贝韦立马(Bevirimat Dimeglumine) - 药物靶点：HIV-1 capsid_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Bevirimat、Bevirimat dimeglumine (USAN)

+ [11]

靶点

HIV-1 capsid

作用机制

HIV-1 capsid抑制剂(HIV-1衣壳蛋白抑制剂)

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-

非在研适应症

HIV感染HIV血清阳性

原研机构

Myrexis, Inc.

在研机构-

非在研机构

Myrexis, Inc.

最高研发阶段终止临床2期

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C36H56O6

InChIKeyYJEJKUQEXFSVCJ-WRFMNRASSA-N

CAS号174022-42-5

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关联

5

项与贝韦立马相关的临床试验

NCT01026727 / Terminated临床2期

A Phase 2b Multicenter, Randomized, Open Label, Comparative Trial of MPC-4326 in Combination With a Two to Three Drug Optimized Background Regimen Versus an Optimized, Three to Four Drug Antiretroviral Regimen for the Treatment of Triple Class Antiretroviral Experienced, HIV-1 Infected Subjects Failing Current Therapy

This phase 2b study is designed to assess the long-term efficacy (24 weeks) of MPC-4326 in combination with a 2-3 drug optimized background regimen (OBR) relative to the efficacy of a 3-4 antiretroviral (ARV) regimen in treatment experienced, HIV-1 infected subjects.

开始日期2009-11-01

申办/合作机构

Myrexis, Inc.

NCT01097070 / Completed临床2期

A Phase II Multicenter, Open-label, Randomized, Parrallel Group Study to Assess the Pharmacokinetics of Bevirimat (BVM) 100 mg Tablets Administered to HIV-1 Positive Patients for 15 Days

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (behavior in the body) of bevirimat administered for 15 days to HIV-positive individuals.

开始日期2008-11-01

申办/合作机构

Myrexis, Inc.

NCT00967187 / Completed临床2期

A Phase II Multicenter, Open-label, Randomized, Parallel Group, Study of Bevirimat in HIV-1 Positive Patients to Evaluate the Safety, Efficacy, and Pharmacokinetics of MPC-4326 Administered as Monotherapy for 14 Days and as Part of an Optimized Background Regimen for up to 72 Weeks.

To evaluate the antiretroviral activity and safety of 200 mg BID and 300 mg BID doses of MPC-4326 administered as monotherapy for 14 days to HIV-1 positive patients. Patients with an initial treatment response will have the option to continue MPC-4326 in combination with an Optimized Backround Regimen for a maximum of 72 weeks.

开始日期2008-05-01

申办/合作机构

Myrexis, Inc.

100 项与贝韦立马相关的临床结果

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100 项与贝韦立马相关的转化医学

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100 项与贝韦立马相关的专利（医药）

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92

项与贝韦立马相关的文献（医药）

2021-11-17·Journal of the American Chemical Society1区 · 化学

Preservation of HIV-1 Gag Helical Bundle Symmetry by Bevirimat Is Central to Maturation Inhibition

1区 · 化学

Article

作者: Pak, Alexander J. ; Yeager, Mark ; Purdy, Michael D. ; Voth, Gregory A.

The assembly and maturation of human immunodeficiency virus type 1 (HIV-1) require proteolytic cleavage of the Gag polyprotein. The rate-limiting step resides at the junction between the capsid protein CA and spacer peptide 1, which assembles as a six-helix bundle (6HB). Bevirimat (BVM), the first-in-class maturation inhibitor drug, targets the 6HB and impedes proteolytic cleavage, yet the molecular mechanisms of its activity, and relatedly, the escape mechanisms of mutant viruses, remain unclear. Here, we employed extensive molecular dynamics (MD) simulations and free energy calculations to quantitatively investigate molecular structure-activity relationships, comparing wild-type and mutant viruses in the presence and absence of BVM and inositol hexakisphosphate (IP6), an assembly cofactor. Our analysis shows that the efficacy of BVM is directly correlated with preservation of 6-fold symmetry in the 6HB, which exists as an ensemble of structural states. We identified two primary escape mechanisms, and both lead to loss of symmetry, thereby facilitating helix uncoiling to aid access of protease. Our findings also highlight specific interactions that can be targeted for improved inhibitor activity and support the use of MD simulations for future inhibitor design.

2021-05-29·Advances in Virology

Natural Products with Inhibitory Activity against Human Immunodeficiency Virus Type 1

Review

作者: Ramírez, Katherin ; Orozco, Lina P. ; Zapata, Wildeman ; Florez-Sampedro, Laura ; Serna-Arbeláez, Maria S. ; Galeano, Elkin

