Faldaprevir
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MedKoo CAT#: 326999

CAS#: 801283-95-4 (free acid)

Description: 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.


Chemical Structure

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Faldaprevir
CAS# 801283-95-4 (free acid)

Theoretical Analysis

MedKoo Cat#: 326999
Name: Faldaprevir
CAS#: 801283-95-4 (free acid)
Chemical Formula: C40H49BrN6O9S
Exact Mass: 868.25
Molecular Weight: 869.829
Elemental Analysis: C, 55.23; H, 5.68; Br, 9.19; N, 9.66; O, 16.55; S, 3.69

Price and Availability

Size Price Availability Quantity
1mg USD 150 Ready to ship
5mg USD 550 Ready to ship
10mg USD 950 Ready to ship
25mg USD 1650 Ready to ship
50mg USD 2650 Ready to ship
100mg USD 4650 Ready to ship
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Related CAS #: 1215856-44-2 (sodium)   801283-95-4 (free acid)    

Synonym: Faldaprevir; BI-201335; BI 201335; BI201335.

IUPAC/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

InChi Key: LLGDPTDZOVKFDU-XUHJSTDZSA-N

InChi Code: 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

SMILES Code: O=C([C@]1(NC([C@H]2N(C([C@@H](NC(OC3CCCC3)=O)C(C)(C)C)=O)C[C@H](OC4=CC(C5=CSC(NC(C(C)C)=O)=N5)=NC6=C(Br)C(OC)=CC=C46)C2)=O)[C@H](C=C)C1)O

Appearance: Solid powder

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

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target: Faldaprevir inhibits P-glycoprotein, CYP3A4, and UDP-glucuronosyltransferase 1A1.
In vitro activity: 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 activity: 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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 0.0 0.00

Preparing Stock Solutions

The following data is based on the product molecular weight 869.83 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. White PW, Llinàs-Brunet M, Amad M, Bethell RC, Bolger G, Cordingley MG, Duan J, Garneau M, Lagacé L, Thibeault D, Kukolj G. Preclinical characterization of BI 201335, a C-terminal carboxylic acid inhibitor of the hepatitis C virus NS3-NS4A protease. Antimicrob Agents Chemother. 2010 Nov;54(11):4611-8. doi: 10.1128/AAC.00787-10. Epub 2010 Sep 7. PMID: 20823284; PMCID: PMC2976164. 2. Gammeltoft KA, Zhou Y, Duarte Hernandez CR, Galli A, Offersgaard A, Costa R, Pham LV, Fahnøe U, Feng S, Scheel TKH, Ramirez S, Bukh J, Gottwein JM. Hepatitis C Virus Protease Inhibitors Show Differential Efficacy and Interactions with Remdesivir for Treatment of SARS-CoV-2 In Vitro. Antimicrob Agents Chemother. 2021 Aug 17;65(9):e0268020. doi: 10.1128/AAC.02680-20. Epub 2021 Aug 17. PMID: 34097489; PMCID: PMC8370243. 3. Chen L, George RS, Norris SH, Mao Y, Philip E, Wang LQ, Wu D, Potchoiba MJ. Biotransformation and mass balance of faldaprevir, a hepatitis C NS3/NS4 protease inhibitor in rats. Xenobiotica. 2014 Nov;44(11):1014-25. doi: 10.3109/00498254.2014.920116. Epub 2014 May 15. PMID: 24831541.
In vitro protocol: 1. White PW, Llinàs-Brunet M, Amad M, Bethell RC, Bolger G, Cordingley MG, Duan J, Garneau M, Lagacé L, Thibeault D, Kukolj G. Preclinical characterization of BI 201335, a C-terminal carboxylic acid inhibitor of the hepatitis C virus NS3-NS4A protease. Antimicrob Agents Chemother. 2010 Nov;54(11):4611-8. doi: 10.1128/AAC.00787-10. Epub 2010 Sep 7. PMID: 20823284; PMCID: PMC2976164. 2. Gammeltoft KA, Zhou Y, Duarte Hernandez CR, Galli A, Offersgaard A, Costa R, Pham LV, Fahnøe U, Feng S, Scheel TKH, Ramirez S, Bukh J, Gottwein JM. Hepatitis C Virus Protease Inhibitors Show Differential Efficacy and Interactions with Remdesivir for Treatment of SARS-CoV-2 In Vitro. Antimicrob Agents Chemother. 2021 Aug 17;65(9):e0268020. doi: 10.1128/AAC.02680-20. Epub 2021 Aug 17. PMID: 34097489; PMCID: PMC8370243.
In vivo protocol: 1. Chen L, George RS, Norris SH, Mao Y, Philip E, Wang LQ, Wu D, Potchoiba MJ. Biotransformation and mass balance of faldaprevir, a hepatitis C NS3/NS4 protease inhibitor in rats. Xenobiotica. 2014 Nov;44(11):1014-25. doi: 10.3109/00498254.2014.920116. Epub 2014 May 15. PMID: 24831541. 2. White PW, Llinàs-Brunet M, Amad M, Bethell RC, Bolger G, Cordingley MG, Duan J, Garneau M, Lagacé L, Thibeault D, Kukolj G. Preclinical characterization of BI 201335, a C-terminal carboxylic acid inhibitor of the hepatitis C virus NS3-NS4A protease. Antimicrob Agents Chemother. 2010 Nov;54(11):4611-8. doi: 10.1128/AAC.00787-10. Epub 2010 Sep 7. PMID: 20823284; PMCID: PMC2976164.

