Daclatasvir dihydrochlorideProduct ingredient for Daclatasvir
- Name
- Daclatasvir dihydrochloride
- Drug Entry
- Daclatasvir
Daclatasvir is a direct-acting antiviral agent against Hepatitis C Virus (HCV) used for the treatment of chronic HCV genotype 1 and 3 infection. It is marketed under the name DAKLINZA and is contained in daily oral tablets as the hydrochloride salt form . Hepatitis C is an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients 8. Daclatasvir was the first drug with demonstrated safety and therapeutic efficacy in treating HCV genotype 3 without the need for co-administration of interferon or Ribavirin. It exerts its antiviral action by preventing RNA replication and virion assembly via 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. Daclatasvir is shown to target both the cis- and trans-acting functions of NS5A and disrupts the function of new HCV replication complexes by modulating the NS5A phosphorylation status 3. The most common critical NS5A amino acid substitutions that led to reduced susceptibility to daclatasvir therapy occured at position Q30 (Q30H/K/R) and M28 in genotype 1a patients and Y93H in genotype 3 patients.
According to 2017 American Association for the Study of Liver Diseases (AASLD), 60mg of daclatasvir is recommended with 400mg Sofosbuvir for genotype 1a/b patients with or without cirrhosis as second-line therapy. The same dosing regimen can be used as first-line therapy in patients with genotype 3 without cirrhosis and second-line therapy in genotype 3 patients with compensated cirrhosis. Combination therapies that include daclatasir can be used for challenging-to-treat patients who have HIV-1 coinfection, advanced cirrhosis, or post-liver transplant recurrence of HCV 9. The therapy is intended to cure or achieve a sustained virologic response (SVR12), after 12 weeks of daily therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality 6.
Daclatasvir was FDA-approved in July 2015 for use with Sofosbuvir (Sovaldi) with or without Ribavirin to treat HCV genotype 1 and 3 infections. The SVR12 in HCV genotype 1a-infected treatment-naïve subjects without and with cirrhosis undergoing daclatasvir and Sofosbuvir therapy were 88% and 99%, respectively Label. The same dosing regimen in treatment-naïve patients with HCV genotype 3 infection with or without cirrhosis achieved SVR12 rates of 71% and 98%, respectively Label.
- Accession Number
- DBSALT001166
- Structure
- Synonyms
- Daclatasvir diHCl
- UNII
- 50ZO25C11D
- CAS Number
- 1009119-65-6
- Weight
- Average: 811.81
Monoisotopic: 810.3386868 - Chemical Formula
- C40H52Cl2N8O6
- InChI Key
- BVZLLUDATICXCI-JMSCDMLISA-N
- InChI
- 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
- IUPAC Name
- (2S)-2-{[hydroxy(methoxy)methylidene]amino}-1-[(2S)-2-[5-(4'-{2-[(2S)-1-[(2S)-2-{[hydroxy(methoxy)methylidene]amino}-3-methylbutanoyl]pyrrolidin-2-yl]-1H-imidazol-5-yl}-[1,1'-biphenyl]-4-yl)-1H-imidazol-2-yl]pyrrolidin-1-yl]-3-methylbutan-1-one dihydrochloride
- SMILES
- Cl.Cl.[H][C@](N=C(O)OC)(C(C)C)C(=O)N1CCC[C@@]1([H])C1=NC=C(N1)C1=CC=C(C=C1)C1=CC=C(C=C1)C1=CN=C(N1)[C@]1([H])CCCN1C(=O)[C@@]([H])(N=C(O)OC)C(C)C
- External Links
- ChemSpider
- 28637853
- ChEBI
- 83800
- ChEMBL
- CHEMBL2303621
- Wikipedia
- Daclatasvir
- Predicted Properties
Property Value Source Water Solubility 0.00283 mg/mL ALOGPS logP 4.74 ALOGPS logP 3.47 Chemaxon logS -5.4 ALOGPS pKa (Strongest Acidic) 3.82 Chemaxon pKa (Strongest Basic) 6.09 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 10 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 181.62 Å2 Chemaxon Rotatable Bond Count 13 Chemaxon Refractivity 203.4 m3·mol-1 Chemaxon Polarizability 83.5 Å3 Chemaxon Number of Rings 6 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon