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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
Structure of TEMSAVIR

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

HIDE SMILES / InChI

Molecular Formula C24H23N7O4
Molecular Weight 473.4839
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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).

Originator

Curator's Comment: # Bristol-Myers Squibb

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
2.26 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1770 ng/mL
600 mg 2 times / day multiple, oral
dose: 600 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered: other antiretroviral drugs
TEMSAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
3.39 μg/mL
1200 mg 2 times / day multiple, oral
dose: 1200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TEMSAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FED
2.55 ug/mL
1200 mg single, oral
dose: 1200 mg
route of administration: oral
experiment type: single
co-administered:
TEMSAVIR plasma
Homo sapiens
3.18 ug/mL
1200 mg 1 times / 12 hours multiple, oral
dose: 1200 mg
route of administration: oral
experiment type: multiple
co-administered:
TEMSAVIR plasma
Homo sapiens
3.38999999999999 ug/mL
1200 mg 1 times / 12 hours multiple, oral
dose: 1200 mg
route of administration: oral
experiment type: multiple
co-administered:
TEMSAVIR plasma
Homo sapiens
3.61 ug/mL
1200 mg 1 times / 12 hours multiple, oral
dose: 1200 mg
route of administration: oral
experiment type: multiple
co-administered:
TEMSAVIR plasma
Homo sapiens
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
12900 ng × h/mL
600 mg 2 times / day multiple, oral
dose: 600 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered: other antiretroviral drugs
TEMSAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
42.6 μg × h/mL
1200 mg 2 times / day multiple, oral
dose: 1200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TEMSAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FED
13.8 ug*h/mL
1200 mg single, oral
dose: 1200 mg
route of administration: oral
experiment type: single
co-administered:
TEMSAVIR plasma
Homo sapiens
19.5 ug*h/mL
1200 mg 1 times / 12 hours multiple, oral
dose: 1200 mg
route of administration: oral
experiment type: multiple
co-administered:
TEMSAVIR plasma
Homo sapiens
22.5 ug*h/mL
1200 mg 1 times / 12 hours multiple, oral
dose: 1200 mg
route of administration: oral
experiment type: multiple
co-administered:
TEMSAVIR plasma
Homo sapiens
42.6 ug*h/mL
1200 mg 1 times / 12 hours multiple, oral
dose: 1200 mg
route of administration: oral
experiment type: multiple
co-administered:
TEMSAVIR plasma
Homo sapiens
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
11 h
600 mg single, oral
dose: 600 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TEMSAVIR plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
26.9%
600 mg single, oral
dose: 600 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TEMSAVIR plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Disc. AE: Immune reconstitution inflammatory syndrome...
Other AEs: Nausea, Diarrhea...
AEs leading to
discontinuation/dose reduction:
Immune reconstitution inflammatory syndrome (grade 3, 3%)
Other AEs:
Nausea (grade 1-4, 10%)
Diarrhea (grade 1-4, 4%)
Headache (grade 1-4, 4%)
Abdominal pain (grade 1-4, 3%)
Dyspepsia (grade 1-4, 3%)
Fatigue (grade 1-4, 3%)
Rash (grade 1-4, 3%)
Sleep disturbance (grade 1-4, 3%)
Immune reconstitution inflammatory syndrome (grade 1-4, 2%)
Somnolence (grade 1-4, 2%)
