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
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
| 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 |
DescriptionCurator's Comment:: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/22547625
https://www.ncbi.nlm.nih.gov/pubmed/23774428
Curator's Comment:: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/22547625
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).
Approval Year
Sample Use Guides
Phase 1: BMS-663068 (a prodrug of temsavir) 600 mg tablets orally twice daily for 8 days
Phase 2: BMS-663068 (a prodrug of temsavir) 600 mg tablets orally twice daily for 48 weeks or longer
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
Edited
Sat Jun 26 04:44:20 UTC 2021
by
admin
on
Sat Jun 26 04:44:20 UTC 2021
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| Record UNII |
4B6J53W8N3
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Validated (UNII)
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C1660
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11317439
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C152553
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9941
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DB14675
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| Related Record | Type | Details | ||
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TRANSPORTER -> SUBSTRATE |
Drugs that induce or inhibit CYP3A, P-gp, and BCRP may affect temsavir plasma concentrations.
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METABOLIC ENZYME -> SUBSTRATE |
Drugs that induce or inhibit CYP3A, P-gp, and BCRP may affect temsavir plasma concentrations.
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EXCRETED UNCHANGED |
FECAL
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EXCRETED UNCHANGED |
URINE
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> SUBSTRATE |
Drugs that induce or inhibit CYP3A, P-gp, and BCRP may affect temsavir plasma concentrations.
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TRANSPORTER -> INHIBITOR | |||
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BINDER->LIGAND |
BINDING
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PRODRUG -> METABOLITE ACTIVE |
| Related Record | Type | Details | ||
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ACTIVE MOIETY |
| Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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| Blood-to-plasma ratio | PHARMACOKINETIC |
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| Biological Half-life | PHARMACOKINETIC |
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ORAL ADMINISTRATION |
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| Volume of Distribution | PHARMACOKINETIC |
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| Tmax | PHARMACOKINETIC |
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ORAL ADMINISTRATION |
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