Telaprevir
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MedKoo CAT#: 315233

CAS#: 402957-28-2

Description: Telaprevir (VX-950), marketed under the brand names Incivek and Incivo, is a pharmaceutical drug for the treatment of hepatitis C co-developed by Vertex Pharmaceuticals and Johnson & Johnson. It is a member of a class of antiviral drugs known as protease inhibitors. Specifically, telaprevir inhibits the hepatitis C viral enzyme NS3.4A serine protease. Telaprevir is only indicated for use against hepatitis C genotype 1 viral infections and has not been proven to have an effect on or being safe when used for other genotypes of the virus. The standard therapy of pegylated interferon and ribavirin is less effective on genotype 1.


Chemical Structure

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Telaprevir
CAS# 402957-28-2

Theoretical Analysis

MedKoo Cat#: 315233
Name: Telaprevir
CAS#: 402957-28-2
Chemical Formula: C36H53N7O6
Exact Mass: 679.40573
Molecular Weight: 679.85
Elemental Analysis: C, 63.60; H, 7.86; N, 14.42; O, 14.12

Price and Availability

Size Price Availability Quantity
25.0mg USD 150.0 Ready to ship
50.0mg USD 250.0 Ready to ship
100.0mg USD 450.0 Ready to ship
200.0mg USD 750.0 Ready to ship
500.0mg USD 1250.0 Ready to ship
1.0g USD 1950.0 Ready to ship
2.0g USD 2950.0 Ready to ship
5.0g USD 4950.0 Ready to ship
10.0g USD 8950.0 Ready to ship
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Synonym: VX950; VX950; VX 950; Incivek; Incivo; Telaprevir;

IUPAC/Chemical Name: (3S,3aS,6aR)-2-[(2S)-2-[[(2S)-2-cyclohexyl-2-(pyrazine-2-carbonylamino)acetyl]amino]-3,3-dimethylbutanoyl]-N-[(3S)-1-(cyclopropylamino)-1,2-dioxohexan-3-yl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-3-carboxamide

InChi Key: BBAWEDCPNXPBQM-GDEBMMAJSA-N

InChi Code: InChI=1S/C36H53N7O6/c1-5-10-25(29(44)34(48)39-23-15-16-23)40-33(47)28-24-14-9-13-22(24)20-43(28)35(49)30(36(2,3)4)42-32(46)27(21-11-7-6-8-12-21)41-31(45)26-19-37-17-18-38-26/h17-19,21-25,27-28,30H,5-16,20H2,1-4H3,(H,39,48)(H,40,47)(H,41,45)(H,42,46)/t22-,24-,25-,27-,28-,30+/m0/s1

SMILES Code: O=C([C@@H]1[C@](CCC2)([H])[C@]2([H])CN1C([C@@H](NC([C@H](C3CCCCC3)NC(C4=NC=CN=C4)=O)=O)C(C)(C)C)=O)N[C@@H](CCC)C(C(NC5CC5)=O)=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 (50mg/mL).

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

Biological target: Telaprevir (VX-950) is a highly selective, reversible, and potent peptidomimetic that inhibits SARS-CoV-2 3CLpro activity as well as HCV NS3-4A protease; the steady-state inhibitory constant (Ki) of Telaprevir is 7 nM against a genotype 1 (H strain) NS3 protease domain plus a NS4A cofactor peptide.
In vitro activity: The anti-HCV activity of VX-950 (Fig.1) was examined in Con1 (genotype 1b) subgenomic HCV replicon cells. In this system, inhibition of HCV NS3-4A protease by VX-950 was expected to block viral polyprotein processing and subsequently decrease viral RNA replication and total HCV RNA levels in the replicon cells. As shown in Fig.2, VX-950 reduced HCV RNA levels in a time- and dose-dependent manner. The IC50s following a 24-, 48-, 72-, and 120-h incubation with VX-950 were determined to be 0.574, 0.488, 0.210, and 0.139 μM, respectively, indicating an increase in inhibitory effects with time. These results show that the IC50 declined as the culture time increased. Following three independent experiments using the 48-h incubation in the presence of 2% FBS, the average (±standard deviation [SD]) IC50 of VX-950 was determined to be 0.354 ± 0.035 μM, and the average (±SD) IC90 was 0.830 ± 0.190 μM. After a 48-h incubation with VX-950, no significant cytotoxicity, as evaluated in an MTS-based cell viability assay, was observed in the replicon cells. The average CC50 (±SD) of VX-950 in HCV replicon cells was 83 ± 27 μM, which resulted in a selective index, i.e., the n-fold value of CC50 over IC50, of 230 ± 59. In both parental Huh-7 and HepG2 cell lines, no significant cytotoxicity was observed after a 48-h incubation with up to 30 μM VX-950 in the presence of DMEM plus 2% FBS. Reference: Antimicrob Agents Chemother. 2006 May; 50(5): 1813–1822. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1472227/
In vivo activity: The ability of VX-950 to inhibit HCV protease-dependent cleavage and subsequent secretion of SEAP from the liver into the blood was tested in mice. Five groups of 6-week-old SCID mice (6 animals per group) were injected with 109 IFU per mouse of recombinant adenovirus Ad-WT-HCVpro-SEAP through the tail vein. Each group of mice was given two oral administrations of VX950 at one of the following doses: 10, 25, 75, 150, or 300 mg/kg. As shown in Fig.6B, there was an ∼5-fold reduction of serum SEAP activity in mice dosed with VX-950 at either 10 or 25 mg/kg, which had an average value (±SEM) of 18.7 ± 8.3% or 18.4 ± 5.4%, respectively, compared to those administered vehicle (100 ± 28%). These data demonstrated that VX-950 was able to inhibit the HCV NS3-4A serine protease activity in mouse liver and block cleavage and subsequent secretion of SEAP into blood circulation in these mice. As shown in Fig.6C, there was a dose-dependent increase in VX-950 exposure at 1 h postdosing in both liver and plasma. At the lowest dose tested (10 mg/kg), the level of VX-950 in the mouse liver 1 h after oral dosing was 3.86 ± 0.18 μg/g. Assuming the density of liver to be 1 g/ml, this liver concentration of VX-950 at 1 h corresponded to 5.68 ± 0.27 μM, which was about sixfold higher than that in the plasma (0.94 ± 0.09 μM). This liver concentration at 1 h is about 16-fold higher than the 48-h IC50 of VX-950 (354 nM) in HCV replicon cells. At doses higher than 10 mg/kg, the ratio of liver-to-plasma exposure of VX-950 1 h after dosing ranged from 11- to 16-fold. In mice and rats, VX-950 achieved excellent exposure in the liver, which is the primary organ of HCV infection, suggesting that adequate exposures of the drug in humans can be achieved. Reference: Antimicrob Agents Chemother. 2006 Mar; 50(3): 899–909. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1426435/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 64.0 94.14

Preparing Stock Solutions

The following data is based on the product molecular weight 679.85 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. Jiang M, Mani N, Lin C, Ardzinski A, Nelson M, Reagan D, Bartels D, Zhou Y, Nicolas O, Rao BG, Müh U, Hanzelka B, Tigges A, Rijnbrand R, Kieffer TL. In vitro phenotypic characterization of hepatitis C virus NS3 protease variants observed in clinical studies of telaprevir. Antimicrob Agents Chemother. 2013 Dec;57(12):6236-45. doi: 10.1128/AAC.01578-13. Epub 2013 Oct 7. PMID: 24100495; PMCID: PMC3837892. 2. Lin K, Perni RB, Kwong AD, Lin C. VX-950, a novel hepatitis C virus (HCV) NS3-4A protease inhibitor, exhibits potent antiviral activities in HCv replicon cells. Antimicrob Agents Chemother. 2006 May;50(5):1813-22. doi: 10.1128/AAC.50.5.1813-1822.2006. PMID: 16641454; PMCID: PMC1472227. 3. Perni RB, Almquist SJ, Byrn RA, Chandorkar G, Chaturvedi PR, Courtney LF, Decker CJ, Dinehart K, Gates CA, Harbeson SL, Heiser A, Kalkeri G, Kolaczkowski E, Lin K, Luong YP, Rao BG, Taylor WP, Thomson JA, Tung RD, Wei Y, Kwong AD, Lin C. Preclinical profile of VX-950, a potent, selective, and orally bioavailable inhibitor of hepatitis C virus NS3-4A serine protease. Antimicrob Agents Chemother. 2006 Mar;50(3):899-909. doi: 10.1128/AAC.50.3.899-909.2006. PMID: 16495249; PMCID: PMC1426435.
In vitro protocol: 1. Jiang M, Mani N, Lin C, Ardzinski A, Nelson M, Reagan D, Bartels D, Zhou Y, Nicolas O, Rao BG, Müh U, Hanzelka B, Tigges A, Rijnbrand R, Kieffer TL. In vitro phenotypic characterization of hepatitis C virus NS3 protease variants observed in clinical studies of telaprevir. Antimicrob Agents Chemother. 2013 Dec;57(12):6236-45. doi: 10.1128/AAC.01578-13. Epub 2013 Oct 7. PMID: 24100495; PMCID: PMC3837892. 2. Lin K, Perni RB, Kwong AD, Lin C. VX-950, a novel hepatitis C virus (HCV) NS3-4A protease inhibitor, exhibits potent antiviral activities in HCv replicon cells. Antimicrob Agents Chemother. 2006 May;50(5):1813-22. doi: 10.1128/AAC.50.5.1813-1822.2006. PMID: 16641454; PMCID: PMC1472227.
In vivo protocol: 1. Perni RB, Almquist SJ, Byrn RA, Chandorkar G, Chaturvedi PR, Courtney LF, Decker CJ, Dinehart K, Gates CA, Harbeson SL, Heiser A, Kalkeri G, Kolaczkowski E, Lin K, Luong YP, Rao BG, Taylor WP, Thomson JA, Tung RD, Wei Y, Kwong AD, Lin C. Preclinical profile of VX-950, a potent, selective, and orally bioavailable inhibitor of hepatitis C virus NS3-4A serine protease. Antimicrob Agents Chemother. 2006 Mar;50(3):899-909. doi: 10.1128/AAC.50.3.899-909.2006. PMID: 16495249; PMCID: PMC1426435.

