BMS-955176(BMS-955176) - 在研适应症：HIV感染_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点-

作用机制

HIV复制抑制剂、病毒复制抑制剂

治疗领域

免疫系统疾病感染泌尿生殖系统疾病

在研适应症

HIV感染

非在研适应症-

原研机构

Bristol Myers Squibb Co.

在研机构

Bristol Myers Squibb Co.

非在研机构

GSK Plc

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C42H62N2O4S

InChIKeyXDMUFNNPLXHNKA-ZTESCHFWSA-N

CAS号1392312-45-6

关联

11

项与 BMS-955176 相关的临床试验

NCT02715479 / Completed临床1期

A Two-way Drug Interaction Study to Evaluate the Effect of BMS-955176 on the Pharmacokinetics of Dolutegravir and the Effect of Dolutegravir on the Pharmacokinetics of BMS-955176

The purpose of this study is to evaluate how BMS955176 affects pharmacokinetics (PK) of Dolutegravir (DTG) and also how DTG administration affects the PK of BMS955176

开始日期2016-04-01

申办/合作机构

ViiV Healthcare Ltd.

[+1]

NCT02608918 / Completed临床1期

An Open-Label Taste Assessment of BMS-955176 in Healthy Subjects

The purpose of the study is to assess the taste properties of HIV inhibitor

开始日期2016-01-05

申办/合作机构

ViiV Healthcare Ltd.

[+1]

NCT02578277 / Completed临床1期

Effects of BMS-955176 on the Single-dose Pharmacokinetics of Probe Substrates (Caffeine, Metoprolol, Montelukast, Flurbiprofen, Omeprazole, Midazolam, Digoxin, and Pravastatin) in Healthy Subjects

The purpose of the study is to study the effects of BMS-955176 on the single-dose PK parameters of probe substrates caffeine, metoprolol, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin

开始日期2015-11-09

申办/合作机构

ViiV Healthcare Ltd.

100 项与 BMS-955176 相关的临床结果

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100 项与 BMS-955176 相关的转化医学

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100 项与 BMS-955176 相关的专利（医药）

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15

项与 BMS-955176 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 ; Katandula, Jonathan ; Umumararungu, Théoneste ; 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.

2022-09-22·Journal of Medicinal Chemistry1区 · 医学

The Discovery of GSK3640254, a Next-Generation Inhibitor of HIV-1 Maturation

1区 · 医学

Article

作者: Hartz, Richard A. ; Hanumegowda, Umesh ; Benitex, Yulia ; Dicker, Ira ; Regueiro-Ren, Alicia ; Rahematpura, Sandhya ; Wu, Dauh-Rurng ; Protack, Tricia ; Hou, Xiaoping ; Mathur, Arvind ; Liu, Zheng ; Phillips, Thomas ; Park, Hyunsoo ; Zhang, Sharon ; Chen, Jie ; Sarjeant, Amy ; Santone, Kenneth S. ; Parker, Dawn ; Venables, Brian L. ; Kempson, James ; Rampulla, Richard ; Gupta, Anuradha ; Meanwell, Nicholas A. ; Li, Peng ; Li, Zhufang ; Swidorski, Jacob J. ; Chen, Yan ; Lin, Zeyu ; Jenkins, Susan ; Haskell, Roy ; Krystal, Mark ; Sin, Ny ; Sit, Sing-Yuen ; Cockett, Mark

GSK3640254 is an HIV-1 maturation inhibitor (MI) that exhibits significantly improved antiviral activity toward a range of clinically relevant polymorphic variants with reduced sensitivity toward the second-generation MI GSK3532795 (BMS-955176). The key structural difference between GSK3640254 and its predecessor is the replacement of the para-substituted benzoic acid moiety attached at the C-3 position of the triterpenoid core with a cyclohex-3-ene-1-carboxylic acid substituted with a CH₂F moiety at the carbon atom α- to the pharmacophoric carboxylic acid. This structural element provided a new vector with which to explore structure-activity relationships (SARs) and led to compounds with improved polymorphic coverage while preserving pharmacokinetic (PK) properties. The approach to the design of GSK3640254, the development of a synthetic route and its preclinical profile are discussed. GSK3640254 is currently in phase IIb clinical trials after demonstrating a dose-related reduction in HIV-1 viral load over 7-10 days of dosing to HIV-1-infected subjects.