Infections caused by human immunodeficiency virus (HIV) are considered one of the main public health problems worldwide. Antiretroviral therapy (ART) is the current modality of treatment for HIV-1 infection. It comprises the combined use of several drugs and can decrease the viral load and increase the CD4+ T cell count in patients with HIV-1 infection, thereby proving to be an effective modality. This therapy significantly decreases the rate of morbidity and mortality owing to acquired immunodeficiency syndrome (AIDS) and prolongs and improves the quality of life of infected patients. However, nonadherence to ART may increase viral resistance to antiretroviral drugs and transmission of drug-resistant strains of HIV. Therefore, it is necessary to continue research for compounds with anti-HIV-1 activity, exhibiting a potential for the development of an alternative or complementary therapy to ART with low cost and fewer side effects. Natural products and their derivatives represent an excellent option owing to their therapeutic potential against HIV. Currently, the derivatives of natural products available as anti-HIV-1 agents include zidovudine, an arabinonucleoside derivative of the Caribbean marine sponge (Tectitethya crypta), which inhibits the reverse transcriptase of the virus. This was the first antiviral agent approved for treatment of HIV infection. Additionally, bevirimat (isolated from Syzygium claviflorum) and calanolide A (isolated from Calophyllum sp.) are inhibitors of viral maturation and reverse transcription process, respectively. In the present review, we aimed to describe the wide repertoire of natural compounds exhibiting anti-HIV-1 activity that can be considered for designing new therapeutic strategies to curb the HIV pandemic.

2021-04-01·European Journal of Medicinal Chemistry1区 · 医学

Design, synthesis, and structure activity relationship analysis of new betulinic acid derivatives as potent HIV inhibitors

1区 · 医学

Article

作者: Yu Zhao ; Kuo-Hsiung Lee ; Chin-Ho Chen ; Susan L. Morris-Natschke

Prior modification of betulinic acid (1), a natural product lead with promising anti-HIV activity, produced 3-O-(3',3'-dimethylsuccinyl)betulinic acid (bevirimat, 3), the first-in-class HIV maturation inhibitor. After 3-resistant variants were found during Phase I and IIa clinical trials, further modification of 3 produced 4 with improved activity against wild-type and 3-resistant HIV-1. In continued efforts to optimize 1, 63 final products have now been designed, synthesized, and evaluated for anti-HIV-1 replication activity against HIV-1_NL4-3 infected MT-4 cell lines. Five known and 21 new derivatives were as or more potent than 3 (EC₅₀ 0.065 μM), while eight new derivatives were as or more potent than 4 (EC₅₀ 0.019 μM). These derivatives feature expanded structural diversity and chemical space that may improve the antiviral activity and address the growing resistance crisis. Structure-Activity Relationship (SAR) correlations were thoroughly analyzed, and a 3D Quantitative SAR model with high predictability was constructed to facilitate further rational design and development of new potent derivatives.

100 项与贝韦立马相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D06564	贝韦立马	-	DB06581

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
HIV血清阳性	临床2期	澳大利亚	Myrexis, Inc.	2008-05-01
HIV感染	临床2期	美国	Myrexis, Inc.	2006-04-01

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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


IAS2011	N/A	HIV感染	-	Bevirimat	齋構憲繭鑰鬱壓願遞淵(鹽顧構衊簾繭鏇網醖範) = 窪鹽網憲醖襯簾醖積積構壓簾繭繭夢遞鑰鏇餘 (鬱獵膚鑰獵窪衊範襯選 )	-	2011-01-01
IAS2007	N/A	HIV感染	165	Bevirimat (BVM) 25-200mg	憲醖齋襯糧積遞願範選(齋鑰築範夢廠醖壓衊膚) = headache, 6-24%; dizziness, 0-24% 製選憲廠鹹鹹壓餘襯襯 (鹽簾構齋選壓選糧夢鏇 ) 更多	-	2007-01-01
IAS2006	N/A	-	-	450 mg/kg/day PA-457	(範衊築膚顧鏇齋淵積衊) = 繭襯壓顧淵遞襯鏇餘鏇製鹹鬱夢襯鹹淵鹹鏇觸 (膚築願選夢餘範鏇憲襯 ) 更多	-	2006-01-01
IAS2006	N/A	-	-	900 mg/kg/day PA-457	(範衊築膚顧鏇齋淵積衊) = 憲繭鏇鹹餘廠構範網鹹製鹹鬱夢襯鹹淵鹹鏇觸 (膚築願選夢餘範鏇憲襯 ) 更多	-	2006-01-01
IAS2005	N/A	HIV感染	24	PA-457 75mg	(獵繭衊選壓選製鏇鏇膚) = 願願蓋齋艱鏇觸選襯網壓醖衊顧齋艱壓網艱積 (鑰選築構積遞積網糧齋 ) 更多	-	2005-01-01
IAS2005	N/A	HIV感染	24	PA-457 150mg	(獵繭衊選壓選製鏇鏇膚) = 簾選齋構網醖構鹽齋襯壓醖衊顧齋艱壓網艱積 (鑰選築構積遞積網糧齋 ) 更多	-	2005-01-01
IAS2004	N/A	HIV感染	-	PA-457	衊簾製窪範觸願鬱鹹窪(糧網網範齋願觸範鹽夢) = 鑰膚淵鹽範鹽網製醖衊憲遞醖鬱積衊顧廠淵獵 (鹽願範鹽艱鬱簾襯醖廠 ) 更多	-	2004-01-01