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1: Goralczyk AD, Cameron S, Amanzada A. Treatment of chronic HCV genotype 1 infection with telaprevir: a Bayesian mixed treatment comparison of fixed-length and response-guided treatment regimens in treatment-naïve and -experienced patients. BMC Gastroenterol. 2013 Oct 14;13:148. doi: 10.1186/1471-230X-13-148. Review. PubMed PMID: 24118976; PubMed Central PMCID: PMC3852825.

2: Schmutz JL, Trechot P. [Telaprevir-induced pityriasis rubra pilaris]. Ann Dermatol Venereol. 2013 May;140(5):414-5. doi: 10.1016/j.annder.2013.01.336. Epub 2013 Mar 6. Review. French. PubMed PMID: 23663723.

3: Kiang TK, Wilby KJ, Ensom MH. Telaprevir: clinical pharmacokinetics, pharmacodynamics, and drug-drug interactions. Clin Pharmacokinet. 2013 Jul;52(7):487-510. doi: 10.1007/s40262-013-0053-x. Review. PubMed PMID: 23553423.

4: Rajani AK, Ravindra BK, Dkhar SA. Telaprevir: changing the standard of care of chronic hepatitis C. J Postgrad Med. 2013 Jan-Mar;59(1):42-7. doi: 10.4103/0022-3859.109493. Review. PubMed PMID: 23525057.

5: Izquierdo-García E, Escobar-Rodríguez I. [Systematic review of new protease inhibitors interactions: telaprevir and boceprevir]. Farm Hosp. 2012 Nov-Dec;36(6):469-82. doi: 10.7399/FH.2012.36.6.47. Review. Spanish. PubMed PMID: 23461440.

6: Gu L, Chen Q, Xie J, Yan Y, Wu G, Tan J, Liang B, Chen W, Wu P, Su L, Tang N. Telaprevir for genotype 1 chronic hepatitis C: a systematic review and meta-analysis. Pharmazie. 2012 Dec;67(12):963-72. Review. PubMed PMID: 23346756.

7: van Heeswijk RP, Beumont M, Kauffman RS, Garg V. Review of drug interactions with telaprevir and antiretrovirals. Antivir Ther. 2013;18(4):553-60. doi: 10.3851/IMP2527. Epub 2013 Jan 23. Review. PubMed PMID: 23344266.

8: Jesudian AB, Jacobson IM. Optimal treatment with telaprevir for chronic HCV infection. Liver Int. 2013 Feb;33 Suppl 1:3-13. doi: 10.1111/liv.12079. Review. PubMed PMID: 23286840.

9: Nikitin IG, Gogova LM, Baikova IE, Kislyakov VA, Volynkina VM. [Telaprevir: new possibilities for antiviral treatment in patients with chronic hepatitis C]. Ter Arkh. 2012;84(11):75-80. Review. Russian. PubMed PMID: 23252254.

10: Esteban R, Buti M. Triple therapy with boceprevir or telaprevir for treatment naïve HCV patients. Best Pract Res Clin Gastroenterol. 2012 Aug;26(4):445-53. doi: 10.1016/j.bpg.2012.09.001. Review. PubMed PMID: 23199503.