopharmaceuticals Present at New York Academy of Sciences Frontiers in Cancer Immunotherapy meeting 2021

New York, NY.,May 12 – May 14, 2021 – MedChem Partners collaborator at Navidea Biopharmaceuticals present a poster at the Frontiers in Cancer Immunotherapy meeting titled “Targeted Delivery of Doxorubicin (DOX) to TAMs Beneficially Alters the Tumor Immune Microenvironment and Synergizes the Activity of Anti-CTLA4

A mannosylated dextran-based drug delivery vehicle (Mw≈ 20kDa) was constructed to deliver DOX payloads to mannose receptor (CD206+) tumor associated macrophages (TAMs). Each vehicle molecule carried 6.5 DOX moieties that were attached via degradable linkers that released DOX upon internalization into TAMs. The DOX-construct was evaluated in human monocyte GM-CSF derived macrophages (CD206+) and in disaggregated immune tumor cells of the CT26 syngeneic mouse tumor model. Changes in immune cells phenotypes were determine by flow cytometry assessments. Control groups were treated with saline, free Dox, or the DOX free construct. In human macrophages assays, the Dox-construct increased expression of CD80, CD86, MHC1, and MHC2 in a dose dependent manner. The increases in CD86 and MHC2 (max 4.7x and 20x respectively) were not replicated by free Dox or vehicle at any dose. In the CT26 model, the same treatments plus anti-CTLA4 alone or with the Dox-construct were tested. No monotherapy reduced tumor growth. The Dox-construct + anti-CTLA4 combination reduced tumor growth 43% (p=.003). The combination treatment also significantly reduced protumor CD163+ TAMs (47%, p=.008) and monocytic myeloid derived suppressor cells (38%, p=.003) while doubling the number of CD8+ T-cells (p=.0004). Results suggest that the DOX-construct may increase the efficacy of anti-CTLA4 immunotherapy.

Ralph, David, Arnold, Jeffery, Riesinger, Steven, and Rosol, Michael Targeted Delivery of Doxorubicin (DOX) to TAMs Beneficially Alters the Tumor Immune Microenvironment and Synergizes the Activity of Anti-CTLA4. NYAS Sciences Frontiers in Cancer Immunotherapy meeting 2021 – Poster presentation

October 5, 2020

Abstract Published

Lexington, MA October 5, 2020 – Abstracts of Presentations from the 2020 Trans-Agency Scientific Meeting on Developing Medical Countermeasures to Treat the Acute and Chronic Effects of Ocular Chemical Toxicity, 25-26 February, Bethesda, Maryland” was published in Toxicology Letters (Volume 331, Supplement 1)

May 3, 2020

MedChem Partners and Collaborators at Tufts Medical Center Present Poster at AVRO Meeting (The Association for Research in Vision and Ophthalmology

Baltimore, MD. May 3-7, 2020 – MedChem Partners and Collaborators at Tufts Medical Center presented a poster titled “Structure-Activity Relationship (SAR) of Dynasore Analogues that Protect the Ocular Surface (OcS)” at the 2020 AVRO Meeting. The poster details research performed in collaboration with Tufts Medical Center on the therapeutic properties of novel compounds Dynsaore and Dyngo-4a, which were recently discovered to be remarkably protective of OcS epithelial cells and their mucosal glycocalyx, preventing damage caused by oxidative stress, thus precluding ocular surface barrier disruption. The poster details their primary results from a SAR study on Dynasore-related compounds versus cytoprotection.

Fini, M Elizabeth ; Pan, Jinhong ; Martínez-Carrasco, Rafael ; Riesinger, Steven ; Lazarova, Tsvetelina. Structure-Activity Relationship (SAR) of Dynasore Analogues that Protect the Ocular Surface (OcS), 2020 AVRO meeting – poster presentation

February 25, 2020

Medchem Partners and Collaborators invited to present at "Developing Medical Countermeasures to Treat the Acute and Chronic Effects of Ocular Chemical Toxicity (A Trans-Agency Scientific Meeting)"

Rockville, Maryland NIH/NIAID Fishers Lane Conference Center February 25-26, 2020 – MedChem Partners and collaborators from Tufts Medical School, USC Medical School, and Mass Eye and Ear were invited to present an oral and poster presentation titled “Dynasore and Analogues Protect the Ocular Surface against Damaging Oxidative Stress”

