A PHASE IIb RANDOMIZED, CONTROLLED, PARTIALLY BLINDED CLINICAL TRIAL TO INVESTIGATE SAFETY, EFFICACY AND DOSE-RESPONSE OF BMS-986001 IN TREATMENT-NAÏVE HIV-1-INFECTED SUBJECTS, FOLLOWED BY AN OPEN-LABEL PERIOD ON THE RECOMMENDED DOSE.

开始日期-

申办/合作机构

Bristol Myers Squibb Co.

NCT01489046 / Terminated临床2期

A Phase IIb Randomized, Controlled, Partially Blinded Clinical Trial to Investigate Safety, Efficacy and Dose-response of BMS-986001 in Treatment-naive HIV-1-infected Subjects, Followed by an Open-label Period on the Recommended Dose

The purpose of this study is to identify at least one dose of BMS-986001 which is safe, well tolerated, and efficacious when combined with Efavirenz (EFV) + Lamivudine (3TC) for treatment-naive Human Immunodeficiency Virus 1 (HIV-1) infected subjects

开始日期2011-02-01

申办/合作机构

Bristol Myers Squibb Co.

100 项与 Censavudine 相关的临床结果

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100 项与 Censavudine 相关的转化医学

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100 项与 Censavudine 相关的专利（医药）

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项与 Censavudine 相关的文献（医药）

2024-09-01·Bioorganic & Medicinal Chemistry

Current status of the small molecule anti-HIV drugs in the pipeline or recently approved

Review

作者: Habarurema, Gratien ; Twizeyimana, Eric ; Gahamanyi, Noël ; Claude Tomani, Jean ; Ishimwe, Nestor ; Olawode, Emmanuel Oladayo ; Uyisenga, Jeanne Primitive ; Umumararungu, Théoneste ; Katandula, Jonathan ; Saeed, Shamsaldeen Ibrahim ; Nyandwi, Jean Baptiste ; Mpenda, Matabishi

Human Immunodeficiency Virus (HIV) is the causative agent of Acquired Immunodeficiency Syndrome (AIDS) with high morbidity and mortality rates. Treatment of AIDS/HIV is being complicated by increasing resistance to currently used antiretroviral (ARV) drugs, mainly in low- and middle-income countries (LMICs) due to drug misuse, poor drug supply and poor treatment monitoring. However, progress has been made in the development of new ARV drugs, targeting different HIV components (Fig. 1). This review aims at presenting and discussing the progress made towards the discovery of new ARVs that are at different stages of clinical trials as of July 2024. For each compound, the mechanism of action, target biomolecule, genes associated with resistance, efficacy and safety, class, and phase of clinical trial are discussed. These compounds include analogues of nucleoside reverse transcriptase inhibitors (NRTIs) - islatravir and censavudine; non-nucleoside reverse transcriptase inhibitors (NNRTIs) - Rilpivirine, elsulfavirine and doravirine; integrase inhibitors namely cabotegravir and dolutegravir and chemokine coreceptors 5 and 2 (CC5/CCR2) antagonists for example cenicriviroc. Also, fostemsavir is being developed as an attachment inhibitor while lenacapavir, VH4004280 and VH4011499 are capsid inhibitors. Others are maturation inhibitors such as GSK-254, GSK3532795, GSK3739937, GSK2838232, and other compounds labelled as miscellaneous (do not belong to the classical groups of anti-HIV drugs or to the newer classes) such as obefazimod and BIT225. There is a considerable progress in the development of new anti-HIV drugs and the effort will continue since HIV infections has no cure or vaccine till now. Efforts are needed to reduce the toxicity of available drugs or discover new drugs with new classes which can delay the development of resistance.

2022-04-01·Journal of Labelled Compounds and Radiopharmaceuticals4区 · 医学

Synthesis of carbon‐14 and stable isotope labeled Censavudine

4区 · 医学

Article

作者: Shi, Zhongping ; Burrell, Richard C. ; Ortiz, Adrian ; Bonacorsi, Samuel J. ; Benkovics, Tamas

Censavudine is a nucleoside reverse transcriptase inhibitor (NRTI) explored clinically by Bristol Myers Squibb for the treatment of human immunodeficiency virus‐1 (HIV‐1). As part of the development process, a carbon‐14 labeled analog was synthesized for use in a human absorption, distribution, metabolism, and excretion (ADME) study. A stable isotope labeled analog was also synthesized for use as a mass spectrum internal standard in bioanalytical assays to accurately quantify the concentration of the drug in biological samples. Carbon‐14 labeled Censavudine was synthesized in 10 steps in a 9% overall yield from carbon‐14 labeled trimethylsilylacetylene. A total of 4.44 mCi of material was prepared with a specific activity of 0.25 μCi/mg. The radiochemical and UV purities were 99% and it met all of the specifications for use in a human clinical study. Deuterium labeled Censavudine was synthesized in two steps in a 68% overall yield from [D4]‐thymine. A total of 237 mg were prepared with a UV purity of 99%.

