Faldaprevir

Faldaprevir, also known as BI-201335, is a potent NS3/NS4A protease inhibitor potentially for the treatment of HCV infection. Faldaprevir is known to inhibit P-glycoprotein, CYP3A4, and UDP-glucuronosyltransferase 1A1.

Product information

CAS Number: 801283-95-4

Molecular Weight: 869.82

Formula: C40H49BrN6O9S

Chemical Name: (1R, 2S)-1-((2S, 4R)-4-((8-bromo-2-(2-isobutyramidothiazol-4-yl)-7-methoxyquinolin-4-yl)oxy)-1-((S)-2-(((cyclopentyloxy)carbonyl)amino)-3, 3-dimethylbutanoyl)pyrrolidine-2-carboxamido)-2-vinylcyclopropane-1-carboxylic acid

Smiles: CC(C)(C)[C@H](NC(=O)OC1CCCC1)C(=O)N1C[C@@H](C[C@H]1C(=O)N[C@@]1(C[C@H]1C=C)C(O)=O)OC1=CC(=NC2=C(Br)C(=CC=C21)OC)C1=CSC(NC(=O)C(C)C)=N1

InChiKey: LLGDPTDZOVKFDU-XUHJSTDZSA-N

InChi: InChI=1S/C40H49BrN6O9S/c1-8-21-17-40(21,36(51)52)46-34(49)27-15-23(18-47(27)35(50)32(39(4,5)6)44-38(53)56-22-11-9-10-12-22)55-29-16-25(26-19-57-37(43-26)45-33(48)20(2)3)42-31-24(29)13-14-28(54-7)30(31)41/h8,13-14,16,19-23,27,32H,1,9-12,15,17-18H2,2-7H3,(H,44,53)(H,46,49)(H,51,52)(H,43,45,48)/t21-,23-,27+,32-,40-/m1/s1

Technical Data

Appearance: Solid Power

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

Solubility: To be determined

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:

Inhibition of protease activity by BI 201335 was evaluated using the full-length NS3 protein coexpressed with the 54-amino-acid cofactor NS4A (NS3-NS4A). BI 201335 showed a similar level of inhibitory potency against the NS3-NS4A proteases of HCV genotypes 4a, 5a, and 6a as it did against the two genotype 1 enzymes (≤5-fold difference), but it was somewhat less potent against enzymes from HCV genotypes 2a, 2b, and 3a (20, 50, and 190-fold, relative to genotype 1a). BI 201335 also had no significant activity against the human serine and cysteine proteases elastase and cathepsin B (CatB). In vitro liver microsome stability studies revealed low metabolic clearance of <19% of hepatic blood flow (Qh) in all species tested, including humans, with the ranking order monkey > human > dog ≈ rat. BI 201335 was highly bound to human plasma proteins (99.6%), as determined by equilibrium dialysis. Reference: Antimicrob Agents Chemother. 2010 Nov;54(11):4611-8. https://pubmed.ncbi.nlm.nih.gov/20823284/

In Vivo:

The metabolism, pharmacokinetics, excretion and tissue distribution of a hepatitis C NS3/NS4 protease inhibitor, faldaprevir, were studied in rats following a single 2 mg/kg intravenous or 10 mg/kg oral administration of [(14)C]-faldaprevir. Following intravenous dosing, the terminal elimination t1/2 of plasma radioactivity was 1.75 h (males) and 1.74 h (females). Corresponding AUC0-∞, CL and Vss were 1920 and 1900 ngEq · h/mL, 18.3 and 17.7 mL/min/kg and 2.32 and 2.12 mL/kg for males and females, respectively. n intact rats, ≥90.17% dose was recovered in feces and only ≤1.08% dose was recovered in urine for both iv and oral doses. In bile cannulated rats, 54.95, 34.32 and 0.27% dose was recovered in feces, bile and urine, respectively. It was found that glucuronidation plays a major role in the metabolism of faldaprevir with minimal Phase I metabolism. Reference: Xenobiotica. 2014 Nov;44(11):1014-25. https://pubmed.ncbi.nlm.nih.gov/24831541/

References:

1. Meeprasert A, Hannongbua S, Kungwan N, Rungrotmongkol T. Effect of D168V mutation in NS3/4A HCV protease on susceptibilities of faldaprevir and danoprevir. Mol Biosyst. 2016 Oct 12. PubMed PMID: 27731877.
2. Berger KL, Sarrazin C, Nelson DR, Scherer J, Sha N, Marquis M, Côté-Martin A, Vinisko R, Stern JO, Mensa FJ, Kukolj G. Resistance Analyses of HCV NS3/4A Protease and NS5B Polymerase from Clinical Studies of Deleobuvir and Faldaprevir. PLoS One. 2016 Aug 5;11(8):e0160668. doi: 10.1371/journal.pone.0160668. eCollection 2016. PubMed PMID: 27494410; PubMed Central PMCID: PMC4975400.
3. Zeuzem S, Mantry P, Soriano V, Buynak RJ, Dufour JF, Pockros PJ, Wright D, Angus P, Buti M, Stern JO, Kadus W, Vinisko R, Böcher W, Mensa FJ. Short article: Faldaprevir, deleobuvir and ribavirin in IL28B non-CC patients with HCV genotype-1a infection included in the SOUND-C3 phase 2b study. Eur J Gastroenterol Hepatol. 2016 Aug;28(8):923-6. doi: 10.1097/MEG.0000000000000649. PubMed PMID: 27140229.
4. Wu J, Gießmann T, Lang B, Elgadi M, Huang F. Investigation of the effect of food and omeprazole on the relative bioavailability of a single oral dose of 240 mg faldaprevir, a selective inhibitor of HCV NS3/4 protease, in an open-label, randomized, three-way cross-over trial in healthy participants. J Pharm Pharmacol. 2016 Apr;68(4):459-66. doi: 10.1111/jphp.12538. Epub 2016 Mar 28. PubMed PMID: 27019158.

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