Vital dyes are used clinically to evaluate ocular surface damage, however staining mechanisms remain poorly understood. Using monolayer cultures of human corneal epithelial cells, we showed that oxidative stress caused by application of tert-butyl hydroperoxide stimulates uptake of vital dyes in parallel with uptake of the transferrin receptor, a marker of receptor-mediated endocytosis. Both dye uptake and endocytosis were blocked by co-treatment with three different inhibitors of endocytosis, suggesting endocytosis as the mechanism of dye uptake. However, a different result was obtained when we used corneal epithelial-equivalent cultures with mucosal differentiation, a better model of the ocular surface. In this case, stress also stimulated dye uptake, but not endocytosis, and two of the three inhibitors were ineffective in blocking dye uptake. These results emphasize the importance of using a valid model of the ocular surface for drawing relevant conclusions. Intriguingly, Dynasore and its more potent analogue Dyngo-4a blocked dye uptake in both models. In ex vivo mouse eyes, Dynasore also blocked dye uptake when treatment was performed at the same time as stress, however it had no effect on dye uptake when the ocular surface was already damaged. Employing cytotoxicity assays and western blotting, we went on to demonstrate that Dynasore is remarkably protective of cells and their mucosal glycocalyx, thus precluding dye uptake. As expected, oxidative stress activated two different pathways of the unfolded protein response (UPR), PERK-CHOP and IRE1. Significantly, Dynasore inhibited the pro-death PERK-CHOP pathway, but not the protective IRE1 pathway. Dynasore compounds target the dynamin family of large GTPases. We are working to identify the specific family member(s) that must be inhibited for ocular surface protection, while also screening for Dynasore analogues that are even more effective in protection of the mucosal epithelia. Recent work has implicated the UPR as a mechanism underlying the pathogenesis of chemical warfare agents. Thus, Dynasore and analogues may be valuable as a countermeasure.

Supported by NIH R01 EY026479, NIH R41 EY030811, Massachusetts Lions Eye Research Fund and Research to Prevent Blindness.

November 14, 2019

MedChem Partners Patent Published

Lexington, MA, November 14, 2019 – World Intellectual Property Organization (WIPO) has published PTC application on which MedChem Partners Steven Riesinger, Tsvetelina Lazarova and Zinaida Ribkovskaia are co-inventors. The patent is titled “Nitric Oxide Donors” (patent publication number 20190345099). This application relates to a novel class of nonoate compounds which exhibit nitric oxide releasing activity and their pharmaceutically acceptable salts, esters and prodrugs. The compounds release nitric oxide upon activation by contact with plasma. The present invention also relates to the use of the disclosed compounds to deliver nitric oxide to treat disorders arising from nitric oxide dysregulation.

October 3, 2019

Patent Allowed

Lexington, MA December 11, 2018 – United States Patent and Trademark Office (USPTO) has issued a Notice of Allowance for the U.S. patent application US 16/214,973 on which MedChem Partners Principle Steven Riesinger is a co-inventor. The patent, titled “Treatment of Cerebral Cavernous Malformations and Cerebral Aneurysms with Rho Kinase Inhibitors” (patent number US2019/0298733) discloses a series of Rho Kinase inhibitors. Rho kinase 2 (ROCK2) is a drug target that plays a key role in propagating biological signals that regulate brain endothelial cell barrier function and this enzyme is frequently overactivated in neurovascular pathologies where barrier function is compromised. In animal models of stroke, reversing the overactivation of ROCK2 that occurs in the vasculature restores endothelial cell barrier function

August 28, 2019

MedChem Partners Awarded Phase I STTR Grant to Study Dynasore Analogues for Treatment of OcS disease in DE

Lexington, MA August 28, 2019 – MedChem Partners in collaboration with Dr. M. Elizabeth Fini of Tufts Medical Center is awarded a Phase I SBIR grant titled ““Dynasore Analogues for Ocular Surface Protection”. This grant is awarded to fund collaborative research into the potential therapeutic properties of the novel compounds Dynasore and Dyngo-4a, which were recently discovered to be remarkable protective of the ocular surface (OcS) barrier and target OcS damage. Many OcS disease are initiated by loss of tear film homeostasis and can be grouped under a syndrome known as dry eye (DE). Currently, anti-inflammatory steroids and small molecules targeting autoimmune T-cell function are the only Food and Drug Administration (FDA)-approved therapeutics. These drugs are not effective in all patients and demonstrate major drawbacks. Dynasore analogues present a novel way of targeting acute effects of DE by providing an alternative entry point to breaking the inflammatory vicious cycle and offering direct protection of the OcS. This may be efficacious in providing rapid relief of eye irritation in acute situations where chronic DE is exacerbated by environmental, and other acute factors. Current FDA-approved drugs do not work acutely.