2021-03-01·Bioorganic & Medicinal Chemistry Letters4区 · 医学

Design and exploration of C-3 benzoic acid bioisosteres and alkyl replacements in the context of GSK3532795 (BMS-955176) that exhibit broad spectrum HIV-1 maturation inhibition

4区 · 医学

Article

作者: Dicker, Ira B ; Jenkins, Susan ; Beno, Brett R ; Parker, Dawn D ; Ng, Alicia ; Hanumegowda, Umesh ; Gupta, Anuradha ; Protack, Tricia ; Meanwell, Nicholas A ; Shanmugam, Yoganand ; Swidorski, Jacob J ; Regueiro-Ren, Alicia ; Krystal, Mark

GSK3532795 (formerly BMS-955176) is a second-generation HIV-1 maturation inhibitor that has shown broad spectrum antiviral activity and preclinical PK predictive of once-daily dosing in humans. Although efficacy was confirmed in clinical trials, the observation of gastrointestinal intolerability and the emergence of drug resistant virus in a Phase 2b clinical study led to the discontinuation of GSK3532795. As part of the effort to further map the maturation inhibitor pharmacophore and provide additional structural options, the evaluation of alternates to the C-3 phenyl substituent in this chemotype was pursued. A cyclohexene carboxylic acid provided exceptional inhibition of wild-type, V370A and ΔV370 mutant viruses in addition to a suitable PK profile following oral dosing to rats. In addition, a novel spiro[3.3]hept-5-ene was designed to extend the carboxylic acid further from the triterpenoid core while reducing side chain flexibility compared to the other alkyl substituents. This modification was shown to closely emulate the C-3 benzoic acid moiety of GSK3532795 from both a potency and PK perspective, providing a non-traditional, sp³-rich bioisostere of benzene. Herein, we detail additional modifications to the C-3 position of the triterpenoid core that offer effective replacements for the benzoic acid of GSK3532795 and capture the interplay between these new C-3 elements and C-17 modifications that contribute to enhanced polymorph coverage.

100 项与 BMS-955176 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	BMS-955176	-	DB15193

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
HIV感染	临床2期	西班牙	GSK Plc	2015-05-12
HIV感染	临床2期	德国	GSK Plc	2015-05-12
HIV感染	临床2期	加拿大	GSK Plc	2015-05-12
HIV感染	临床2期	南非	GSK Plc	2015-05-12
HIV感染	临床2期	墨西哥	GSK Plc	2015-05-12
HIV感染	临床2期	意大利	GSK Plc	2015-05-12
HIV感染	临床2期	美国	GSK Plc	2015-05-12
HIV感染	临床2期	英国	GSK Plc	2015-05-12
HIV感染	临床2期	智利	GSK Plc	2015-05-12
HIV感染	临床2期	阿根廷	GSK Plc	2015-05-12

