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Details

Stereochemistry ABSOLUTE
Molecular Formula C40H50N8O6
Molecular Weight 738.875
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DACLATASVIR

SMILES

COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C2=NC=C(N2)C3=CC=C(C=C3)C4=CC=C(C=C4)C5=CN=C(N5)[C@@H]6CCCN6C(=O)[C@@H](NC(=O)OC)C(C)C

InChI

InChIKey=FKRSSPOQAMALKA-CUPIEXAXSA-N
InChI=1S/C40H50N8O6/c1-23(2)33(45-39(51)53-5)37(49)47-19-7-9-31(47)35-41-21-29(43-35)27-15-11-25(12-16-27)26-13-17-28(18-14-26)30-22-42-36(44-30)32-10-8-20-48(32)38(50)34(24(3)4)46-40(52)54-6/h11-18,21-24,31-34H,7-10,19-20H2,1-6H3,(H,41,43)(H,42,44)(H,45,51)(H,46,52)/t31-,32-,33-,34-/m0/s1

HIDE SMILES / InChI

Molecular Formula C40H50N8O6
Molecular Weight 738.875
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Daclatasvir (BMS-790052) is a direct-acting antiviral agent against Hepatitis C Virus (HCV) used for the treatment of chronic HCV genotype 3 infection. Daclatasvir prevents RNA replication and virion assembly by binding to NS5A, a nonstructural phosphoprotein encoded by HCV. Binding to the N-terminus of the D1 domain of NS5A prevents its interaction with host cell proteins and membranes required for virion replication complex assembly.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
DAKLINZA

Cmax

ValueDoseCo-administeredAnalytePopulation
1295 ng/mL
60 mg single, oral
DACLATASVIR plasma
Homo sapiens
1582 ng/mL
60 mg 1 times / day steady-state, oral
DACLATASVIR plasma
Homo sapiens
291 ng/mL
10 mg single, oral
DACLATASVIR plasma
Homo sapiens
257 ng/mL
10 mg 1 times / day steady-state, oral
DACLATASVIR plasma
Homo sapiens
610 ng/mL
30 mg single, oral
DACLATASVIR plasma
Homo sapiens
734 ng/mL
30 mg 1 times / day steady-state, oral
DACLATASVIR plasma
Homo sapiens
148 ng/mL
60 mg 1 times / day steady-state, oral
DACLATASVIR plasma
Homo sapiens
1226 ng/mL
50 mg single, oral
DACLATASVIR plasma
Homo sapiens
16.4 ng/mL
1 mg single, oral
DACLATASVIR plasma
Homo sapiens
2816 ng/mL
200 mg single, oral
DACLATASVIR plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
11475 ng × h/mL
60 mg single, oral
DACLATASVIR plasma
Homo sapiens
15666 ng × h/mL
60 mg 1 times / day steady-state, oral
DACLATASVIR plasma
Homo sapiens
2371 ng × h/mL
10 mg single, oral
DACLATASVIR plasma
Homo sapiens
2453 ng × h/mL
10 mg 1 times / day steady-state, oral
DACLATASVIR plasma
Homo sapiens
4548 ng × h/mL
30 mg single, oral
DACLATASVIR plasma
Homo sapiens
6275 ng × h/mL
30 mg 1 times / day steady-state, oral
DACLATASVIR plasma
Homo sapiens
9680 ng × h/mL
60 mg 1 times / day steady-state, oral
DACLATASVIR plasma
Homo sapiens
13471 ng × h/mL
50 mg single, oral
DACLATASVIR plasma
Homo sapiens
162 ng × h/mL
1 mg single, oral
DACLATASVIR plasma
Homo sapiens
31793 ng × h/mL
200 mg single, oral
DACLATASVIR plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
13.5 h
60 mg 1 times / day steady-state, oral
DACLATASVIR plasma
Homo sapiens
13.5 h
50 mg single, oral
DACLATASVIR plasma
Homo sapiens
9.83 h
1 mg single, oral
DACLATASVIR plasma
Homo sapiens
11 h
200 mg single, oral
DACLATASVIR plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
60 mg 1 times / day steady-state, oral
DACLATASVIR plasma
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Sample Use Guides

In Vivo Use Guide
The recommended dosage is 60 mg, taken orally, once daily in combination with sofosbuvir for 12 weeks. Drug may be taken with or without food.
Route of Administration: Oral
In Vitro Use Guide
Daclatasvir had a median EC50 value of 0.2 nM against hybrid replicons containing genotype 3a subject-derived NS5A sequences without detectable daclatasvir resistance-associated polymorphisms at NS5A amino acid positions 28, 30, 31, or 93 with a median EC50 value of 13.5 nM (range, 1.3-50 nM). Similarly, the EC50 values of daclatasvir against 3 genotype 3b and 1 genotype 3i subject-derived NS5A sequences with polymorphisms (relative to a genotype 3a reference) at positions 30 or 31 were ≥3620 nM. The median EC50 values of daclatasvir for genotypes 1a, 1b, 2, 4, and 5 subject-derived NS5A hybrid replicons were 0.008 nM (range, 0.002-2409 nM, n=40), 0.002 nM (range, 0.0007-10 nM, n=42), 16 nM (range, 0.005-60 nM, n=16), 0.025 nM (range, 0.001-158 nM, n=14), and 0.004 nM (range, 0.003-0.019 nM, n=3), respectively. The EC50 value against a single HCV genotype 6 derived replicon was 0.054 nM.
Substance Class Chemical
Record UNII
LI2427F9CI
Record Status Validated (UNII)
Record Version