The long-term goal of this grant is to develop a novel FDA-approved drug based on Dynasore as a potential treatment for OcS disease in DE. The specific work undertaken during Phase 1 of this project is outlined in three specific aims: (i) analyze the structure-activity relationship (SAR) data from ~50 commercially available compounds structurally related to Dynsore and Dyngo-4a and prepare five focused libraries of 12-15 compounds; (ii) test the analogues for activity in OcS barrier protection using a validated human cell culture model of stratified OcS epithelia and determine if the compounds have the capacity to limit endocytosis and if this activity can be isolated from OcS barrier protective activity; (iii) use a well-accepted mouse DS model for chronic human DE to test efficacy of our top three cytoprotective compounds in preventing OcS disease. These compounds will also be assayed for production of inflammatory cytokines and MMP9. We will select the most active compound and compare it to FDA-approved drugs for DE treatment. During Phase II, we will prepare additional compounds to fine-tune efficacy and pharmacokinetic (PK) properties and expand animal testing. We will also examine toxicity or eye irritation, and look for systematic exposure. Finally, we will fine-tune the formulation and dosage to maximize efficacy, shelf life and easy of application, while decreasing any toxic or off target effects that may arise.

May 31, 2019

MedChem Partners and Collaborators at Brigham and Women's Hospital Present at Ohio Valley Society of Plastic Surgeons (OVSPS) 62nd Annual Meeting

French Lick, Indiana, May 31 – Jun 2, 2019 – MedChem Partners collaborators at Brigham and Women’s Hospital give an oral presentation titled “A novel nitric oxide delivery system for diabetic wounds” at the OVSPS 62nd Annual Meeting

This preliminary study showed that the proposed NO gel has a dose-dependent effect on CD31 and α-SMA. While this study shows the potential of this delivery method, further studies to optimize as well as testing remaining formulations are streamlined

March 21, 2019

MedChem Partners Presents Poster at Van Liere Research Day

Morgantown, WV March 21, 2019 – MedChem Partners collaborator Mihail Climov presented a poster titled “A novel nitric oxide delivery system for diabetic wounds” at the Van Liere Research Day, West Virginia University, in Morgantown, W. The poster details research performed in collaboration with Dr. D.P. Orgill of Brigham and Women’s hospital and MedChem partners on the use of novel nitric oxide donors to enhance wound healing.

M.Climov, Y.Liu, S.Guo, S.Wei, H.Wang, Y.Liu, A.V.Moscoso, Z.Ribkovskaia, T.Lazarova, S.Riesinger, D.P.Orgill, A novel nitric oxide delivery system for diabetic wounds, Van Liere Research Day, West Virginia University, March 21, 2019, Morgantown, WV – poster presentation

December 3, 2018

MedChem Partners Sponsors Boston Pharmaceutical & BioScience Society Symposium

Boston, MA December 3-4 2018 – MedChem Partners sponsors the Boston Pharmaceutical & BioScience Society (Boston-PBSS) symposium titled “Fundamentals and Emerging Trends in Translational Research: Identifying Right Target, Right Drug, Right Dose and Right Patient”. This two day symposium features lectures from leading experts in the areas of fundamentals and emerging tools in translational research, translational strategies for immuno/ oncology, and rare diseases and oligonucleotide therapies; as well as two plenary lectures.