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02415595 (Pubmed \| J Biol Chem) 人工标引	临床2期	HIV感染一线	206	tenofovir disoproxil fumarate+emtricitabine+GSK3532795	夢鑰鏇艱顧鬱鏇蓋網膚(衊觸壓襯鏇網鏇願壓廠) = 製獵糧蓋艱襯衊構積遞淵窪範鬱遞鏇構構觸淵 (鏇窪範觸鹽憲鹽鹹膚鹹 ) 更多	不佳	2018-10-23
				tenofovir disoproxil fumarate+emtricitabine+efavirenz	夢鑰鏇艱顧鬱鏇蓋網膚(衊觸壓襯鏇網鏇願壓廠) = 積淵膚網鑰膚蓋鬱鏇膚淵窪範鬱遞鏇構構觸淵 (鏇窪範觸鹽憲鹽鹹膚鹹 ) 更多
NCT02415595 (CTgov)	临床2期	HIV感染	210	FTC+TDF+BMS-955176 (BMS-955176/GSK3532795 60 mg + TDF/FTC)	壓壓範淵顧繭壓壓憲蓋(窪鏇醖廠選憲壓願獵膚) = 簾構遞選蓋鑰製鏇衊遞襯鬱壓範壓糧鏇願獵廠 (艱製艱醖壓齋衊願膚獵, 網憲範簾築遞選艱憲網 ~ 獵範積網鬱鑰鹽夢網鬱) 更多	-	2018-09-19
				FTC+TDF+BMS-955176 (BMS-955176/GSK3532795 120 mg + TDF/FTC)	壓壓範淵顧繭壓壓憲蓋(窪鏇醖廠選憲壓願獵膚) = 獵醖淵鹹鹽餘選構鹹餘襯鬱壓範壓糧鏇願獵廠 (艱製艱醖壓齋衊願膚獵, 膚艱鬱餘鑰餘築遞網鏇 ~ 壓網齋衊鑰選鏇鏇選鑰) 更多
NCT02386098 (CTgov)	临床2期	HIV感染	86	DTG+BMS-955176+ATV/r (Stage 1: BMS-955176 120 mg QD+ATV/r 300/100 mg QD+DTG 50 mg QD)	獵齋艱窪壓範鬱製衊願(觸觸鹽齋簾齋窪艱膚鏇) = 艱憲襯膚廠鏇簾廠鹽獵願膚醖遞衊鹹顧糧糧淵 (蓋鬱憲獵鑰餘鏇顧夢淵, 蓋膚齋獵鏇鹹築壓願簾 ~ 選壓壓簾鑰觸製夢獵醖) 更多	-	2018-08-20
				DTG+TDF+ATV/r (Stage 1: TDF 300 mg QD+ATV/r 300/100 mg QD+DTG 50 mg QD)	獵齋艱窪壓範鬱製衊願(觸觸鹽齋簾齋窪艱膚鏇) = 膚簾餘膚鏇壓鑰製鹹窪願膚醖遞衊鹹顧糧糧淵 (蓋鬱憲獵鑰餘鏇顧夢淵, 窪鏇遞壓選鏇鹹顧網憲 ~ 膚願鹹製膚簾廠衊築餘) 更多
NCT01803074 (AI468002, Pubmed \| Clin Infect Dis)	临床2期	HIV感染	107	GSK3532795	網鑰醖鏇齋顧獵鹽壓艱(壓蓋築齋觸鬱築窪顧壓) = 膚夢壓鏇壓衊襯鹹選簾鹽鏇壓網願築觸遞窪鏇 (簾繭顧築願蓋鹹醖簾壓 )	-	2017-08-01
AI468038 (205891) (IAS2017)	N/A	HIV感染	210	GSK3532795 60 mg + TDF/FTC QD	鬱鹽淵醖構觸廠襯蓋淵(壓壓廠鬱醖獵鏇築鹽製) = 鬱顧獵網艱鹹窪廠顧範簾衊顧憲衊糧積繭製鑰 (範網積繭鹹蓋糧窪範窪 ) 更多	-	2017-01-01
				GSK3532795 120 mg + TDF/FTC QD	鬱鹽淵醖構觸廠襯蓋淵(壓壓廠鬱醖獵鏇築鹽製) = 淵築顧夢淵範衊衊壓繭簾衊顧憲衊糧積繭製鑰 (範網積繭鹹蓋糧窪範窪 ) 更多
IAS2015	N/A	HIV感染	-	BMS-955176	遞壓遞鹽範繭鏇齋艱廠(獵選蓋積築選鬱鑰齋製) = 齋鹹範範鏇願窪鹽觸膚鹹構糧繭襯憲廠衊鏇窪 (衊顧鬱衊餘鑰衊憲窪簾, 3.4) 更多	-	2015-01-01