Grazoprevir

Catalog No.S3728 Batch:S372801

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Technical Data

Formula

C38H50N6O9S
Molecular Weight 766.9 CAS No. 1350514-68-9
Solubility (25°C)* In vitro DMSO 100 mg/mL (130.39 mM)
Ethanol 100 mg/mL (130.39 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Grazoprevir anhydrous (MK5172) is a Hepatitis C Virus NS3/4A Protease inhibitor with IC50 values of 7pM, 4pM, and 62pM for HCV genotype 1a, 1B, and 4 respectively.
Targets
gt1b [1]
(Cell-free assay)		 gt1a [1]
(Cell-free assay)		 gt1b R155K [1]
(Cell-free assay)		 gt2a [1]
(Cell-free assay)		 gt1b D168V [1]
(Cell-free assay)		 View More
0.01 nM(Ki) 0.01 nM(Ki) 0.07 nM(Ki) 0.08 nM(Ki) 0.14 nM(Ki)
In vitro MK-5172 is a novel P2-P4 quinoxaline macrocyclic NS3/4a protease inhibitor currently in clinical development. The compound demonstrates subnanomolar activity against a broad enzyme panel encompassing major hepatitis C virus (HCV) genotypes as well as variants resistant to earlier protease inhibitors[1].
In vivo In both rat and dog, MK-5172 demonstrates good plasma and liver exposures, with 24-h liver levels suggestive of once-daily dosing. When administered to HCV-infected chimpanzees harboring chronic gt1a or gt1b infections, MK-5172 suppresses viral load between 4 to 5 logs at a dose of 1 mg/kg of body weight twice daily (b.i.d.) for 7 days. MK-5172 demonstrates low to moderate clearance and a modest half-life in both rat and dog. Upon oral administration, MK-5172 demonstrates modest bioavailability of 12 to 13%, with moderate plasma exposure in both species. Significant liver concentrations are achieved in both rat and dog. The 24-h trough liver concentrations are 0.2 μM in rat and 1.4 μM in dog (1 mg per kg), yielding exposure multiples of 27- to 200-fold over the serum-adjusted replicon EC50. MK-5172 proves highly efficacious in vivo at moderate doses against chronic-HCV-infected chimpanzees, including greater viral load suppression than vaniprevir when dosed alternatively to the same animal at an otherwise identical dose and frequency[1].

Protocol (from reference)

Cell Assay:[1]
  • Cell lines

    HB1 cells

  • Concentrations

    2, 5, or 10 nM

  • Incubation Time

    1, 2, 3.5 days

  • Method

    30,000 HB1 cells are seeded per well of a 6-well tissue culture plate per drug concentration. The next day (day 0), the medium is replenished with fresh medium and MK-5172 at the appropriate drug concentration. Cells from a single well per drug concentration are harvested on days 0, 1, and 2, washed, and stored frozen until evaluation. The fourth well is similarly harvested on day 3.5 except that 30,000 cells are reseeded with fresh medium and MK-5172 at the appropriate drug concentration. For additional time points, cells are passaged and harvested every one-half week for 2 weeks. For the third week, cells are similarly treated except that cells received replenishing medium which contained 0.5 mg/ml G418 without protease inhibitor.

Animal Study:[1]
  • Animal Models

    rats or dogs

  • Dosages

    2 mg/kg of body weight (rat) or 0.5 mg/kg (dog)

  • Administration

    i.v.

Selleck's Grazoprevir has been cited by 7 publications

Engineered poly(A)-surrogates for translational regulation and therapeutic biocomputation in mammalian cells [ Cell Res, 2024, 34(1):31-46] PubMed: 38172533
Hepatitis C virus drugs that inhibit SARS-CoV-2 papain-like protease synergize with remdesivir to suppress viral replication in cell culture [ Cell Rep, 2021, 35(7):109133] PubMed: 33984267
HCV Interplay With Mir34a: Implications in Hepatocellular Carcinoma [ Front Oncol, 2021, 11:803278] PubMed: 35127513
Development of a Cell-Based Luciferase Complementation Assay for Identification of SARS-CoV-2 3CLpro Inhibitors [ Viruses, 2021, 13(2)173] PubMed: 33498923
Characterization of fluorescent probe substrates to develop an efficient high-throughput assay for neonatal hepatic CYP3A7 inhibition screening [ Sci Rep, 2021, 11(1):19443] PubMed: 34593846
Hepatitis C Virus Drugs Simeprevir And Grazoprevir Synergize with Remdesivir to Suppress SARS-CoV2 Replication [ BioRxiv, 2020, 10.1101/2020.12.13.422511] PubMed: none
Metabolism of phosphatidylinositol 4-kinase IIIα-dependent PI4P Is subverted by HCV and is targeted by a 4-anilino quinazoline with antiviral activity [ PLoS Pathog, 2012, 8(3):e1002576] PubMed: 22412376

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.