DACLATASVIR DIHYDROCHLORIDE

US Previously Marketed

First approved in 2015

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C40H50N8O6.2ClH
Molecular Weight	811.797
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of DACLATASVIR DIHYDROCHLORIDE

Structure Search

SMILES

Cl.Cl.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=BVZLLUDATICXCI-JMSCDMLISA-N

InChI=1S/C40H50N8O6.2ClH/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);2*1H/t31-,32-,33-,34-;;/m0../s1

HIDE SMILES / InChI

Molecular Formula	C40H50N8O6
Molecular Weight	738.875
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206843Orig1s000lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/27643675

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 Target	Pharmacology	Condition	Potency
Nonstructural protein 5A 11 Target ID: CHEMBL3307224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27643675	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic hepatitis C virus genotype 3 infection 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206843Orig1s000lbl.pdf	Primary		Approved 8429	DAKLINZA Approved Use DAKLINZA is indicated for use with sofosbuvir, with or without ribavirin, for the treatment of patients with chronic hepatitis C virus (HCV) genotype 1 or genotype 3 infection [see Dosage and Administration (2) and Clinical Studies (14) Launch Date 1.437696E12

C_max

Value	Dose	Analyte	Population
1295 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/29353349/	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:	DACLATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1582 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29353349/	60 mg 1 times / day steady-state, oral dose: 60 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DACLATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
291 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/29353349/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	DACLATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
257 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/29353349/	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DACLATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
610 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/29353349/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	DACLATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
734 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/29353349/	30 mg 1 times / day steady-state, oral dose: 30 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DACLATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
148 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/206843s006lbl.pdf	60 mg 1 times / day steady-state, oral dose: 60 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DACLATASVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1226 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/29353349/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	DACLATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
16.4 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/29353349/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	DACLATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2816 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/29353349/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	DACLATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
11475 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/29353349/	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:	DACLATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
15666 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29353349/	60 mg 1 times / day steady-state, oral dose: 60 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DACLATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2371 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/29353349/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	DACLATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2453 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/29353349/	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DACLATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4548 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/29353349/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	DACLATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
6275 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/29353349/	30 mg 1 times / day steady-state, oral dose: 30 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DACLATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
9680 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/206843s006lbl.pdf	60 mg 1 times / day steady-state, oral dose: 60 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DACLATASVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
13471 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/29353349/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	DACLATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
162 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/29353349/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	DACLATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
31793 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/29353349/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	DACLATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
13.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/206843s006lbl.pdf	60 mg 1 times / day steady-state, oral dose: 60 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DACLATASVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
13.5 h REVIEW https://pubmed.ncbi.nlm.nih.gov/29353349/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	DACLATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
9.83 h REVIEW https://pubmed.ncbi.nlm.nih.gov/29353349/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	DACLATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
11 h REVIEW https://pubmed.ncbi.nlm.nih.gov/29353349/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	DACLATASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/206843s006lbl.pdf	60 mg 1 times / day steady-state, oral dose: 60 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		DACLATASVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
100 mg 1 times / day multiple, oral Highest studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21837752	unhealthy, 44 years (range: 34-49 years) n = 4 Health Status: unhealthy Condition: HCV infection Age Group: 44 years (range: 34-49 years) Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/21837752	Other AEs: Headache, Diarrhea... Other AEs: Headache (25%) Diarrhea (25%) Abdominal pain (25%) Sources: https://pubmed.ncbi.nlm.nih.gov/21837752
200 mg single, oral Highest studied dose Dose: 200 mg Route: oral Route: single Dose: 200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/21837752	healthy, adult Health Status: healthy Age Group: adult Sources: https://pubmed.ncbi.nlm.nih.gov/21837752	Sources: https://pubmed.ncbi.nlm.nih.gov/21837752

AEs

AE	Significance	Dose	Population
Abdominal pain	25%	100 mg 1 times / day multiple, oral Highest studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21837752	unhealthy, 44 years (range: 34-49 years) n = 4 Health Status: unhealthy Condition: HCV infection Age Group: 44 years (range: 34-49 years) Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/21837752
Diarrhea	25%	100 mg 1 times / day multiple, oral Highest studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21837752	unhealthy, 44 years (range: 34-49 years) n = 4 Health Status: unhealthy Condition: HCV infection Age Group: 44 years (range: 34-49 years) Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/21837752
Headache	25%	100 mg 1 times / day multiple, oral Highest studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21837752	unhealthy, 44 years (range: 34-49 years) n = 4 Health Status: unhealthy Condition: HCV infection Age Group: 44 years (range: 34-49 years) Sex: M+F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/21837752

