生物活性

• 描述The NS3-4A serine protease of hepatitis C virus (HCV) is essential for viral replication and therefore has been one of the most attractive targets for developing specific antiviral agents against HCV. Telaprevir is a highly selective, potent and reversible inhibitor of HCV NS3-4A protease with an IC₅₀ of 0.35 μM. Telaprevir reduced HCV RNA levels in replicon cells in a time- and dose-dependent manner. In cells incubated with 10 μM telaprevir for 24, 48, 72, or 96 h, there was a time-dependent decrease of HCV NS3 and NS5A proteins^[3]. In several animal species, Telaprevir exhibited a favorable pharmacokinetic profile with high exposure in the liver. In a recently developed HCV protease mouse model, Telaprevir (10 or 25 mg/kg) showed excellent inhibition of HCV NS3-4A protease activity in the liver^[4].
• 作用机制There was a covalent bond between the serine nucleophile of the HCV protease catalytic triad and the α-ketoamide functionality of telaprevir^[4].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01816490	HIV Hepatitis... more >> C Collapse <<	Phase 2	Completed	-	Switzerland ... more >> Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich Zurich, Switzerland, 8091 Collapse <<
  NCT01604291	-	-	Completed	-	Israel ... more >> Haemek Hospital; Gastroenterology Afula, Israel, 18101 Barzilai MC; Gastroenterology Ashkelon, Israel, 78278 Soroka Medical Center; Gastroenterology Beer Sheva, Israel, 84105 Hillel Yaffe Hospital; Gastroenterology Hadera, Israel, 38100 Rambam Medical Center; Gastroenterology - Liver Unit Haifa, Israel, 31096 Bnei-Zion Medical Center; Gastroenterology Haifa, Israel, 33394 Carmel Hospital; Liver Unit Haifa, Israel, 34362 Wolfson Hospital; Gastroenterology Unit Holon, Israel, 58100 Shaare Zedek Hospital Liver Unit; Liver Unit Jerusalem, Israel, 91031 Hadassah Hospital; Liver Unit Jerusalem, Israel, 91120 Meir Medical Center; Liver Unit Kfar Saba, Israel, 44281 Western Galilee Hospital - Nahariya Nahariya, Israel, 22100 Holy Family Medical Center; Liver Unit Nazareth, Israel Hasharon Mc; Gastroenterology Petach Tikva, Israel Beilinson-Rabin Liver Unit; Liver Unit Petah Tiqwa, Israel Sheba Medical Center; Tel Hashomer Ramat Gan, Israel, 5262100 Kaplan Medical Center; Gastroenterology Unit Rehovot, Israel, 76100 Rebecca Sieff Medical Center; Liver Unit Safed, Israel, 13110 Tel-Aviv Sourasky Medical Center; Liver Unit Tel Aviv, Israel, 6423906 Poria Hospital; Gastroenterology Tiberias, Israel Assaf Harofeh; Gastroenterology Zerifin, Israel, 6093000 Collapse <<
  NCT01508130	-	-	Completed	-	-

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• 参考文献

• [1] Lin K, Perni RB, et al. 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.

  [2] Perni RB, Almquist SJ, et al. 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.

  [3] 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

  [4] Perni RB, Almquist SJ, Byrn RA, et al. 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