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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: Gonnella NC, Busacca CA, Zhang L, Saha A, Wu JP, Li G, Davis M, Offerdahl T, Jones PJ, Herfurth L, Reddig T, Wagner K, Niemann M, Werthmann U, Grupe J, Roos H, Reckzügel G, Ding A. Structure Elucidation of Poly-Faldaprevir: Polymer Backbone Solved Using Solid-State and Solution Nuclear Magnetic Resonance Spectroscopy. J Pharm Sci. 2016 Jun;105(6):1881-90. doi: 10.1016/j.xphs.2016.03.017. PubMed PMID: 27238486.

4: Nishiguchi S, Urano Y, Suzaki K, Taniguchi A, Scherer J, Berger KL, Quinson AM, Stern JO, Omata M. Safety and efficacy of faldaprevir in combination with pegylated interferon α-2b and ribavirin in Japanese patients with genotype-1 chronic hepatitis C virus infection. Hepatol Res. 2016 May 6. doi: 10.1111/hepr.12741. [Epub ahead of print] PubMed PMID: 27153246.

5: 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.

6: Jensen DM, Asselah T, Dieterich D, Foster GR, Sulkowski MS, Zeuzem S, Mantry P, Yoshida EM, Moreno C, Ouzan D, Wright M, Morano LE, Buynak R, Bourlière M, Hassanein T, Nishiguchi S, Kao JH, Omata M, Paik SW, Wong DK, Tam E, Kaita K, Feinman SV, Stern JO, Scherer J, Quinson AM, Voss F, Gallivan JP, Böcher WO, Ferenci P. Faldaprevir, pegylated interferon, and ribavirin for treatment-naïve HCV genotype-1: pooled analysis of two phase 3 trials. Ann Hepatol. 2016 May-Jun;15(3):333-49. doi: 10.5604/16652681.1198803. PubMed PMID: 27049487.

7: 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.

8: Asselah T, Zeuzem S, Soriano V, Bronowicki JP, Lohse AW, Müllhaupt B, Schuchmann M, Bourlière M, Buti M, Roberts SK, Gane EJ, Stern JO, Voss F, Baum P, Gallivan JP, Böcher WO, Mensa FJ. ITPA Genotypes Predict Anemia but Do Not Affect Virological Response with Interferon-Free Faldaprevir, Deleobuvir, and Ribavirin for HCV Infection. PLoS One. 2015 Dec 9;10(12):e0144004. doi: 10.1371/journal.pone.0144004. eCollection 2015. PubMed PMID: 26650626; PubMed Central PMCID: PMC4674133.

9: Foster GR, Ferenci P, Asselah T, Mantry P, Dufour JF, Bourlière M, Forton D, Maevskaya M, Wright D, Yoshida EM, García-Samaniego J, Oliveira C, Wright M, Warner N, Sha N, Quinson AM, Stern JO. Open-label study of faldaprevir plus peginterferon and ribavirin in hepatitis C virus genotype 1-infected patients who failed placebo plus peginterferon and ribavirin. J Viral Hepat. 2016 Mar;23(3):227-31. doi: 10.1111/jvh.12485. Epub 2015 Nov 17. PubMed PMID: 26572686.

10: Berger KL, Scherer J, Ranga M, Sha N, Stern JO, Quinson AM, Kukolj G. Baseline Polymorphisms and Emergence of Drug Resistance in the NS3/4A Protease of Hepatitis C Virus Genotype 1 following Treatment with Faldaprevir and Pegylated Interferon Alpha 2a/Ribavirin in Phase 2 and Phase 3 Studies. Antimicrob Agents Chemother. 2015 Oct;59(10):6017-25. doi: 10.1128/AAC.00932-15. Epub 2015 Jul 20. PubMed PMID: 26195509; PubMed Central PMCID: PMC4576130.

11: Campagna D, Demma S. Faldaprevir for the treatment of hepatitis C. Drugs Today (Barc). 2015 May;51(5):289-301. doi: 10.1358/dot.2015.51.5.2321008. Review. PubMed PMID: 26097902.