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587 inducer 781	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2B6 810 CYP2C8 911 CYP2C19 1478 OCT2 647 P-gp 1461 OATP1B1 788 OATP1B3 706 BCRP 699	P-gp 1537	CYP1A2 701 CYP2B6 547

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206843s000lbl.pdf#page=13 Page: 13.0	no [IC50 >40 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206843s000lbl.pdf#page=13 Page: 13.0	no [IC50 >40 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206843s000lbl.pdf#page=13 Page: 13.0	no [IC50 >40 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206843s000lbl.pdf#page=13 Page: 13.0	no [IC50 >40 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206843s000lbl.pdf#page=13 Page: 13.0	no [IC50 >40 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206843s000lbl.pdf#page=13 Page: 13.0	no [IC50 >40 uM]
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206843Orig1s000PharmR.pdf#page=132 Page: 132.0	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206843Orig1s000PharmR.pdf#page=132 Page: 132.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206843s000lbl.pdf#page=13 Page: 13.0	no
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206843s000lbl.pdf#page=13 Page: 13.0	yes
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206843Orig1s000PharmR.pdf#page=132; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5083780/ Page: 132.0	yes	unlikely (co-administration study) Comment: interaction between steady-state DCV and single-dose midazolam (a sensitive CYP3A4 probe) demonstrated that DCV is unlikely to impact the exposure of concomitant medications through CYP3A4-related mechanisms; midazolam exposure was minimally decreased (13%) during co-administration Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206843Orig1s000PharmR.pdf#page=132; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5083780/ Page: 132.0
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206843Orig1s000PharmR.pdf#page=132; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5083780/ Page: 132.0	yes	unlikely (co-administration study) Comment: interaction between steady-state DCV and single-dose midazolam (a sensitive CYP3A4 probe) demonstrated that DCV is unlikely to impact the exposure of concomitant medications through CYP3A4-related mechanisms; midazolam exposure was minimally decreased (13%) during co-administration Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206843Orig1s000PharmR.pdf#page=132; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5083780/ Page: 132.0
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206843s000lbl.pdf#page=13; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5083780/ Page: 13.0	yes	weak (co-administration study) Comment: The co-administration of DCV with digoxin, both agents at steady-state, resulted in a 27% increase in digoxin AUC during co-administration Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206843s000lbl.pdf#page=13; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5083780/ Page: 13.0
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206843s000lbl.pdf#page=13; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5083780/ Page: 13.0	yes	yes (co-administration study) Comment: co-administration with DCV at steady-state, single-dose rosuvastatin exposure was increased (C max, two-fold; AUC, 58% increase Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206843s000lbl.pdf#page=13; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5083780/ Page: 13.0
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206843s000lbl.pdf#page=13; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5083780/ Page: 13.0	yes	yes (co-administration study) Comment: co-administration with DCV at steady-state, single-dose rosuvastatin exposure was increased (C max, two-fold; AUC, 58% increase Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206843s000lbl.pdf#page=13; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5083780/ Page: 13.0

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206843Orig1s000PharmR.pdf#page=132; https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206843s000lbl.pdf#page=6 Page: 132.0	yes		likely (co-administration study) Comment: coadministration with CYP3A4 inhibitors/inducers are likely to affect drug concentration Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206843Orig1s000PharmR.pdf#page=132; https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206843s000lbl.pdf#page=6 Page: 132.0
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206843s000lbl.pdf#page=13 Page: 13.0	yes		no (co-administration study) Comment: cyclosporine, which inhibits multiple transporters including P-gp, did not have a clinically relevant effect on the pharmacokinetics of daclatasvir Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206843s000lbl.pdf#page=13 Page: 13.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206843Orig1s000PharmR.pdf#page=25 Page: 25.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:82977	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:82977
ChemicalBook	CB52515028	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB52515028
MolPort	MolPort-016-633-220	https://www.molport.com/shop/molecule-link/MolPort-016-633-220
MolPort	MolPort-027-720-848	https://www.molport.com/shop/molecule-link/MolPort-027-720-848
Selleck Chemicals	BMS-790052	http://www.selleckchem.com/products/BMS-790052.html
ZINC	ZINC000068204830	http://zinc15.docking.org/substances/ZINC000068204830
eMolecules	32176628	https://www.emolecules.com/cgi-bin/more?vid=32176628