Vomiting (grade 1-4, 2%)
ALT increased (grade 3-4, 5%)
AST increased (grade 3-4, 4%)
Direct bilirubin increased (grade 3, 7%)
Bilirubin increased (grade 3-4, 3%)
Creatinine increased (grade 3-4, 19%)
Creatine kinase increased (grade 3-4, 2%)
Hemoglobin decreased (grade 3-4, 6%)
Hyperglycemia (grade 3-4, 4%)
Lipase increased (grade 3-4, 5%)
Neutrophils reduced (grade 3-4, 4%)
Blood triglycerides increased (grade 3-4, 5%)
Sources:
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
ritonavir(100 mg; oral; 1/day)
Sources:
healthy, 18-49 years
n = 18
Health Status: healthy
Age Group: 18-49 years
Sex: M+F
Population Size: 18
Sources:
Other AEs: Scleral icterus, Abdominal pain...
Other AEs:
Scleral icterus (5.6%)
Abdominal pain (5.6%)
Nausea (5.6%)
Sources:
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
atazanavir(300 mg; oral; 1/day)
ritonavir(100 mg; oral; 1/day)
Sources:
healthy, 18-49 years
n = 36
Health Status: healthy
Age Group: 18-49 years
Sex: M+F
Population Size: 36
Sources:
Other AEs: Scleral icterus, Abdominal pain...
Other AEs:
Scleral icterus (27.8%)
Abdominal pain (11.1%)
Headache (13.9%)
Dizziness (5.6%)
Nausea (8.3%)
Musculoskeletal chest pain (2.8%)
Sources:
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
healthy, 18-49 years
n = 36
Health Status: healthy
Age Group: 18-49 years
Sex: M+F
Population Size: 36
Sources:
Other AEs: Headache...
Other AEs:
Headache (5.6%)
Sources:
1050 mg 2 times / day steady, oral (mean)
Studied dose
Dose: 1050 mg, 2 times / day
Route: oral
Route: steady
Dose: 1050 mg, 2 times / day
Co-administed with::
raltegravir and tenofovir disoproxil fumarate
Sources:
unhealthy, adults
n = 200
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: adults
Sex: M+F
Population Size: 200
Sources:
Other AEs: Headache...
Other AEs:
Headache (grade 1, 14%)
Sources:
1200 mg 1 times / day steady, oral
Studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: steady
Dose: 1200 mg, 1 times / day
Co-administed with::
raltegravir and tenofovir disoproxil fumarate
Sources:
unhealthy, adults
n = 50
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: adults
Sex: M+F
Population Size: 50
Sources:
Disc. AE: Disseminated tuberculosis, Back pain...
AEs leading to
discontinuation/dose reduction:
Disseminated tuberculosis (2%)
Back pain (2%)
Sources:
400 mg 2 times / day steady, oral
Studied dose
Dose: 400 mg, 2 times / day
Route: oral
Route: steady
Dose: 400 mg, 2 times / day
Co-administed with::
raltegravir and tenofovir disoproxil fumarate
Sources:
unhealthy, adults
n = 50
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: adults
Sex: M+F
Population Size: 50
Sources:
Disc. AE: Ischaemia...
AEs leading to
discontinuation/dose reduction:
Ischaemia (2%)
Sources:
800 mg 2 times / day steady, oral
Studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: steady
Dose: 800 mg, 2 times / day
Co-administed with::
raltegravir and tenofovir disoproxil fumarate
Sources:
unhealthy, adults
n = 49
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: adults
Sex: M+F
Population Size: 49
Sources:
Disc. AE: Bone tuberculosis, Acute renal failure...
AEs leading to
discontinuation/dose reduction:
Bone tuberculosis (2%)
Acute renal failure (2%)
Sources:
2400 mg 2 times / day steady, oral
Highest studied dose
Dose: 2400 mg, 2 times / day
Route: oral
Route: steady
Dose: 2400 mg, 2 times / day
Sources:
healthy
n = 15
Health Status: healthy
Population Size: 15
Sources:
Other AEs: QT interval prolonged...
Other AEs:
QT interval prolonged
Sources:
AEs

AEs

AESignificanceDosePopulation
Nausea grade 1-4, 10%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Immune reconstitution inflammatory syndrome grade 1-4, 2%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Somnolence grade 1-4, 2%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Vomiting grade 1-4, 2%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Abdominal pain grade 1-4, 3%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Dyspepsia grade 1-4, 3%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Fatigue grade 1-4, 3%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Rash grade 1-4, 3%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Sleep disturbance grade 1-4, 3%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Diarrhea grade 1-4, 4%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Headache grade 1-4, 4%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Immune reconstitution inflammatory syndrome grade 3, 3%
Disc. AE
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Direct bilirubin increased grade 3, 7%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Creatinine increased grade 3-4, 19%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Creatine kinase increased grade 3-4, 2%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Bilirubin increased grade 3-4, 3%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
AST increased grade 3-4, 4%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Hyperglycemia grade 3-4, 4%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Neutrophils reduced grade 3-4, 4%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
ALT increased grade 3-4, 5%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Blood triglycerides increased grade 3-4, 5%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Lipase increased grade 3-4, 5%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Hemoglobin decreased grade 3-4, 6%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
optimized background therapy
Sources:
unhealthy, 17-43 years
n = 271
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 17-43 years
Sex: M+F
Population Size: 271
Sources:
Abdominal pain 5.6%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
ritonavir(100 mg; oral; 1/day)
Sources:
healthy, 18-49 years
n = 18
Health Status: healthy
Age Group: 18-49 years
Sex: M+F
Population Size: 18
Sources:
Nausea 5.6%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
ritonavir(100 mg; oral; 1/day)
Sources:
healthy, 18-49 years
n = 18
Health Status: healthy
Age Group: 18-49 years
Sex: M+F
Population Size: 18
Sources:
Scleral icterus 5.6%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
ritonavir(100 mg; oral; 1/day)
Sources:
healthy, 18-49 years
n = 18
Health Status: healthy
Age Group: 18-49 years
Sex: M+F
Population Size: 18
Sources:
Abdominal pain 11.1%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
atazanavir(300 mg; oral; 1/day)
ritonavir(100 mg; oral; 1/day)
Sources:
healthy, 18-49 years
n = 36
Health Status: healthy
Age Group: 18-49 years
Sex: M+F
Population Size: 36
Sources:
Headache 13.9%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
atazanavir(300 mg; oral; 1/day)
ritonavir(100 mg; oral; 1/day)
Sources:
healthy, 18-49 years
n = 36
Health Status: healthy
Age Group: 18-49 years
Sex: M+F
Population Size: 36
Sources:
Musculoskeletal chest pain 2.8%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
atazanavir(300 mg; oral; 1/day)
ritonavir(100 mg; oral; 1/day)
Sources:
healthy, 18-49 years
n = 36
Health Status: healthy
Age Group: 18-49 years
Sex: M+F
Population Size: 36
Sources:
Scleral icterus 27.8%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
atazanavir(300 mg; oral; 1/day)
ritonavir(100 mg; oral; 1/day)
Sources:
healthy, 18-49 years
n = 36
Health Status: healthy
Age Group: 18-49 years
Sex: M+F
Population Size: 36
Sources:
Dizziness 5.6%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
atazanavir(300 mg; oral; 1/day)
ritonavir(100 mg; oral; 1/day)
Sources:
healthy, 18-49 years
n = 36
Health Status: healthy
Age Group: 18-49 years
Sex: M+F
Population Size: 36
Sources:
Nausea 8.3%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Co-administed with::
atazanavir(300 mg; oral; 1/day)
ritonavir(100 mg; oral; 1/day)
Sources:
healthy, 18-49 years
n = 36
Health Status: healthy
Age Group: 18-49 years
Sex: M+F
Population Size: 36
Sources:
Headache 5.6%
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
healthy, 18-49 years
n = 36
Health Status: healthy
Age Group: 18-49 years
Sex: M+F
Population Size: 36
Sources:
Headache grade 1, 14%
1050 mg 2 times / day steady, oral (mean)
Studied dose
Dose: 1050 mg, 2 times / day
Route: oral
Route: steady
Dose: 1050 mg, 2 times / day
Co-administed with::
raltegravir and tenofovir disoproxil fumarate
Sources:
unhealthy, adults
n = 200
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: adults
Sex: M+F
Population Size: 200
Sources:
Back pain 2%
Disc. AE
1200 mg 1 times / day steady, oral
Studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: steady
Dose: 1200 mg, 1 times / day
Co-administed with::
raltegravir and tenofovir disoproxil fumarate
Sources:
unhealthy, adults
n = 50
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: adults
Sex: M+F
Population Size: 50
Sources:
Disseminated tuberculosis 2%
Disc. AE
1200 mg 1 times / day steady, oral
Studied dose
Dose: 1200 mg, 1 times / day
Route: oral
Route: steady
Dose: 1200 mg, 1 times / day
Co-administed with::
raltegravir and tenofovir disoproxil fumarate
Sources:
unhealthy, adults
n = 50
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: adults
Sex: M+F
Population Size: 50
Sources:
Ischaemia 2%
Disc. AE
400 mg 2 times / day steady, oral
Studied dose
Dose: 400 mg, 2 times / day
Route: oral
Route: steady
Dose: 400 mg, 2 times / day
Co-administed with::
raltegravir and tenofovir disoproxil fumarate
Sources:
unhealthy, adults
n = 50
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: adults
Sex: M+F
Population Size: 50
Sources:
Acute renal failure 2%
Disc. AE
800 mg 2 times / day steady, oral
Studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: steady
Dose: 800 mg, 2 times / day
Co-administed with::
raltegravir and tenofovir disoproxil fumarate
Sources:
unhealthy, adults
n = 49
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: adults
Sex: M+F
Population Size: 49
Sources:
Bone tuberculosis 2%
Disc. AE
800 mg 2 times / day steady, oral
Studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: steady
Dose: 800 mg, 2 times / day
Co-administed with::
raltegravir and tenofovir disoproxil fumarate
Sources:
unhealthy, adults
n = 49
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: adults
Sex: M+F
Population Size: 49
Sources:
QT interval prolonged
2400 mg 2 times / day steady, oral
Highest studied dose
Dose: 2400 mg, 2 times / day
Route: oral
Route: steady
Dose: 2400 mg, 2 times / day
Sources:
healthy
n = 15
Health Status: healthy
Population Size: 15
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [IC50 110 uM]
no [IC50 32.8 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >250 uM]
no [IC50 >250 uM]
no [IC50 >40 uM]
no [IC50 >40 uM]
no [IC50 >40 uM]
no [IC50 >40 uM]
no [IC50 >40 uM]
no [IC50 >40 uM]
no [IC50 >40 uM]
no [IC50 >40 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no [Inhibition 25 uM]
no
no
no
no
no
yes [IC50 12.2 uM]
yes [IC50 18.5 uM]
yes
yes
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
minor
no
no
no
no
no
no
no
no
no
no
no
no
no
yes
yes
yes
yes
yes (co-administration study)
Comment: coadministration of fostemsavir with rifampin significantly decreases temsavir plasma concentrations, reduced temsavir AUC by 80%; coadministration of fostemsavir with drugs that are strong CYP3A inducers result in decreased concentrations of temsavir.
Page: 35, 111, 112, 113
Tox targets

