BEVIRIMAT

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C36H56O6
Molecular Weight	584.8262
Optical Activity	UNSPECIFIED
Defined Stereocenters	10 / 10
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(=C)[C@@H]1CC[C@@]2(CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](OC(=O)CC(C)(C)C(O)=O)C(C)(C)[C@@H]5CC[C@@]34C)[C@@H]12)C(O)=O

InChI

InChIKey=YJEJKUQEXFSVCJ-WRFMNRASSA-N

InChI=1S/C36H56O6/c1-21(2)22-12-17-36(30(40)41)19-18-34(8)23(28(22)36)10-11-25-33(7)15-14-26(42-27(37)20-31(3,4)29(38)39)32(5,6)24(33)13-16-35(25,34)9/h22-26,28H,1,10-20H2,2-9H3,(H,38,39)(H,40,41)/t22-,23+,24-,25+,26-,28+,33-,34+,35+,36-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C36H56O6
Molecular Weight	584.8262
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	10 / 10
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14573704 | https://www.ncbi.nlm.nih.gov/pubmed/19024627 | https://www.ncbi.nlm.nih.gov/pubmed/17638699 | http://adisinsight.springer.com/drugs/800013764

Bevirimat (3-O-(3',3'-dimethylsuccinyl) betulinic acid or MPC-4326 or PA-457) potently inhibits replication of both WT and drug-resistant HIV-1 isolates and demonstrate that the compound acts by disrupting a late step in Gag processing involving conversion of the capsid precursor (p25) to mature capsid protein (p24). Bevirimat inhibits replication of both wild-type and drug-resistant HIV-1 isolates in vitro, achieving similar 50% inhibitory concentration values with both categories. Serial drug passage studies have identified six single amino acid substitutions that independently confer bevirimat resistance. These resistance mutations occur at or near the CA-SP1 cleavage site, which is not a known target for resistance to other antiretroviral drugs. Bevirimat has been in phase 2 trial for the treatment of HIV infections. Bevirimat has demonstrated a consistent pharmacokinetic profile in healthy volunteers and HIV-infected patients. The demonstration of an antiviral effect following a single oral dose of bevirimat validates maturation inhibition as a potential target for antiretroviral therapeutics in humans.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Gag-Pol polyprotein 6 Target ID: CHEMBL5823 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27893830 \| https://www.ncbi.nlm.nih.gov/pubmed/23144615 \| https://www.ncbi.nlm.nih.gov/pubmed/22151792 \| https://www.ncbi.nlm.nih.gov/pubmed/14573704	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 156 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19024627	Primary		Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
31.6 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BEVIRIMAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
43.7 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BEVIRIMAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
58 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BEVIRIMAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	BEVIRIMAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
8 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	25 mg 1 times / day multiple, oral dose: 25 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BEVIRIMAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
11.9 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	BEVIRIMAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
25.1 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	BEVIRIMAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
599.5 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BEVIRIMAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
827.9 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BEVIRIMAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1113.7 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BEVIRIMAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
88.2 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	BEVIRIMAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
156.5 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	25 mg 1 times / day multiple, oral dose: 25 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BEVIRIMAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
180.9 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	BEVIRIMAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
382.9 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	BEVIRIMAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
56.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BEVIRIMAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
61.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BEVIRIMAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
62.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BEVIRIMAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.75 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	25 mg 1 times / day multiple, oral dose: 25 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BEVIRIMAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYPs 29 P-gp 1741	UGT2B7 456 UGT1A3 470 UGT1A8 323 UGT1A4 399 UGT2B17 237 UGT1A10 331 UGT1A6 343 CYPs 33 UGT2B15 236 UGT1A1 479 UGT1A9 423 UGT1A7 249 UGT2B4 278	CYP3A 142

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYPs 35	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19024627/	no
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19024627/	no
CYP3A 317	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/17596104/	no	likely (expression study) Comment: Urinary 6β-hydroxycortisol/cortisol ratio was not influenced by Bevirimat administration. Sources: https://pubmed.ncbi.nlm.nih.gov/17596104/

Drug as victim

Target	Modality	Activity
UGT1A3 470	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17151190/	major [Km 13 uM]
UGT2B7 456	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17151190/	minor [Km 6 uM]
UGT1A4 399	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17151190/	minor
CYPs 33	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17596104/	no
UGT1A1 479	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17151190/	no
UGT1A10 331	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17151190/	no
UGT1A6 343	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17151190/	no
UGT1A7 249	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17151190/	no
UGT1A8 323	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17151190/	no
UGT1A9 423	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17151190/	no
UGT2B15 236	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17151190/	no
UGT2B17 237	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17151190/	no
UGT2B4 278	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17151190/	no

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P001ZV0	https://www.1pchem.com/search?query=1P001ZV0
AK Scientific	3485AH	https://aksci.com/item_detail.php?cat=3485AH
AstaTech	44148	http://astatechinc.com/CPSResult.php?CRNO=44148
Biopurify Phytochemicals	BP3086	https://www.phytopurify.com/search.do?a=s&searchtype=3&psize=10&q=BP3086&searchhtmp=simplesearch&t=1
BLD Pharm	BD630448	http://www.bldpharm.com/search/Search.html?keyword=BD630448
BOC Sciences	174022-42-5	http://www.bocsci.com/description.asp?cas=174022-42-5
Cayman Chemical	21339	http://www.caymanchem.com/app/template/Product.vm/catalog/21339
Chem Scene	CS-3010	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3010
eMolecules	46301175	https://orderbb.emolecules.com/search/#?query=46301175
Lab Seeker	SC-96858	http://www.labseeker.com/search.php?keywords=SC-96858&category=0
LabSeeker	SC-96858	http://www.labseeker.com/search.php?keywords=SC-96858&category=0
mcule	MCULE-8373483440	https://mcule.com/MCULE-8373483440/
MedChem Express	HY-N0842	https://www.medchemexpress.com/search.html?q=HY-N0842&ft=&fa=&fp=
MolPort	MolPort-006-170-151	https://www.molport.com/shop/molecule-link/MolPort-006-170-151
MuseChem	I002271	https://www.musechem.com/product/I002271.html
Sigma Aldrich	SML2057	http://www.sigmaaldrich.com/catalog/search?term=SML2057&interface=All&N=0&mode=match%20partialmax&lang=en®ion=US&focus=product
TargetMol	T5782	https://www.targetmol.com/search?keyword=T5782
Tetrahedron	TS73398	http://www.thsci.com/search.do?q=TS73398

