Biochemical profiling of anti-HIV prodrug Elsulfavirine (Elpida^®) and its active form VM1500A against a panel of twelve human carbonic anhydrase isoforms

2区 · 医学

ArticleOA

作者: Savchuk, Nikolay ; Krasavin, Mikhail ; Supuran, Claudiu T. ; Yakubova, Elena ; Nocentini, Alessio ; Kalinin, Stanislav

The non-nucleoside reverse transcriptase inhibitor VM1500A is approved for the treatment of HIV/AIDS in its N-acyl sulphonamide prodrug form elsulfavirine (Elpida^®). Biochemical profiling against twelve human carbonic anhydrase (CA, EC 4.2.1.1) isoforms showed that while elsulfavirine was a weak inhibitor of all isoforms, VM1500A potently and selectively inhibited human (h) hCA VII isoform, a proven target for the therapy of neuropathic pain. The latter is a common neurologic complication of HIV infection and we hypothesise that by using Elpida^® in patients may help alleviate this debilitating symptom.

2015-09-01·PHARMACEUTICAL CHEMISTRY JOURNAL

New Heterocyclic Hepatitis C Virus (HCV) Inhibitors Containing A 2-Aminomethyl-1H-Indole Fragment

作者: E. A. Bulanova ; A. A. Ivashchenko ; P. M. Yamanushkin ; O. D. Mit’kin ; E. V. Ezhova ; V. V. Bichko ; O. M. Korzinov ; A. V. Ivachtchenko

A focused library of heterocyclic compounds including a 2-aminomethyl-1H-benzimidazole, 2-aminomethylindole, benzofuran-2-ylmethylamine, or 2-piperazin-1-ylmethylbenzoxazole fragment was screened for the ability to inhibit in vitro hepatitis C virus (HCV).The synthetic methods were described.The antiviral activity and cytotoxicity data were presented.Most of the compounds carrying a benzoxazol-2-ylmethylamine fragment inhibited Huh7.3 human hepatoma cells infected in vitro with HCV with nanomolar potency but were inactive against the HCV RNA-replicon.The only exception was 9-methyl-N(6)-(3-nitrophenyl)-2,3,4,9-tetrahydro-1H-carbazole-1,6-diamine, which demonstrated nanomolar potency against HCV in both models.The most active and selective compounds were (piperazin-1-yl)-[(1H-indol-2-ylmethyl)piperidin-4-yl]-ketones (EC₅₀ 0.31-2.2 μM, CC₅₀ 10.2-110 μM) and 2-(1,2,3a,4,5,6-hexahydropyrazino[3,2,1-jk]carbazol-3-yl)acetamide (EC₅₀ 1.69±0.5 μM, CC₅₀ 114±42 μM).The two most selective inhibitors I (TI₅₀ = 52) and II (TI₅₀ = 68) were selected for further preclin. trials.

2015-02-01·Nature medicine1区 · 医学

Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance

1区 · 医学

Article

作者: Saltiel, Alan R ; Evans, Ronald M ; Perino, Alessia ; Schnabl, Bernd ; Coulter, Sally ; Schoonjans, Kristina ; Jacinto, Sandra ; Brenner, David A ; Fang, Sungsoon ; Yu, Elizabeth ; Lackey, Denise ; Suh, Jae Myoung ; Reilly, Shannon M ; Khvat, Alexander ; Yu, Ruth T ; Olefsky, Jerrold M ; Osborn, Olivia ; Lukasheva, Yelizaveta ; Liddle, Christopher ; Downes, Michael ; Yoshihara, Eiji ; Atkins, Annette R

The systemic expression of the bile acid (BA) sensor farnesoid X receptor (FXR) has led to promising new therapies targeting cholesterol metabolism, triglyceride production, hepatic steatosis and biliary cholestasis. In contrast to systemic therapy, bile acid release during a meal selectively activates intestinal FXR. By mimicking this tissue-selective effect, the gut-restricted FXR agonist fexaramine (Fex) robustly induces enteric fibroblast growth factor 15 (FGF15), leading to alterations in BA composition, but does so without activating FXR target genes in the liver. However, unlike systemic agonism, we find that Fex reduces diet-induced weight gain, body-wide inflammation and hepatic glucose production, while enhancing thermogenesis and browning of white adipose tissue (WAT). These pronounced metabolic improvements suggest tissue-restricted FXR activation as a new approach in the treatment of obesity and metabolic syndrome.