Tox targets

Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Model-Based Phase 3 Dose Selection for HIV-1 Attachment Inhibitor Prodrug BMS-663068 in HIV-1-Infected Patients: Population Pharmacokinetics/Pharmacodynamics of the Active Moiety, BMS-626529.
2016 May
Patents

Sample Use Guides

A phase 2b trial enrolled treatment-experienced adults with HIV infection and randomized study subjects to one of four doses of fostemsavir (400 mg twice daily, 800 mg twice daily, 600 mg once daily, or 1200 mg once daily).
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.
BMS-626529 (an active moiety of BMS-663068) exhibits an average EC50 against LAI of 0.7 +/-0.4 nM.
Substance Class Chemical
Created
by admin
on Sat Dec 16 17:22:00 GMT 2023
Edited
by admin
on Sat Dec 16 17:22:00 GMT 2023
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
Temsavir [WHO-DD]
Common Name English
TEMSAVIR [MI]
Common Name 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
Classification Tree Code System Code
NCI_THESAURUS C1660
Created by admin on Sat Dec 16 17:22:02 GMT 2023 , Edited by admin on Sat Dec 16 17:22:02 GMT 2023
Code System Code Type Description
ChEMBL
CHEMBL3301620
Created by admin on Sat Dec 16 17:22:02 GMT 2023 , Edited by admin on Sat Dec 16 17:22:02 GMT 2023
PRIMARY
CAS
701213-36-7
Created by admin on Sat Dec 16 17:22:02 GMT 2023 , Edited by admin on Sat Dec 16 17:22:02 GMT 2023
PRIMARY
MERCK INDEX
m12225
Created by admin on Sat Dec 16 17:22:02 GMT 2023 , Edited by admin on Sat Dec 16 17:22:02 GMT 2023
PRIMARY
FDA UNII
4B6J53W8N3
Created by admin on Sat Dec 16 17:22:02 GMT 2023 , Edited by admin on Sat Dec 16 17:22:02 GMT 2023
PRIMARY
EPA CompTox
DTXSID20462146
Created by admin on Sat Dec 16 17:22:02 GMT 2023 , Edited by admin on Sat Dec 16 17:22:02 GMT 2023
PRIMARY
USAN
ZZ-57
Created by admin on Sat Dec 16 17:22:02 GMT 2023 , Edited by admin on Sat Dec 16 17:22:02 GMT 2023
PRIMARY
PUBCHEM
11317439
Created by admin on Sat Dec 16 17:22:02 GMT 2023 , Edited by admin on Sat Dec 16 17:22:02 GMT 2023
PRIMARY
NCI_THESAURUS
C152553
Created by admin on Sat Dec 16 17:22:02 GMT 2023 , Edited by admin on Sat Dec 16 17:22:02 GMT 2023
PRIMARY
INN
9941
Created by admin on Sat Dec 16 17:22:02 GMT 2023 , Edited by admin on Sat Dec 16 17:22:02 GMT 2023
PRIMARY
DRUG BANK
DB14675
Created by admin on Sat Dec 16 17:22:02 GMT 2023 , Edited by admin on Sat Dec 16 17:22:02 GMT 2023
PRIMARY
SMS_ID
300000034446
Created by admin on Sat Dec 16 17:22:02 GMT 2023 , Edited by admin on Sat Dec 16 17:22:02 GMT 2023
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
TARGET ORGANISM->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