August 8, 2018

MedChem Partners Patent Allowed

Lexington, MA August 8, 2018 – United States Patent and Trademark Office (USPTO) has issued a Notice of Allowance for the U.S. patent application US 15/590,815 on which MedChem Partners Principle Steven Riesinger is a co-inventor . The patent, titled “Treatment of Cerebral Cavernous Malformations and Cerebral Aneurysms with Rho Kinase Inhibitors” (patent number US2017/0246181) discloses a series of Rho Kinase inhibitors. Rho kinase 2 (ROCK2) is a drug target that plays a key role in propagating biological signals that regulate brain endothelial cell barrier function and this enzyme is frequently overactivated in neurovascular pathologies where barrier function is compromised. In animal models of stroke, reversing the overactivation of ROCK2 that occurs in the vasculature restores endothelial cell barrier function.

June 20, 2018

MedChem Partners Sponsors New England Drug Discovery Discussion Group’s Summer Symposium

Waltham, MA June 20, 2018 – MedChem Partners sponsors New England Drug Discovery Discussion Group’s (NEDMDG) Summer Symposium. The mission of the NEDMDG is to provide a common forum for discussions about current topics in drug metabolism research among industry and academic scientists drawn from a wide range of disciplines.. The annual summer symposium, hosted at Astra Zeneca in Waltham , MA is a whole day event and includes a vendor exhibit, lectures, posters, time for interaction between scientists and lunch.

May 31, 2018

MedChem Partners Sponsors MALSI Day

Boston, MA May 31, 2018 – MedChem Partners sponsors the 11^th Massachusetts Life Sciences Innovation (MALSI) Day. MALSI Day is the biggest day for life sciences startups and innovation in the Commonwealth of Massachusetts. This is a high-energy, hands-on event which brings together scientific leaders and business experts to mingle with scientists, post-docs, professors, entrepreneurs, innovators, and venture capitalists.

The conference features keynotes, panels, innovators’ karketplace, networking reception with leading life sciences CEO’s, and poster competition. It is the flagship event of life sciences in Massachusetts, jointly and actively put together by all the major organizations that are involved in starting and supporting the life sciences start-up ecosystem in the Commonwealth.

http://www.mttc.org/malsi-2018/

May 26, 2018

MedChem Partners' Patent Allowed

Lexington, MA May 26, 2018 – World Intellectual property Organization (WIPO) has issued a Notice of Allowance for the PCT. patent application PCT/US2016/062526 on which MedChem Partners Principles Steven Riesinger and Tsvetelina Lazarova are co-inventors. The patent is titled “Methods for Improved Protection and Delivery of Aminothiols and Analogs Thereof” (patent number WO2017/087668). This application relates to improved methods of achieving protection of aminothiol), delivery of the protected compounds, and activation at desired sites in vivo. These novel compounds are useful for achieving improved therapeutic efficacy and lower toxicity of aminothiols, their metabolites, and analogs.

November 3, 2017

MedChem Partners' Poster at Diabetic Lower Extremities Symposium wins First Place.

Boston, MA Nov. 3, 2017 – MedChem Partners presents poster in collaboration with Dr. Dennis Orgill and colleagues from the Brigham and Women’s Hospital at the Diabetic Lower Extremeties Symposium (DLE) at Harvard Medical School. Diabetes is a major healthcare problem worldwide that is projected to grow exponentially in the following years. A common complication of diabetes is the development of persistent, non-healing foot wounds or diabetic foot ulcers (DFU), which pose a significant burden both financially as well as in quality of life issues. A simple and inexpensive treatment that could speed the time to recovery for DFU patients would greatly benefit the healthcare economic burden as well as patient comfort. Nitric oxide (NO) is a known signaling molecule which was found to improve wound healing if administrated externally. This poster details the results from a current study using a nitric oxide releasing compounds for the treatment of diabetic foot ulcers. Both in vitro and in vivo data is presented.

https://www.facebook.com/events/256367048118583/

The poster was awarded first place in the poster competition

October 12, 2017

MedChem Partners Sponsors Greater Boston Mass Spectrometry Society Discussion Group Corporate Night

Cambridge, MA Oct. 12, 2017 – MedChem Partners sponsors annual greater Boston mass spectrometry society Discussion Group (GBMSDG) corporate night. GBMSDG was created in 1985 as a platform to serve the mass spectrometry community by giving users a platform to exchange ideas, information, and research and development. The annual GBMSDG corporate night includes a vendor exhibit, time for interaction between scientists, dinner, and a plenary lecture.

June 1, 2017

MedChem Partners Sponsors MALSI Day

Boston, MA June 1, 2017 – MedChem Partners sponsors the 10th Massachusetts Life Sciences Innovation (MALSI) Day. MALSI Day is the biggest day for life sciences startups and innovation in the Commonwealth of Massachusetts. This is a high-energy, hands-on event which brings together scientific leaders and business experts to mingle with scientists, post-docs, professors, entrepreneurs, innovators, and venture capitalists.

The conference features Keynotes, Panels, Innovators’ Marketplace, Networking Reception with leading life sciences CEO’s, and Poster Competition. It is the flagship event of life sciences in Massachusetts, jointly and actively put together by all the major organizations that are involved in starting and supporting the life sciences start-up ecosystem in the Commonwealth.

http://www.mttc.org/malsi-2017/

March 1, 2017

MedChem Partners presents at Lunch and learn at Lab Central

Cambridge, MA March 1, 2017 – Steve Riesinger of MedChem Partners presents a seminar entitled “Early stage drug discovery of small molecules at a lunch and learn event at Lab Central. Lab Central is a first-of-its-kind shared laboratory space designed as a launchpad for high-potential life-sciences and biotech startups. It offers fully permitted laboratory and office space for as many as 60 startups comprising approximately 200 scientists and entrepreneurs.

http://www.labcentral.org

December 8, 2016

MedChem Partners announces sponsorship of MassBio CRO/CMO Symposium

Cambridge, MA Dec. 8, 2016 – MedChem Partners sponsors the 5th annual MassBio CRO/CMO Symposium. This event draws more than 300 attendees to discuss and evaluate the best practices that have evolved in shortening time to market. Through a series of panel discussions and breakout roundtables, strategies that have evolved in outsourcing and strategic partnerships in pre-clinical, clinical and manufacturing will be evaluated. In addition, the program will include keynotes, panel discussions, breakout/roundtable discussions and a well-trafficked Exhibit Hall, significant networking time (breaks and a closing reception) and, new this year, pre-conference workshops on finding a strategic partner and selling to pharma.

https://www.massbio.org/events/event-archive/2016-massbio-cro-cmo-symposium-1532

October, 2016

MedChem Partners sponsors Happy Hour event at MassChallenge

Boston, MA, October 2016 – MedChem Partners sponsors Happy Hour event at MassChallange Bostin Office. MassChallenge connects entrepreneurs with the resources they need to launch and succeed immediately. It is the largest-ever startup accelerator, and the first to support high-impact, early-stage entrepreneurs with no strings attached.

http://www.masschallenge.org

May 5, 2016

MedChem Partners Celebrates its 10 year anniversary.

Lexington, MA May 5^th 2016. MedChem Partners marks its 10^th year of service to the biotech, pharmaceutical and academic communities in Boston and beyond. We are grateful for the support that the local community has given us over the last 10 years and wish to thank everyone who has helped contribute to our success.

July 31, 2016

MedChem Partners presents Poster at Gordon Research Conference on Natural Products & Bioactive Compounds

Andover, NH July 31, 2016 – MedChem Partners’ Zina Ribkovskaia presents the poster titled: “Novel rapamycin analogs via ring contraction metathesis” at the Gordon conference on Natural Products & Bioactive Compounds. The poster details work performed at MedChem Partners on novel ring contraction chemistry performed on rapamycin transforming its 29 membered ring into a 27 membered ring. Using 28, 40-diacetate of rapamycin as a substrate and a ruthenium catalyst we successfully synthesized a new ring contracted rapamycin derivative. Structural proof of the contracted product was obtained by a series of 1D and 2D NMR experiments.

June 2, 2016

MedChem Partners Sponsors MALSI Day

Boston, MA June 2, 2016 – MedChem Partners sponsors the 9th Massachusetts Life Sciences Innovation (MALSI) Day. MALSI Day is the biggest day for life sciences startups and innovation in the Commonwealth of Massachusetts. This is a high-energy, hands-on event which brings together scientific and business leaders to mingle with scientists, post-docs, professors, entrepreneurs, innovators, and venture capitalists.

This year’s theme is: “The Life Sciences Center of the Universe – Making it Work for You”.