PubMed

Title	Date	PubMed
		252160722
Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect.	2010 May 6	20410884
Resistance analysis of the hepatitis C virus NS5A inhibitor BMS-790052 in an in vitro replicon system.	2010 Sep	20585111
Colony-forming assays reveal enhanced suppression of hepatitis C virus replication using combinations of direct-acting antivirals.	2011 Jun	21473883
Differential efficacy of protease inhibitors against HCV genotypes 2a, 3a, 5a, and 6a NS3/4A protease recombinant viruses.	2011 Sep	21699793
Inhibition of hepatitis C virus NS5A by fluoro-olefin based γ-turn mimetics.	2012 Apr 15	22425564
In vitro activity of BMS-790052 on hepatitis C virus genotype 4 NS5A.	2012 Mar	22203595
Synthesis and biological evaluation of new potent and selective HCV NS5A inhibitors.	2012 May 15	22507961
Synthesis and evaluation of non-dimeric HCV NS5A inhibitors.	2013 Apr 1	23466233
In vitro efficacy of approved and experimental antivirals against novel genotype 3 hepatitis C virus subgenomic replicons.	2013 Nov	24013001
Characterizations of HCV NS5A replication complex inhibitors.	2013 Sep	23896639
Inhibition of hepatitis C virus replication by GS-6620, a potent C-nucleoside monophosphate prodrug.	2014	24419349
Pharmacological disruption of hepatitis C NS5A protein intra- and intermolecular conformations.	2014 Feb	23997183
The combination of alisporivir plus an NS5A inhibitor provides additive to synergistic anti-hepatitis C virus activity without detectable cross-resistance.	2014 Jun	24687498
Hepatitis C virus NS5A replication complex inhibitors: the discovery of daclatasvir.	2014 Mar 13	24521299
Novel spiroketal pyrrolidine GSK2336805 potently inhibits key hepatitis C virus genotype 1b mutants: from lead to clinical compound.	2014 Mar 13	24568313
Changing the face of hepatitis C management - the design and development of sofosbuvir.	2015	25987834
Interferon-free therapy for hepatitis C: The hurdles amid a golden era.	2015 Sep	25937625

Patents

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 Created by `admin` on `Fri Dec 15 20:15:01 UTC 2023` Edited by `admin` on `Fri Dec 15 20:15:01 UTC 2023`
Record UNII	50ZO25C11D
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DACLATASVIR DIHYDROCHLORIDE

Official Name

English

CARBAMIC ACID, N,N'-((1,1'-BIPHENYL)-4,4'-DIYLBIS(1H-IMIDAZOLE-5,2-DIYL-(2S)-2,1-PYRROLIDINEDIYL((1S)-1-(1-METHYLETHYL)-2-OXO-2,1-ETHANEDIYL)))BIS-, C,C'-DIMETHYL ESTER, HYDROCHLORIDE (1:2)

Common Name

English

METHYL N-((2S)-1-((2S)-2-(5-(4-(4'-(2-((2S)-1-((2S)-2-(METHOXYCARBONYLAMINO)-3-METHYLBUTANOYL)PYRROLIDIN-2-YL)-1H-IMIDAZOL-5-YL)PHENYL)PHENYL)-1H-IMIDAZOL-2-YL)PYRROLIDIN-1-YL)-3-METHYL-1-OXOBUTAN-2-YL)CARBAMATE DIHYDROCHLORIDE

Common Name

English

DACLATASVIR DIHYDROCHLORIDE [ORANGE BOOK]

Common Name

English

DAKLINZA

Brand Name

English

Daclatasvir dihydrochloride [WHO-DD]

Common Name

English

DIMETHYL N,N'-(BIPHENYL-4,4'-DIYLBIS(1H-IMIDAZOLE-5,2-DIYL-((2S)-PYRROLIDINE-2,1- DIYL)((1S)-1-(1-METHYLETHYL)-2-OXOETHANE-2,1-DIYL)))DICARBAMATE DIHYDROCHLORIDE

Common Name

English

BMS-790052-05

Code

English

DACLATASVIR HYDROCHLORIDE

Official Name

English

DACLATASVIR DIHYDROCHLORIDE [USAN]

Common Name

English

DACLATASVIR DIHYDROCHLORIDE [MI]

Common Name

English

DACLATASVIR HYDROCHLORIDE [JAN]

Common Name

English

BMS 790052-05

Code

English

Classification Tree Code System Code

EMA ASSESSMENT REPORTS

DAKLINZA (AUTHORIZED: HEPATITIS C, CHRONIC)