Ledipasvir

Ledipasvir, also known as GS-5885; is an inhibitor of the hepatitis C virus NS5A protein and is a drug for the treatment of hepatitis C that was developed by Gilead Sciences. On October 10, 2014 the FDA approved the combination product ledipasvir 90 mg/sofosbuvir 400 mg (trade name Harvoni). The ledipasvir/sofosbuvir combination is a direct-acting antiviral agent that interferes with HCV replication and can be used to treat patients with genotypes 1a or 1b without PEG-interferon or ribavirin. (http://en.wikipedia.org/wiki/Ledipasvir)

Product information

CAS Number: 1256388-51-8

Molecular Weight: 889.00

Formula: C49H54F2N8O6

Synonym:

GS5885

GS-5885

GS 5885

Harvoni

Ledipasvir

Chemical Name: MethylN-[(2S)-1-[(6S)-6-[5-[9,9-Difluoro-7-[2-[(1S,2S,4R)-3-[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]-3-azabicyclo[2.2.1]heptan-2-yl]-3H-benzimidazol-5-yl]fluoren-2-yl]-1H-imidazol-2-yl]-5-azaspiro[2.4]heptan-5-yl]-3-methyl-1-oxobutan-2-yl]carbamate

Smiles: CC(C)[C@H](NC(=O)OC)C(=O)N1CC2(C[C@H]1C1NC(=CN=1)C1=CC3=C(C=C1)C1=CC=C(C=C1C3(F)F)C1=CC3NC(=NC=3C=C1)[C@@H]1[C@@H]3C[C@@H](CC3)N1C(=O)[C@@H](NC(=O)OC)C(C)C)CC2

InChiKey: VRTWBAAJJOHBQU-KMWAZVGDSA-N

InChi: InChI=1S/C49H54F2N8O6/c1-24(2)39(56-46(62)64-5)44(60)58-23-48(15-16-48)21-38(58)42-52-22-37(55-42)28-9-13-32-31-12-8-26(18-33(31)49(50,51)34(32)19-28)27-10-14-35-36(20-27)54-43(53-35)41-29-7-11-30(17-29)59(41)45(61)40(25(3)4)57-47(63)65-6/h8-10,12-14,18-20,22,24-25,29-30,38-41H,7,11,15-17,21,23H2,1-6H3,(H,52,55)(H,53,54)(H,56,62)(H,57,63)/t29-,30+,38-,39-,40-,41-/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Solubility (25°C) DMSO: 100 mg/mL(112.48 mM). Water: Insoluble.

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Ledipasvir has GT1a and 1b EC50 values of 31 and 4 pM, respectively, and protein-adjusted EC50 values of 210 pM (GT1a) and 27 pM (GT1b) and the intrinsic EC50 of 39 is 310 fM for GT1a and 40 fM for GT1b. Ledipasvir is highly protein-bound both in human serum and in the cell-culture medium (containing 10% BSA) of the replicon assay. Ledipasvir exhibits an EC50 value of 141 nM against the JFH/3a-NS5A replicon.

In Vivo:

Ledipasvir is remarkable not only on the basis of its high replicon potency but also on the basis of its low clearance, good bioavailability, and long half-lives in rat, dog, and monkey and low predicted clearance in human. The pharmacokinetics of Ledipasvir is measured in rats and dogs. Ledipasvir shows good half-lives (rat 1.83 ± 0.22 hr, dog 2.63 ± 0.18 hr) in plasma, low systemic clearance (CL), and moderate volumes of distribution (Vss) that are greater than total body water volume.

References:

1. Younossi ZM, Stepanova M, Marcellin P, Afdhal N, Kowdley KV, Zeuzem S, Hunt SL. Treatment with ledipasvir and sofosbuvir improves patient-reported outcomes: Results from the Ion-1, 2 and 3 clinical trials. Hepatology. 2015 Jan 27. doi: 10.1002/hep.27724. [Epub ahead of print] PubMed PMID: 25627448.
2. Younossi ZM, Park H, Saab S, Ahmed A, Dieterich D, Gordon SC. Cost-effectiveness of all-oral ledipasvir/sofosbuvir regimens in patients with chronic hepatitis C virus genotype 1 infection. Aliment Pharmacol Ther. 2015 Jan 26. doi: 10.1111/apt.13081. [Epub ahead of print] PubMed PMID: 25619871.
3. Smith MA, Chan J, Mohammad RA. Ledipasvir-Sofosbuvir: Interferon-/Ribavirin-Free Regimen for Chronic Hepatitis C Virus Infection. Ann Pharmacother. 2014 Dec 16. pii: 1060028014563952. [Epub ahead of print] Review. PubMed PMID: 25515863.
4. A combination of ledipasvir and sofosbuvir (Harvoni) for hepatitis C. Med Lett Drugs Ther. 2014 Nov 10;56(1455):111-2. PubMed PMID: 25372848.
5. A SPECIAL MEETING REVIEW EDITION: Advances in the Treatment of Hepatitis C Virus Infection from The Liver Meeting 2013: The 64th Annual Meeting of the American Association for the Study of Liver DiseasesNovember 1-5, 2013 • Washington DCSpecial Reporting on:• Simeprevir plus Sofosbuvir with or without Ribavirin Produces High SVR Rates in Genotype 1 HCV Infection• Novel Interferon- and Ribavirin-Free Regimen Results in SVR12 Rates of Over 90% in HCV Genotype 1b Infection• Studies Confirm Efficacy of Adjunctive Simeprevir in Difficult-to-Treat HCV Genotype 1 Subpopulations• All-Oral Therapy with Sofosbuvir Plus Ribavirin Produces High SVR Rates in Patients Coinfected with HCV and HIV• Faldaprevir Combined with Pegylated Interferon and Ribavirin Demonstrates High Efficacy in DifficuIt-to-Treat HCV Infection• Once Daily Sofosbuvir/Ledipasvir Combination Elicits Rapid Decline in HCV RNAPLUS Meeting Abstract Summaries With Expert Commentary by: Ira M. Jacobson, MDWeill Cornell Medical CollegeNew York, New York. Gastroenterol Hepatol (N Y). 2014 Jan;10(1 Suppl 1):1-19. PubMed PMID: 25337060; PubMed Central PMCID: PMC4201083.
6. Gentile I, Borgia G. Ledipasvir/Sofosbuvir administration achieves very high rate of viral clearance in patients with HCV genotype 1 infection without cirrhosis, regardless of ribavirin co-administration or length of treatment. Evid Based Med. 2014 Dec;19(6):223-4. doi: 10.1136/ebmed-2014-110051. Epub 2014 Jul 15. PubMed PMID: 25028605.

Products are for research use only. Not for human use.