The conference featured Keynotes, Panels, Innovators’ Marketplace, Networking Reception with leading life sciences CEO’s, and Poster Competition. It was the flagship event of life sciences in Massachusetts, jointly and actively put together by all the major organizations that are involved in starting and supporting the life sciences start-up ecosystem in the Commonwealth.

http://www.mttc.org/archive-2016-massachusetts-life-sciences-innovation-day/

April 13, 2015

MedChem Partners Awarded Phase I SBIR Grant to Study Wound Healing

Lexington, MA April 13, 2015 – MedChem Partners in collaboration with Dr. Dennis Orgill of Brigham and Women’s hospital is awarded a Phase I SBIR grant titled “Drug containing hydrogels which release nitric oxide for diabetic wound healing” This grant is awarded to fund collaborative research into the wound healing properties of some novel nitric oxide releasing hydrogens which are under development at MedChem Partners. Dr. Orgill’s group at Brigham and Women’s Hospital are experts in diabetic wounds and wound healing in general. They will be performing test to assay the effectiveness of these novel compounds in promoting wound healing in vivo.

The goal of this grant is to discover and develop compounds which can release a therapeutically relevant amount of nitric oxide in a controllable manner, and demonstrate their ability to promote the healing of diabetic wounds in an in vivo model. To date, development of nitric oxide for these purposes has been hampered by the inability to stably sequester nitric oxide and release it in a controlled and selective way. Traditional treatment with gaseous nitric oxide is impractical due to the cumbersome high pressure gas tanks needed. The work undertaken in this project will: (i) identify novel compounds which stably sequester nitric oxide and only release it when they come in contact with a wound; (ii) identify the proper kinetics of release needed to deliver the appropriate does of nitric oxide to the wound and (iii) identify the structural requirements of compounds to achieve these kinetics in vivo. We will prepare several small libraries of compounds (36-45 analogs in total) which release nitric oxide at varying rates when exposed to plasma. These compounds will also be assayed for nitric oxide release and will be tested in a mouse model of diabetic wound healing

April 24, 2014

MedChem Partners Presents Start-Up Panel

Boston, MA April 24, 2014 MedChem partners presents a panel discussion titled “How to Start a Successful Biotech with Non-existent Capital” Starting a company is hard and takes a lot of perseverance: there are a lot of moving parts that all need to be coordinated. But an even more basic question is where do I find the parts, and how do I put them in motion….all with no money! Come hear from people who have been there before on topics such as how to find resources on a shoestring budget, what is a must have and where you can cut corners, how to negotiate contracts and licenses, and most importantly where to look for money. We have assembled a panel of seasoned entrepreneurs and professionals who have all “been there and done that” to provide insight into how to start a biotech with non-existent capital. We invite you to come and learn from the experts.

Moderator: Steven Riesinger, Ph.D., CEO and Co-Founder MedChem Partners

Panelists: Michael Cardone, Ph.D., CEO Eutropics Pharmaceuticals; Lauren Celano, Founder and CEO, Propel Careers; Marc Cote, COO Accelient Partners; Julio Vega, Partner Bingham McCutchen, LLP

Location: Bingham McCutchen LLP, Boston MA

– See more at: https://www.propelcareers.com/#/blog/post/20140417_1146_content.html

March 24, 2014

MedChem Partners Co-Founder to be on Early Stage Investment Panel

Boston on March 24, 2014 Tsvetelina Lazarova co-founder of MedChem Partners will be a panelist at the Redefining Early Stage Investments (RESI) conference – RESI is focused on connecting early stage life science companies with top-tier investors from the new and emerging investors in the space, including Family Offices, Venture Philanthropy, Mid-Level Private Equity, Virtual Pharmaceutical Companies, Angel Groups, Corporate Venture and Crowdfunding entities.

Life Science Nation’s RESI will feature 16 unique early stage investor panels that will provide the latest perspective on the state of investments in the industry, and provide a full day of partnering for companies looking to connect with service providers and investors. The investor panels are based on cutting-edge content derived from our research of industry investment activity. Additionally, RESI will also have a series of in-depth workshops in the areas of outbound fundraising, start-up valuation, and the legal landscape.