2022-02-15·Accounts of Chemical Research1区 · 化学

4′-Modified Nucleosides for Antiviral Drug Discovery: Achievements and Perspectives

1区 · 化学

Article

作者: Chang, Junbiao

Modified nucleosides show therapeutic promise for antiviral therapies. However, issues including the emergence of drug resistance, toxicity, and coinfections have posed new challenges for nucleoside-based antiviral drug discovery, particularly in the era of the coronavirus disease 2019 (COVID-19) pandemic. Chemical manipulation could impact the antiviral potency, safety, and drug resistance of nucleosides. Generally, modified nucleosides are difficult to recognize by intracellular important enzymes as substrates and thus exhibit low toxicity. 4'-Modified nucleosides represent an important subclass of modified nucleosides for antiviral therapies. To prevent the occurrence of drug resistance, 4'-modified nucleosides should have 3'-OH, which should also be chemically unreactive for proviral DNA biosynthesis. The absence of 3'-OH may explain the occurrence of drug resistance for censavudine. The introduction of 4'-substituents improves enzymatic and acidic stability and makes the nucleosides more lipophilic, thus improving cell permeability and bioavailability. Steric hindrance between the 4'-substituent and 3'-OH changes the furanose conformation to the 3'-endo type, in which the oxygen lone pair on the furanose ring could not form an oxocarbonium ion for glycolysis. Currently, seven 4'-modified nucleoside drug candidates such as azvudine (also known as FNC), islatravir, censavudine, balapiravir, lumicitabine, AL-335, and 4-azidothymidine have progressed into clinical stages for treating viral infections. Of note, FNC was officially approved by NMPA in July 2021 for use in adult patients with high HIV-1 virus loads (nos. H20210035 and H20210036), providing an alternative therapeutic for patients with HIV-1. The long-term cellular retention of FNC suggests its potential as a long-lasting pre-exposure prophylaxis (PrEP) agent for preventing HIV-1 infection. Mechanistically, FNC not only inhibited HIV-1 reverse transcription and replication but also restored A3G expression in peripheral blood CD4⁺ T cells in HIV-1 patients receiving FNC. The 4'-azido group in azvudine stabilizes the 3'-C-endo (north) conformation by steric effects and the formation of an intramolecular hydrogen bond with the 3'-OH group, thus decreasing the nucleophilicity of 3'-OH. The north conformation may also enhance the phosphorylation efficiency of FNC by cellular kinases. Encouragingly, FNC, islatravir, and balapiravir show promise for the treatment of coronaviruses, of which FNC has advanced to phase 3 clinical trials in different countries to treat patients with COVID-19 (clinical trial numbers: NCT04668235 and NCT04425772). FNC cured the COVID-19 disease in almost all patients and showed better therapeutic efficacy than remdesivir. In this Account, we provide an overview of 4'-modified nucleoside analogs in clinical stages for antiviral therapies, highlighting the drug discovery strategies, structure-activity relationship studies, and preclinical/clinical studies and also give our perspectives on nucleoside-based antiviral drug discovery.

项与 Censavudine 相关的新闻（医药）

2023-09-14

·Pharmaceutical Technology

First Wave plans to repurpose Sanofi’s capeserod as GI therapy

Phalguni Deswal @Phalguni_GD Capeserod is a selective partial agonist of the serotonin type 4 (5-HT4) receptor. Image Credit: Keitma / Shutterstock. First Wave BioPharma has acquired Sanofi’s capeserod with plans to repurpose it as a gastrointestinal (GI) disease therapy. Following the news , First Wave’s stock skyrocketed by over 80% in pre-market trading. The US-based company has a market cap of $3.112m. Recommended Reports Reports LOA and PTSR Model - Buntanetap Tartrate in Frontotemporal Dementia (FTD) GlobalData Reports LOA and PTSR Model - Censavudine in Frontotemporal Dementia (FTD) GlobalData View all The agreement includes a $500,000 upfront payment, with developmental and commercial milestone payments of up to $46m and $235m, respectively. Additionally, Sanofi would have the right of first refusal on any capeserod sublicensing agreement and would be entitled to a percentage of any licensing payments. Sanofi also reserves the first refusal right to reacquire capeserod during development. Capeserod is a selective partial agonist of the serotonin type 4 (5-HT4) receptor. In the GI tract , these receptors perform various functions, including gastric emptying, decreasing oesophageal reflux, and promoting intestinal peristalsis. Sanofi had previously evaluated capeserod in Alzheimer’s disease and urinary incontinence but had since terminated the drug development. However, Fist Wave analysis of the drug had identified its potential application in several GI disorders. First Wave plans to meet with the US Food and Drug Administration (FDA) to ascertain a developmental and regulatory pathway for capeserod and plans to initiate clinical trials in 2024. First Wave CEO James Sapirstein said: “Capeserod has been investigated in multiple clinical trials involving over 600 patients and through this research and AI-based analyses evidence emerged suggesting the drug possesses a unique mechanism of action that is applicable to several GI indications underserved by currently available therapeutics. “We intend to immediately initiate discussions with the FDA focused on a development and regulatory plan that would enable us to begin Phase II clinical trials of capeserod in 2024.” In June, Sanofi partnered with BioMed X to research an artificial intelligence (AI)-driven drug discovery platform .

引进/卖出并购临床2期

100 项与 Censavudine 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10550	Censavudine	-	DB12074

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
阿尔茨海默症	临床2期	日本	Transposon Therapeutics, Inc.初创企业	2020-07-13
Aicardi-Goutieres综合征	临床2期	-	Oncolys BioPharma, Inc.	-
肌萎缩侧索硬化	临床2期	-	Oncolys BioPharma, Inc.	-
额颞痴呆	临床2期	-	Oncolys BioPharma, Inc.	-
进行性核上性麻痹	临床2期	-	Oncolys BioPharma, Inc.	-
HIV感染	临床前	波兰	Oncolys BioPharma, Inc.	-
HIV感染	临床前	德国	Oncolys BioPharma, Inc.	-