PubMed

Title	Date	PubMed
Synthesis and biological evaluation of a new derivative of bevirimat that targets the Gag CA-SP1 cleavage site.	2013-04	23399723
A single polymorphism in HIV-1 subtype C SP1 is sufficient to confer natural resistance to the maturation inhibitor bevirimat.	2011-07	21502630
Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat.	2010-04-20	20406463
Betulinic acid derivatives as human immunodeficiency virus type 2 (HIV-2) inhibitors.	2009-12-10	19526990
New small-molecule inhibitor class targeting human immunodeficiency virus type 1 virion maturation.	2009-12	19805571
Anti-AIDS agents. 78. Design, synthesis, metabolic stability assessment, and antiviral evaluation of novel betulinic acid derivatives as potent anti-human immunodeficiency virus (HIV) agents.	2009-05-28	19388685
Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice.	2007-11-28	18043758
Phase I and II study of the safety, virologic effect, and pharmacokinetics/pharmacodynamics of single-dose 3-o-(3',3'-dimethylsuccinyl)betulinic acid (bevirimat) against human immunodeficiency virus infection.	2007-10	17638699
The 3-O-(3',3'-dimethylsuccinyl) derivative of betulinic acid (DSB) inhibits the assembly of virus-like particles in HIV-1 Gag precursor-expressing cells.	2007	18240859
Human immunodeficiency virus type 1 resistance to the small molecule maturation inhibitor 3-O-(3',3'-dimethylsuccinyl)-betulinic acid is conferred by a variety of single amino acid substitutions at the CA-SP1 cleavage site in Gag.	2006-12	17035324
In vitro resistance to the human immunodeficiency virus type 1 maturation inhibitor PA-457 (Bevirimat).	2006-11	16956950
Anti-AIDS agents 69. Moronic acid and other triterpene derivatives as novel potent anti-HIV agents.	2006-09-07	16942019
Determinants of activity of the HIV-1 maturation inhibitor PA-457.	2006-06-08	16930665
3-O-(3',3'-dimethysuccinyl) betulinic acid inhibits maturation of the human immunodeficiency virus type 1 Gag precursor assembled in vitro.	2006-06	16731910
Synthesis and anti-HIV activity of bi-functional betulinic acid derivatives.	2006-04-01	16314103
3-O-Glutaryl-dihydrobetulin and related monoacyl derivatives as potent anti-HIV agents.	2004-12-06	15501054
Bifunctional anti-human immunodeficiency virus type 1 small molecules with two novel mechanisms of action.	2004-02	14742233
Small-molecule inhibition of human immunodeficiency virus type 1 replication by specific targeting of the final step of virion maturation.	2004-01	14694123
Anti-human immunodeficiency virus activity of YK-FH312 (a betulinic acid derivative), a novel compound blocking viral maturation.	2001-04	11257038
Anti-AIDS agents 38. Anti-HIV activity of 3-O-acyl ursolic acid derivatives.	2000-12	11141100
Synthesis and anti-HIV activity of 3-alkylamido-3-deoxy-betulinic acid derivatives.	2000-09	10993248
Anti-AIDS agents. 34. Synthesis and structure-activity relationships of betulin derivatives as anti-HIV agents.	1998-11-05	9804704
Anti-AIDS agents--XXVII. Synthesis and anti-HIV activity of betulinic acid and dihydrobetulinic acid derivatives.	1997-12	9459011
Betulinic acid and dihydrobetulinic acid derivatives as potent anti-HIV agents.	1996-03-01	8676334

Patents

Sample Use Guides

In Vivo Use Guide

Four cohorts of six HIV-infected adults, with CD4 counts of >200 and plasma viral loads of 5,000 to 250,000 transcripts/ml and not currently receiving antiretroviral therapy, were randomized to receive a single oral dose of placebo, 75, 150, or 250 mg of bevirimat. The study was a 10-day, randomised, double-blind, placebo-controlled, dose escalation study. A total of 48 healthy male volunteers, aged 19-54 years, took part in the study. Treatment was administered for 10 days in six escalating dose cohorts (n = 8 in each cohort; 6 bevirimat, 2 placebo). The doses of bevirimat given in each successive cohort were 25 mg, 50 mg, 75 mg (with 150 mg loading dose), 100 mg, 150 mg and 200mg. Safety follow-up was performed 28 days after the first dose.

Route of Administration: Oral

In Vitro Use Guide

Bevirimat (PA-457) was shown to be a potent in vitro inhibitor of HIV-1 replication. In assays using patient-derived WT virus isolates, PA-457 exhibited a mean IC50 of 10.3 nM.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:45:11 GMT 2025` Edited by `admin` on `Mon Mar 31 18:45:11 GMT 2025`
Record UNII	S125DW66N8
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

BEVIRIMAT

Official Name

English

MPC-4326

Preferred Name

English

BEVIRIMAT [MI]

Common Name

English

PA-103001

Code

English

YK-FH312

Common Name

English

bevirimat [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1660