August 27, 2013

MedChem Partners awarded Phase I SBIR to study Alzheimer’s

Lexington, MA Aug. 27, 2013 – MedChem Partners in collaboration with Dr. Henry Querfurth of Brown University is awarded a Phase I SBIR grant titled “A Novel Insulin Pathway Agonist for Alzheimer’s Disease” to study novel treatments for Alzheimer’s disease. The funds will be used to study a novel small molecule drug which modulates the insulin pathway which is implicated in the onset and progression of Alzheimer’s disease. This represents a novel approach to this disease and may yield more promising results that the current therapies.

The SBIR grant will fund an expanded medicinal chemistry effort relying on structure guided approach to improve potency and improve the pharmacological profile of the lead series. In addition further profiling for effects on modulation of the insulin pathway in the brain will be undertaken along with functional in vivo teste to determine the effectiveness of this approach.

June 3, 2013

MedChem Partners to Sponsor MassChallenge

Lexington, MA, June 3, 2013– MedChem Partners was named as an in-kind sponsor for MassChallenge 2013. MassChallenge connects entrepreneurs with the resources they need to launch and succeed immediately. It is the largest-ever startup accelerator, and the first to support high-impact, early-stage entrepreneurs with no strings attached. “We are extremely pleased to be part of this fantastic organization. The support that exists for entrepreneurship and innovation here in Boston is one of the key drivers of the biotech industry here – it’s what makes Boston special and we are thrilled to be a part of it” says CEO Steven Riesinger. MedChem Partners will provide MassChallenge finalists mentorship and advice, and, as an in-kind sponsor will provide free or discounted consultation, lab space and drug discovery services.

May 20, 2013

MedChem Partners Co-founders Tsvetelina Lazarova and Steven Riesinger to Help the Mass Bio’s New Forums

Lexington, MA, May 20, 2013– Mass Bio has tapped the founders of MedChem Partners to help lead their forums. Steven Riesinger will be one of three co-Chairs of the drug discovery forum. The drug discovery forum is one of 9 new forums tasked with developing new content as well as shaping and executing programs at Mass Bio. Tsvetelina Lazarova was selected to become a Forum Advisory Board member where she and 17 other members will oversee all 9 of the forums and provide guidance and support while promoting interdisciplinary programming. See more at; http://www.bizjournals.com/boston/blog/bioflash/2013/05/massbio-taps-life-science-execs-to.html?page=all

December 10, 2012

MedChem Partners Announces the Opening of its Start-up Accelerator

Lexington, MA, Dec. 12, 2012– MedChem Partners established a new initiative today called Quick Start. Quick Start is a start-up accelerator which provides a turnkey laboratory solution for small companies and start-ups in need of chemistry space for short and medium term projects. Unlike most incubators, which are simply a small space with a short term lease, MedChem Partners Start-up Accelerator is a full service space designed to help launch a company. All equipment, common solvents, disposables and permitting are already in place…Accelerator members can move in and begin working immediately. In addition, MedChem Partners has built up a significant amount of expertise, experience and contacts in the drug discovery and chemistry R&D. Members of the Accelerator have free access to all MedChem Partners’ contacts and resources to help assemble a virtual team to drive the startup’s project to success.

Available resources Include:
24/7 access to facility
Hood, bench, and desk space
Access to instruments (removal, LC/MS, biotope, freezers lyophilize, etc…)
Use of MedChem Partners’ chemicals, solvents and consumables
Use of waste disposal services
Use of any MedChem Partners equipment
Use of wifi and computer network
Use of office supplies
Use of printers and scanners
Use of conference room
Use of MedChem Partners ordering system for supplies

November 22, 2012

MedChem Partners Visits University of Sofia and Sofia Tech Park in Bulgaria

Sofia, Bulgaria, Nov. 19, 2012– MedChem Partners announced today that it has been invited to visit The University of Sofia and Sofia Tech Park both in Sofia, Bulgaria to discuss the development of a biotech cluster there. Sofia University is the premiere science and technology university in Bulgaria and is seeking advice on the how best to use funding from the European Union for creation of a translation research center as well as development of its facilities and technology. Sofia Tech Park is Bulgaria’s first hi-tech R&D business park. This BGN 100 M facility will be fully completed in 2015 and will house high-tech and biotech companies. MedChem Partners has been in talks with both facilities to help grow the biotech presence in Bulgaria and take advantage of technology coming out of Bulgaria’s university system. In addition, MedChem Partners, University of Bulgaria, and Sofia Tech Park are working to expand the entrepreneurial environment in Bulgaria to try and capture the value of intellectual property being generated and turn that into commercially viable start-up companies. Key points of discussion included; establishing a start-up culture and feeding the entrepreneurial spirit which exists in Bulgaria.

