Grazoprevir hydrate (MK-5172 hydrate) is a selective inhibitor of Hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants, with K_is of 0.01 nM (gt1b), 0.01 nM (gt1a), 0.08 nM (gt2a), 0.15 nM (gt2b), 0.90 nM (gt3a), respectively. Grazoprevir hydrate inhibits SARS-CoV-2 3CL activity.

Solid

Ki: 0.01±<0.01 nM (gt1b), 0.01±0.01 nM (gt1a), 0.08±0.02 nM (gt2a), 0.15±0.06 nM (gt2b), 0.90±0.2 nM (gt3a)

In biochemical assays, Grazoprevir (MK-5172) is effective against a panel of major genotypes and variants engineered with common resistant mutations, with K_i of 0.01±<0.01 nM (gt1b), 0.01±0.01 nM (gt1a), 0.08±0.02 nM (gt2a), 0.15±0.06 nM (gt2b), 0.90±0.2 nM (gt3a), 0.07±0.01 nM (gt1b), 0.14±0.03 nM (gt1b), 0.30±0.04 nM (gt1b), 5.3±0.9 nM (gt1b), and 12±2 nM (gt1b), respectively. In the replicon assay, Grazoprevir demonstrates subnanomolar to low-nanomolar EC₅₀s against genotypes 1a, 1b, and 2a, with EC₅₀s of 0.5±0.1 nM, 2±1 nM, and 2±1 nM for gt1b, gt1a, and gt2a, respectively. Grazoprevir is potent against a panel of HCV replication mutants NS5A (Y93H) (EC₅₀=0.7±0.3 nM), NS5B nucleosides (S282T) (EC₅₀=0.3±0.1 nM), and NS5B (C316Y) (EC₅₀=0.4±0.2). Grazoprevir (MK-5172) maintains the excellent potency against the gt 3a enzyme as well as a broad panel of mutant enzymes, has excellent potency in the replicon system [gt1b IC₅₀(50% NHS)=7.4 nM; gt1a IC₅₀(40% NHS)=7 nM], and shows excellent rat liver exposure.

Medlife has not independently confirmed the accuracy of these methods. They are for reference only.

Grazoprevir (MK-5172) demonstrates efficacy in vivo against chronic-HCV-infected chimpanzees. When dosed to dogs, Grazoprevir (MK-5172) shows low clearance of 5 mL/min/kg and a 3 h half-life after iv dosing and has good plasma exposure (AUC=0.4 μM h) after a 1 mg/kg oral dose. Dog liver biopsy studies showed that the liver concentration of Grazoprevir after the 1 mg/kg oral dose is 1.4 μM at the 24 h time point. Similar to its behavior in rats, Grazoprevir demonstrates effective partitioning into liver tissue and maintains high liver concentration, relative to potency, 24 h after oral dosing in dogs.

Medlife has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature or refrigerated transportation.

• [1]. Steven Harper , John A. McCauley , Michael T. Discovery of MK-5172, a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor. ACS Med. Chem. Lett., 2012, 3 (4), pp 332-336

  [2]. Summa V, Ludmerer SW, McCauley JA, MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants. Antimicrob Agents Chemother. 2012 Aug;56(8):4161-7.  [Information]

  [3]. Qi Sun, et al. Bardoxolone and bardoxolone methyl, two Nrf2 activators in clinical trials, inhibit SARS-CoV-2 replication and its 3C-like protease. Signal Transduct Target Ther. 2021 May 29;6(1):212.  [Information]

产品不同，其溶解度不同。建议根据产品选择合适的溶剂配制储备溶液；配成溶液后，建议分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，建议在 6 个月内使用，-20°C 储存时，建议在 1 个月内使用。