TEMSAVIR

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H23N7O4
Molecular Weight	473.4839
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

COC1=CN=C(N2C=NC(C)=N2)C3=C1C(=CN3)C(=O)C(=O)N4CCN(CC4)C(=O)C5=CC=CC=C5

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

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Description

Fostemsavir (BMS-663068) is an investigational attachment inhibitor with a unique mechanism of action. It is a prodrug of temsavir, which binds to HIV envelope glycoprotein 120 (gp120), thereby preventing viral attachment to the host CD4 cell surface receptor. In the absence of effective binding of HIV gp120 with the host CD4 receptor, HIV does not enter the host cell. Because fostemsavir has a novel mechanism of action, the drug should have full activity against HIV strains that have developed resistance to other classes of antiretroviral medications. In a phase 2b study of treatment-experienced individuals, fostemsavir appeared to be well tolerated. Phase 3 studies are ongoing.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Human immunodeficiency virus 1 34	Inhibitor 8,504
Human immunodeficiency virus 1 34	Inhibitor 8,504		2.26 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 156	Primary		Phase III 665	Unknown
HIV-1 infection 156	Primary		Phase III 665	Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
3.18 ug/mL	1200 mg 2 times / day multiple, oral		TEMSAVIR plasma	Homo sapiens
3.61 ug/mL	1200 mg 2 times / day multiple, oral		TEMSAVIR plasma	Homo sapiens
3.39 ug/mL	1200 mg 2 times / day multiple, oral		TEMSAVIR plasma	Homo sapiens
2.55 ug/mL	1200 mg single, oral		TEMSAVIR plasma	Homo sapiens
3.39 μg/mL	1200 mg 2 times / day multiple, oral		TEMSAVIR plasma	Homo sapiens
1770 ng/mL	600 mg 2 times / day multiple, oral	other antiretroviral drugs	TEMSAVIR plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
19.5 ug*h/mL	1200 mg 2 times / day multiple, oral		TEMSAVIR plasma	Homo sapiens
22.5 ug*h/mL	1200 mg 2 times / day multiple, oral		TEMSAVIR plasma	Homo sapiens
42.6 ug*h/mL	1200 mg 2 times / day multiple, oral		TEMSAVIR plasma	Homo sapiens
13.8 ug*h/mL	1200 mg single, oral		TEMSAVIR plasma	Homo sapiens
42.6 μg × h/mL	1200 mg 2 times / day multiple, oral		TEMSAVIR plasma	Homo sapiens
12900 ng × h/mL	600 mg 2 times / day multiple, oral	other antiretroviral drugs	TEMSAVIR plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
11 h	600 mg single, oral		TEMSAVIR plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
26.9%	600 mg single, oral		TEMSAVIR plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
600 mg 2 times / day steady, oral Recommended	unhealthy, 17-43 years	Disc. AE: Immune reconstitution inflammatory syndrome... Other AEs: Nausea, Diarrhea...
600 mg 2 times / day steady, oral Recommended	healthy, 18-49 years	Other AEs: Scleral icterus, Abdominal pain...
600 mg 2 times / day steady, oral Recommended	healthy, 18-49 years	Other AEs: Headache...
600 mg 2 times / day steady, oral Recommended	healthy, 18-49 years	Other AEs: Scleral icterus, Abdominal pain...
1050 mg 2 times / day steady, oral Studied dose	unhealthy, adults	Other AEs: Headache...

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AEs

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AE	Significance	Dose	Population
Nausea	grade 1-4, 10%	600 mg 2 times / day steady, oral Recommended	unhealthy, 17-43 years
Immune reconstitution inflammatory syndrome	grade 1-4, 2%	600 mg 2 times / day steady, oral Recommended	unhealthy, 17-43 years
Somnolence	grade 1-4, 2%	600 mg 2 times / day steady, oral Recommended	unhealthy, 17-43 years
Vomiting	grade 1-4, 2%	600 mg 2 times / day steady, oral Recommended	unhealthy, 17-43 years
Abdominal pain	grade 1-4, 3%	600 mg 2 times / day steady, oral Recommended	unhealthy, 17-43 years

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2,252 inducer 1,087	substrate 1,193 inhibitor 2,438	substrate 1,388 inhibitor 2,507	inhibitor 2,217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B1 1,079 OATP1B3 961 CYP 110 UGT 45 BCRP 910 MATE2 267 CYP1A2 2,153 CYP2B6 926 CYP2C8 1,057 CYP2C19 2,057 CYP2A6 879 UGT1A1 246 UGT1A4 98 UGT1A9 148 UGT1A6 136 UGT2B7 197 P-gp 1,741 OAT1 725 OAT3 747 MATE1 415 MRP2 499 NTCP 39 OCT2 779 BSEP 550 OCT1 620	CYP3A 220 P-gp 2,052 BCRP 697 esterase 74 UGT 219 CYP1A1 389 CYP1A2 1,197 CYP2A6 626 CYP1B1 104 CYP2B6 776 CYP2C8 810 CYP2C19 1,119 FMO3 77 CYP4A11 137 CYP2E1 729 CYP3A5 446	CYP1A2 832 CYP2B6 669

Drug as perpetrator

Show entries

Target	Modality	Activity	Metabolite
OAT1 730	inhibitor 4,027	no [IC50 110 uM]	temsavir 5
OCT1 656	inhibitor 4,027	no [IC50 32.8 uM]	temsavir 5
UGT1A6 171	inhibitor 4,027	no [IC50 >10 uM]	temsavir 5
UGT1A9 155	inhibitor 4,027	no [IC50 >10 uM]	temsavir 5
UGT2B7 210	inhibitor 4,027	no [IC50 >10 uM]

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Drug as victim

Show entries

Target	Modality	Activity	Metabolite
UGT 219	substrate 4,014	minor	temsavir 5
CYP1A1 389	substrate 4,014	no	temsavir 5
CYP1A2 1,197	substrate 4,014	no	temsavir 5
CYP1B1 104	substrate 4,014	no	temsavir 5
CYP2A6 626	substrate 4,014	no	temsavir 5

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2,263	inhibitor 2,237		temsavir 5

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
001 Chemical	DY575616	https://www.001chemical.com/chem/864953-29-7
AA Blocks	AA00GTZ5	https://www.aablocks.com/goods/Goods/detail?id=AA00GTZ5
Acadechem	ACDS-0781672	http://acadechemical.com/product/229218
Achemtek	0102-013953	http://www.achemtek.com/864953-29-7
Adooq BioScience	A15025	https://www.adooq.com/bms-663068.html

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PubMed

Title	Date	PubMed
No data available in table

Patents

Sample Use Guides

In Vivo Use Guide

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

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.

Show entries

Name

Type

Language

temsavir [INN]

Preferred Name

English

TEMSAVIR

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 [USAN]

Common Name

English

BMS-626529

Code

English

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Classification Tree

Code System

Code

Antiviral Agent

NCI_THESAURUS

C1660

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Code System

Code

Type

Description

ChEMBL

CHEMBL3301620

PRIMARY

CAS

701213-36-7

PRIMARY

DAILYMED

4B6J53W8N3

PRIMARY

MERCK INDEX

m12225

PRIMARY

FDA UNII

4B6J53W8N3

PRIMARY

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ACTIVE MOIETY


					4B6J53W8N3

TEMSAVIR

PRODRUG (METABOLITE ACTIVE)


					97IQ273H4L

FOSTEMSAVIR

SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator