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Details

Stereochemistry ACHIRAL
Molecular Formula C24H23N7O4
Molecular Weight 473.4848
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TEMSAVIR

SMILES

Cc1ncn(-c2c3c(c(c[nH]3)C(=O)C(=O)N4CCN(CC4)C(=O)c5ccccc5)c(cn2)OC)n1

InChI

InChIKey=QRPZBKAMSFHVRW-UHFFFAOYSA-N
InChI=1S/C24H23N7O4/c1-15-27-14-31(28-15)22-20-19(18(35-2)13-26-22)17(12-25-20)21(32)24(34)30-10-8-29(9-11-30)23(33)16-6-4-3-5-7-16/h3-7,12-14,25H,8-11H2,1-2H3

HIDE SMILES / InChI

Molecular Formula C24H23N7O4
Molecular Weight 473.4848
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: https://www.ncbi.nlm.nih.gov/pubmed/23774428

Temsavir (BMS-626529) is an attachment inhibitor (AI) in clinical development (administered as prodrug BMS-663068) that binds to HIV-1 gp120. Temsavir displays in vitro activity against HIV-1 envelopes with C-C chemokine receptor type 5 (CCR5-), C-X-C chemokine receptor type 4 (CXCR4), and dual tropism. It also is active against almost all HIV-1 subtypes tested except for subtype CRF01-AE and possibly group O. Temsavir can inhibit both CD4-induced and CD4-independent formation of the "open state" four-stranded gp120 bridging sheet, and the subsequent formation and exposure of the chemokine co-receptor binding site. This unique mechanism of action prevents the initial interaction of HIV-1 with the host CD4+ T cell, and subsequent HIV-1 binding and entry. Temsavir is administered as a phosphonooxymethyl ester prodrug (BMS-663068), which was developed to improve the solubility and dissolution of Temsavir. Temsavir is currently being investigated clinically through the use of the prodrug BMS-663068, and a Phase III study of BMS-663068 in HIV-1-infected treatment-experienced subjects is ongoing (NCT02362503).

Originator

Curator's Comment:: # Bristol-Myers Squibb

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
2.25999999999999979 nM [IC50]
Conditions

Conditions

PubMed

PubMed

TitleDatePubMed
In vitro antiviral characteristics of HIV-1 attachment inhibitor BMS-626529, the active component of the prodrug BMS-663068.
2012 Jul
Patents

Sample Use Guides

Phase 1: BMS-663068 (a prodrug of temsavir) 600 mg tablets orally twice daily for 8 days
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment:: Temsavir (BMS-626529) had half-maximal effective concentration (EC(50)) values of <10 nM against the vast majority of HIV-1 viral isolates; however, susceptibility varied by >6 log(10), with half-maximal effective concentration values in the low pM range against the most susceptible viruses.
Temsavir (BMS-626529) inhibits HIV-1 gp120 with IC50 values of 2.26 nM, 0.34 nM and 1.3 nM for HIV-1 subtype A, B, and C envelope, respectively.
Substance Class Chemical
Created
by admin
on Sat Jun 26 04:44:20 UTC 2021
Edited
by admin
on Sat Jun 26 04:44:20 UTC 2021
Record UNII
4B6J53W8N3
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TEMSAVIR
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
1,2-ETHANEDIONE, 1-(4-BENZOYL-1-PIPERAZINYL)-2-(4-METHOXY-7-(3-METHYL-1H-1,2,4-TRIAZOL-1-YL)-1H-PYRROLO(2,3-C)PYRIDIN-3-YL)-
Systematic Name English
TEMSAVIR [INN]
Common Name English
TEMSAVIR [USAN]
Common Name English
BMS-626529
Code English
PIPERAZINE, 1-BENZOYL-4-((4-METHOXY-7-(3-METHYL-1H-1,2,4-TRIAZOL-1-YL)-1H-PYRROLO(2,3-C)PYRIDIN-3-YL)OXOACETYL)-
Systematic Name English
TEMSAVIR [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1660
Created by admin on Sat Jun 26 04:44:20 UTC 2021 , Edited by admin on Sat Jun 26 04:44:20 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL3301620
Created by admin on Sat Jun 26 04:44:20 UTC 2021 , Edited by admin on Sat Jun 26 04:44:20 UTC 2021
PRIMARY
CAS
701213-36-7
Created by admin on Sat Jun 26 04:44:20 UTC 2021 , Edited by admin on Sat Jun 26 04:44:20 UTC 2021
PRIMARY
FDA UNII
4B6J53W8N3
Created by admin on Sat Jun 26 04:44:20 UTC 2021 , Edited by admin on Sat Jun 26 04:44:20 UTC 2021
PRIMARY
EPA CompTox
701213-36-7
Created by admin on Sat Jun 26 04:44:20 UTC 2021 , Edited by admin on Sat Jun 26 04:44:20 UTC 2021
PRIMARY
PUBCHEM
11317439
Created by admin on Sat Jun 26 04:44:20 UTC 2021 , Edited by admin on Sat Jun 26 04:44:20 UTC 2021
PRIMARY
NCI_THESAURUS
C152553
Created by admin on Sat Jun 26 04:44:20 UTC 2021 , Edited by admin on Sat Jun 26 04:44:20 UTC 2021
PRIMARY
INN
9941
Created by admin on Sat Jun 26 04:44:20 UTC 2021 , Edited by admin on Sat Jun 26 04:44:20 UTC 2021
PRIMARY
DRUG BANK
DB14675
Created by admin on Sat Jun 26 04:44:20 UTC 2021 , Edited by admin on Sat Jun 26 04:44:20 UTC 2021
PRIMARY
Related Record Type Details
TRANSPORTER -> SUBSTRATE
Drugs that induce or inhibit CYP3A, P-gp, and BCRP may affect temsavir plasma concentrations.
METABOLIC ENZYME -> SUBSTRATE
Drugs that induce or inhibit CYP3A, P-gp, and BCRP may affect temsavir plasma concentrations.
EXCRETED UNCHANGED
FECAL
EXCRETED UNCHANGED
URINE
TRANSPORTER -> INHIBITOR
TRANSPORTER -> SUBSTRATE
Drugs that induce or inhibit CYP3A, P-gp, and BCRP may affect temsavir plasma concentrations.
TRANSPORTER -> INHIBITOR
BINDER->LIGAND
BINDING
Related Record Type Details
PRODRUG -> METABOLITE ACTIVE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Blood-to-plasma ratio PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC ORAL ADMINISTRATION

Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL ADMINISTRATION