12: Yatsuhashi H, Kodani N, Ugai H, Omata M. Open-label phase 2 study of faldaprevir, deleobuvir and ribavirin in Japanese treatment-naive patients with chronic hepatitis C virus genotype 1 infection. Hepatol Res. 2016 Mar;46(3):E189-93. doi: 10.1111/hepr.12535. Epub 2015 Jun 18. PubMed PMID: 25991083.

13: Kanda T, Yokosuka O, Omata M. Faldaprevir for the treatment of hepatitis C. Int J Mol Sci. 2015 Mar 4;16(3):4985-96. doi: 10.3390/ijms16034985. Review. PubMed PMID: 25749475; PubMed Central PMCID: PMC4394460.

14: Dieterich D, Nelson M, Soriano V, Arastéh K, Guardiola JM, Rockstroh JK, Bhagani S, Laguno M, Tural C, Ingiliz P, Jain MK, Stern JO, Manero M, Vinisko R, Kort J; STARTVerso4 study group. Faldaprevir and pegylated interferon α-2a/ribavirin in individuals co-infected with hepatitis C virus genotype-1 and HIV. AIDS. 2015 Mar 13;29(5):571-81. doi: 10.1097/QAD.0000000000000579. PubMed PMID: 25710287.

15: Agarwal K, Barnabas A. Faldaprevir for the treatment of genotype-1 hepatitis C virus. Expert Rev Gastroenterol Hepatol. 2015 Mar;9(3):277-88. doi: 10.1586/17474124.2015.1001742. Epub 2015 Jan 29. Review. PubMed PMID: 25633983.

16: Dieterich D, Nelson M, Soriano V, Arastéh K, Guardiola JM, Rockstroh JK, Bhagani S, Laguno M, Tural C, Ingiliz P, Jain MK, Stern JO, Manero M, Vinisko R, Kort J; the STARTVerso4 study group. STARTVerso4: faldaprevir and pegylated interferon α-2a/ribavirin in individuals co-infected with hepatitis C virus genotype-1 and HIV. AIDS. 2015 Jan 21. [Epub ahead of print] PubMed PMID: 25611148.

17: Ferenci P, Asselah T, Foster GR, Zeuzem S, Sarrazin C, Moreno C, Ouzan D, Maevskaya M, Calinas F, Morano LE, Crespo J, Dufour JF, Bourlière M, Agarwal K, Forton D, Schuchmann M, Zehnter E, Nishiguchi S, Omata M, Kukolj G, Datsenko Y, Garcia M, Scherer J, Quinson AM, Stern JO; STARTVerso1 Study Group. STARTVerso1: A randomized trial of faldaprevir plus pegylated interferon/ribavirin for chronic HCV genotype-1 infection. J Hepatol. 2015 Jun;62(6):1246-55. doi: 10.1016/j.jhep.2014.12.024. Epub 2015 Jan 2. PubMed PMID: 25559324.

18: Zeuzem S, Soriano V, Asselah T, Gane EJ, Bronowicki JP, Angus P, Lohse AW, Stickel F, Müllhaupt B, Roberts S, Schuchmann M, Manns M, Bourlière M, Buti M, Stern JO, Gallivan JP, Voss F, Sabo JP, Böcher W, Mensa FJ; SOUND-C2 Study Group. Efficacy and safety of faldaprevir, deleobuvir, and ribavirin in treatment-naive patients with chronic hepatitis C virus infection and advanced liver fibrosis or cirrhosis. Antimicrob Agents Chemother. 2015 Feb;59(2):1282-91. doi: 10.1128/AAC.04383-14. Epub 2014 Dec 15. PubMed PMID: 25512403; PubMed Central PMCID: PMC4335863.

19: Sabo JP, Kort J, Ballow C, Kashuba AD, Haschke M, Battegay M, Girlich B, Ting N, Lang B, Zhang W, Cooper C, O'Brien D, Seibert E, Chan TS, Tweedie D, Li Y. Interactions of the hepatitis C virus protease inhibitor faldaprevir with cytochrome P450 enzymes: in vitro and in vivo correlation. J Clin Pharmacol. 2015 Apr;55(4):467-77. doi: 10.1002/jcph.436. Epub 2015 Jan 14. PubMed PMID: 25449227.

20: Sabo JP, Lang B, Elgadi M, Huang F. Effect of the hepatitis C virus protease inhibitor faldaprevir on the pharmacokinetics of an oral contraceptive containing ethinylestradiol and levonorgestrel in healthy female volunteers. Antimicrob Agents Chemother. 2015 Jan;59(1):514-9. doi: 10.1128/AAC.03589-14. Epub 2014 Nov 10. PubMed PMID: 25385099; PubMed Central PMCID: PMC4291440.