项与 ChemDiv, Inc. 相关的新闻（医药）

2024-05-13

·PRNewswire

ChemDiv to Participate in the EF Hutton Annual Global Conference, May 15, 2024

SAN DIEGO, May 13, 2024 /PRNewswire/ -- ChemDiv, Inc, announced today that Bill Farley, CEO, will participate in the EF Hutton Annual Global Conference (). The conference is being held in person at The Plaza Hotel, NY, NY 10019 on May 15, 2024. Bill Farley, CEO of ChemDiv, will provide corporate updates and highlights associated with ChemDiv's growth and development through partnerships with multiple venture backed accelerators, leveraging AI/LLM, chemical libraries, integrated biology and development with over 26 assets in the pipeline. These assets cover a broad range of therapeutic areas such as oncology, inflammation, CVMD, and anti-infectives. About ChemDiv Inc ChemDiv is a globally recognized leader in drug discovery solutions, offering fully integrated R&D services to support pharmaceutical projects. With over three decades of experience, ChemDiv delivers leads, drug candidates, and new drugs across various therapeutic areas to partners worldwide. For more information about ChemDiv visit . For media inquiries, please contact: Bill Farley CEO of ChemDiv [email protected] SOURCE ChemDiv

2024-01-03

·PRNewswire

ChemDiv Marks a Milestone as Orionis Biosciences' Novel Immunotherapy Enters Phase I Clinical Trials

SAN DIEGO, Jan. 3, 2024 /PRNewswire/ -- ChemDiv Inc, a leading provider of drug discovery platforms and development solutions, celebrates a significant milestone in collaboration with Orionis Biosciences: the commencement of Phase I clinical trials for ORB-011, a cutting-edge attenuated, cis-targeted interferon immunotherapy compound. ORB-011, a pioneering clinical candidate emerging from Orionis' innovative A-Kine® platform, is the culmination of rigorous research and development efforts facilitated by ChemDiv's robust covalent and bifunctional chem-bio arsenal. Engineered to exhibit highly selective, targeted activation of tumor-antigen-presenting cDC1 dendritic cells, ORB-011 leverages ChemDiv's expertise in warheads to optimize interferon's therapeutic potential while mitigating broad systemic activity and associated toxicities characteristic of traditional cytokine therapies. "We take immense pride in our support of Orionis Biosciences' discovery and development, which has culminated in the advancement of ORB-011 into clinical trials," said ChemDiv's CEO, Bill Farley. "This marks a significant step in harnessing intrinsic immunobiology pharmacologically, and we are excited about the potential impact it may have on revolutionizing cancer therapeutics." The initiation of Phase I clinical trials for ORB-011 is a significant milestone, underscoring the transformative potential of ChemDiv and Orionis Biosciences synergistic research, pushing the boundaries of collaborative drug discovery to improve patient outcomes in the fight against cancer. About ChemDiv Inc: ChemDiv is a globally recognized leader in drug discovery solutions, offering fully integrated R&D services to support pharmaceutical projects. With over three decades of experience, ChemDiv delivers leads, drug candidates, and new drugs across various therapeutic areas to partners worldwide. For more information about ChemDiv visit . For media inquiries, please contact: Bill Farley CEO of ChemDiv [email protected] SOURCE ChemDiv

免疫疗法临床1期

2023-12-28

·PRNewswire

ChemDiv Forges Strategic Partnership with The University of Texas Medical Branch (UTMB) to Expand Its High-throughput Screening Research Capabilities

SAN DIEGO, Dec. 28, 2023 /PRNewswire/ -- ChemDiv, a global leader in drug discovery solutions, announces a strategic collaboration with the University of Texas Medical Branch (UTMB) to facilitate the expansion of its inventory and advance the institution's High-throughput Screening (HTS) research programs. ChemDiv's comprehensive suite of fully integrated Research & Development services offers UTMB unparalleled support in its pursuit of groundbreaking medical research. By leveraging ChemDiv's 32 years of experience, advanced capabilities, and a seasoned team of experts, UTMB aims to push the boundaries of medical research and translate discoveries into tangible treatments for pressing medical needs. "At ChemDiv, we are dedicated to catalyzing pioneering research, and our collaboration with UTMB exemplifies our commitment to advancing healthcare globally," said Bill Farley, CEO of ChemDiv. "Our team's expertise and cutting-edge resources are poised to significantly augment UTMB's HTS research center, accelerating the discovery of novel therapeutic solutions." About ChemDiv: ChemDiv is dedicated to partnering in discovery and development of breakthrough therapies based on its unique chem-bio platforms: molecular glues, stabilizers and degraders; covalent and non-covalent binders; bifunctional molecules for synergistic effect and synthetic lethality. Over the past 32 years ChemDiv has successfully completed hundreds of lead, candidate and new drug programs to treat cancer, neurological, infectious, cardiometabolic and immune diseases with pharma, biotech and academic partners around the globe. For more information about ChemDiv, visit . For further information, please contact: Bill Farley CEO of ChemDiv Bfarley@chemdiv.com SOURCE ChemDiv

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