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Details

Stereochemistry ABSOLUTE
Molecular Formula C36H56O6
Molecular Weight 584.8276
Optical Activity UNSPECIFIED
Defined Stereocenters 10 / 10
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BEVIRIMAT

SMILES

C=C(C)[C@]1([H])CC[C@@]2(CC[C@]3(C)[C@]([H])(CC[C@]4([H])[C@@]5(C)CC[C@@]([H])(C(C)(C)[C@]5([H])CC[C@]43C)OC(=O)CC(C)(C)C(=O)O)[C@@]12[H])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 584.8276
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 9 / 10
E/Z Centers 0
Optical Activity UNSPECIFIED

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

Curator's Comment:: reference retrieved from https://www.ncbi.nlm.nih.gov/pubmed/14573704

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
11.9 μg/mL
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
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
6 μg/mL
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
58 μg/mL
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
8 μg/mL
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
31.6 μg/mL
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
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
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
180.9 μg × h/mL
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
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
88.2 μg × h/mL
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
1113.7 μg × h/mL
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
156.5 μg × h/mL
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
599.5 μg × h/mL
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
62.1 h
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
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
56.3 h
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
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
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
likely (expression study)
Comment: Urinary 6β-hydroxycortisol/cortisol ratio was not influenced by Bevirimat administration.
Drug as victim
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Synthesis and anti-HIV activity of 3-alkylamido-3-deoxy-betulinic acid derivatives.
2000 Sep
Small-molecule inhibition of human immunodeficiency virus type 1 replication by specific targeting of the final step of virion maturation.
2004 Jan
3-O-(3',3'-dimethysuccinyl) betulinic acid inhibits maturation of the human immunodeficiency virus type 1 Gag precursor assembled in vitro.
2006 Jun
In vitro resistance to the human immunodeficiency virus type 1 maturation inhibitor PA-457 (Bevirimat).
2006 Nov
New small-molecule inhibitor class targeting human immunodeficiency virus type 1 virion maturation.
2009 Dec
Betulinic acid derivatives as human immunodeficiency virus type 2 (HIV-2) inhibitors.
2009 Dec 10
Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat.
2010 Apr 20
A single polymorphism in HIV-1 subtype C SP1 is sufficient to confer natural resistance to the maturation inhibitor bevirimat.
2011 Jul
Synthesis and biological evaluation of a new derivative of bevirimat that targets the Gag CA-SP1 cleavage site.
2013 Apr
Patents

Sample Use Guides

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
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 Fri Jun 25 23:28:57 UTC 2021
Edited
by admin
on Fri Jun 25 23:28:57 UTC 2021
Record UNII
S125DW66N8
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BEVIRIMAT
INN   MI  
INN  
Official Name English
BEVIRIMAT [MI]
Common Name English
PA-103001
Code English
YK-FH312
Common Name English
BEVIRIMAT [INN]
Common Name English
MPC-4326
Code English
Classification Tree Code System Code
NCI_THESAURUS C1660
Created by admin on Fri Jun 25 23:28:57 UTC 2021 , Edited by admin on Fri Jun 25 23:28:57 UTC 2021
Code System Code Type Description
CAS
174022-42-5
Created by admin on Fri Jun 25 23:28:57 UTC 2021 , Edited by admin on Fri Jun 25 23:28:57 UTC 2021
PRIMARY
MESH
C479935
Created by admin on Fri Jun 25 23:28:57 UTC 2021 , Edited by admin on Fri Jun 25 23:28:57 UTC 2021
PRIMARY
MERCK INDEX
M2466
Created by admin on Fri Jun 25 23:28:57 UTC 2021 , Edited by admin on Fri Jun 25 23:28:57 UTC 2021
PRIMARY Merck Index
NCI_THESAURUS
C78044
Created by admin on Fri Jun 25 23:28:57 UTC 2021 , Edited by admin on Fri Jun 25 23:28:57 UTC 2021
PRIMARY
PUBCHEM
457928
Created by admin on Fri Jun 25 23:28:57 UTC 2021 , Edited by admin on Fri Jun 25 23:28:57 UTC 2021
PRIMARY
WIKIPEDIA
BEVIRIMAT
Created by admin on Fri Jun 25 23:28:57 UTC 2021 , Edited by admin on Fri Jun 25 23:28:57 UTC 2021
PRIMARY
FDA UNII
S125DW66N8
Created by admin on Fri Jun 25 23:28:57 UTC 2021 , Edited by admin on Fri Jun 25 23:28:57 UTC 2021
PRIMARY
ChEMBL
CHEMBL404519
Created by admin on Fri Jun 25 23:28:57 UTC 2021 , Edited by admin on Fri Jun 25 23:28:57 UTC 2021
PRIMARY
DRUG BANK
DB06581
Created by admin on Fri Jun 25 23:28:57 UTC 2021 , Edited by admin on Fri Jun 25 23:28:57 UTC 2021
PRIMARY
EPA CompTox
174022-42-5
Created by admin on Fri Jun 25 23:28:57 UTC 2021 , Edited by admin on Fri Jun 25 23:28:57 UTC 2021
PRIMARY
INN
8756
Created by admin on Fri Jun 25 23:28:57 UTC 2021 , Edited by admin on Fri Jun 25 23:28:57 UTC 2021
PRIMARY
Related Record Type Details
TARGET ORGANISM->INHIBITOR
Related Record Type Details
ACTIVE MOIETY