September 12, 2012

MedChem Partners Announces It Has Expanded to China

Shanghai, China, Sept. 12, 2012– MedChem Partners announced today that it has signed an agreement with a partner in Shanghai China to provide access to a dedicated team of chemists in China. This team of scientists is retained to work exclusively on MedChem Partners projects and will help increase MedChem Partners efficiency and cost competitiveness. This new initiative will take the form of a hybrid model where the majority of the routine work is performed in China, but more involved or critical work is done in the US and seamlessly integrated with the work in China. This approach gives the best of both worlds: cost competitiveness of China with the quality control of the US and the ability to troubleshoot locally to solve problems rapidly. We anticipate that some projects will be too complicated or IP sensitive to send to China; those projects will be performed in our Lexington MA facility. Other projects may need to have significant oversight, but portions can be off-shored, and some projects may be able to be sent almost completely off-shore. The new hybrid chemistry model gives MedChem Partners the flexibility to adjust to the project needs rapidly to accommodate for cost, IP sensitivity, timing, or complexity

August 19, 2012

MedChem Partners Presents Poster at the 244th National meeting of the American Chemical Society in Philadelphia, PA

Lexington, MA, Aug. 19, 2012– MedChem Partners LLC presented a poster tiled “Novel Rapamycin Analogs via Metathesis” at the National Meeting of the American Chemical Society in Philadelphia, PA today. The meeting is the largest meeting of chemists in the world and attracted 13,313attendees. MedChem Partners has developed a novel metathesis contraction reaction that allows for the single step transformation of rapamycin to a new scaffold. In the process of validating the synthetic methodology, several novel rapamycin analogs were generated and their FKBP12 binding and half-life profiled. The research goal of retaining biological activity of the parent rapamycin, while demonstrating a shorter half-life than the parent compound was accomplished. The structure of the new rapamycin analogs was confirmed by high field 2D NMR experiments.

November 9, 2011

MedChem Partners LLC And Accendo Corporation Team Up To Offer Segmented Flow Chemistry

December 8, 2009

National Science Foundation awards MedChem Partners grant to develop novel chemistry for modification of natural products Medford, MA, Dec. 8, 2009– MedChem Partners LLC announced today the successful acquisition of funding from the National Science Foundation (NSF) to support the development of a broad based chemical technology for the modification of natural products. This phase I Small Business Innovation Research (SBIR) grant will be used to further the development of a novel single step chemical transformation that can be used to modify the structure of natural products economically and efficiently.

Natural products have long been a rich source of therapeutics and leads for the discovery of new drugs. Unfortunately, the complexity which makes these compounds attractive as potential drug candidates also makes their synthesis and derivatization quite challenging. Recently a variety of modern techniques have been described which allow the generation of semi-synthetic analogs under mild, selective conditions. MedChem Partners is developing several of these techniques for the direct modification of certain natural products. This technology allows for direct, one-pot modification of natural products and direct access to analogs, without the lengthy and expensive task of synthesizing the natural product from scratch. It will also alleviate the need for tedious protection/deprotection schemes as the current chemistry can function on unprotected natural products.

In addition MedChem Partners’ approach will allow for the direct modification of the core, or backbone, of the natural product. This chemistry will enable a generation of completely new and novel core structures which cannot currently be obtained by any other means. The end result is that new and novel molecules will become available which are patentable and which possess novel biological activity. This is a broad based chemical technology which can be applied across multiple therapeutic areas, and has the potential to speed up the discovery and production of novel biologically active compounds to serve as leads in the drug discovery pipeline.

December 8, 2009

National Science Foundation Awards MedChem Partners Grant to Develop Novel Chemistry for Modification of Natural Products

Medford, MA, Dec. 8, 2009– MedChem Partners LLC announced today the successful acquisition of funding from the National Science Foundation (NSF) to support the development of a broad based chemical technology for the modification of natural products. This phase I Small Business Innovation Research (SBIR) grant will be used to further the development of a novel single step chemical transformation that can be used to modify the structure of natural products economically and efficiently.