1. Metabolic Enzyme/Protease
    Anti-infection
  2. HCV Protease
    HCV

MK-5172 (Synonyms: Grazoprevir)

Cat. No.: HY-15298 Purity: 99.58%
Data Sheet SDS Handling Instructions

MK-5172 is a selective inhibitor of Hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants, with Ki of 0.01 nM (gt1b), 0.01 nM (gt1a), 0.08 nM (gt2a), 0.15 nM (gt2b), 0.90 nM (gt3a), respectively.

For research use only. We do not sell to patients.
MK-5172 Chemical Structure

MK-5172 Chemical Structure

CAS No. : 1350514-68-9

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $118 In-stock
5 mg $90 In-stock
10 mg $140 In-stock
50 mg $450 In-stock
100 mg $650 In-stock
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Other Forms of MK-5172:

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

MK-5172 is a selective inhibitor of Hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants, with Ki of 0.01 nM (gt1b), 0.01 nM (gt1a), 0.08 nM (gt2a), 0.15 nM (gt2b), 0.90 nM (gt3a), respectively.

IC50 & Target

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)[1]

In Vitro

In biochemical assays, MK-5172 is effective against a panel of major genotypes and variants engineered with common resistant mutations, with Ki 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 (gt1bR155K), 0.14±0.03 nM (gt1bD168V), 0.30±0.04 nM (gt1bD168Y), 5.3±0.9 nM (gt1bA156T), and 12±2 nM (gt1bA156V), respectively. In the replicon assay, MK-5172 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 gt1bcon1, gt1a, and gt2a, respectively. MK-5172 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)[1]. 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[2].

In Vivo

MK-5172 demonstrates efficacy in vivo against chronic-HCV-infected chimpanzees[1]. When dosed to dogs, 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 MK-5172 after the 1 mg/kg oral dose is 1.4 μM at the 24 h time point. Similar to its behavior in rats, MK-5172 demonstrates effective partitioning into liver tissue and maintains high liver concentration, relative to potency, 24 h after oral dosing in dogs[2].

Clinical Trial
NCT Number Sponsor Condition Start Date Phase
NCT03144635 Kyushu University|Merck Sharp & Dohme Corp. Hepatitis C Viral|Chronic Kidney Disease stage3 April 1, 2017 Phase 4
NCT02973503 University Hospital, Clermont-Ferrand|Merck Sharp & Dohme Corp.|LC2 PHARMA Chronic HCV Infection November 2016 Phase 3
NCT02105662 Merck Sharp & Dohme Corp. Chronic Hepatitis C June 2014 Phase 3
NCT03098121 Taoyuan General Hospital|Merck Sharp & Dohme Corp. To Assess the Efficacy of Grazoprevir 100mg and Elbasvir 50mg by Determining the Proportion of Sustained Virological Response 12 Weeks After the End of Therapy June 20, 2017 Phase 4
NCT02940691 Kirby Institute Hepatitis C December 2016 Phase 4
NCT01537900 Merck Sharp & Dohme Corp. Hepatitis C October 2013 Phase 1
NCT03222167 Institute Of Cardiology & Internal Diseases, Kazakhstan|Schering-Plough|Synergy Research Group Chronic Hepatitis C Genotype 1B|Metabolic Syndrome|Fibrosis, Liver|Cirrhoses, Liver October 2017 Phase 3
NCT01667081 Merck Sharp & Dohme Corp. Hepatitis C October 17, 2012
NCT02600325 Erasmus Medical Center Acute Hepatitis C|Human Immunodeficiency Virus|Hepatitis C February 2016 Phase 3
NCT02105688 Merck Sharp & Dohme Corp. Chronic Hepatitis C September 2, 2014 Phase 3
NCT01440595 Merck Sharp & Dohme Corp. Hepatitis C, Chronic November 2011 Phase 2
NCT03145623 University Hospital, Toulouse|MSD France Hepatitis C|Chronic Kidney Diseases June 2, 2017
NCT00998985 Merck Sharp & Dohme Corp. Hepatitis C February 2010 Phase 1
NCT02105701 Merck Sharp & Dohme Corp. Hepatitis C Infection June 2014 Phase 3
NCT02251990 Merck Sharp & Dohme Corp. Hepatitis C January 28, 2015 Phase 3
NCT02945150 Massachusetts General Hospital|Merck Sharp & Dohme Corp. Renal Failure February 1, 2017 Phase 4
NCT01716156 Merck Sharp & Dohme Corp. Hepatitis C January 2013 Phase 2
NCT02133131 Merck Sharp & Dohme Corp. Hepatitis C June 2014 Phase 2
NCT02902120 University of Maryland Hepatitis C|Renal Insufficiency, Chronic|Disorder of Transplanted Kidney May 1, 2017 Phase 4
NCT01710501 Merck Sharp & Dohme Corp. Chronic Hepatitis C (CHC) December 2012 Phase 2
NCT03022006 Norte Study Group|Merck Sharp & Dohme Corp. Chronic Hepatitis C January 15, 2017 Phase 4
NCT01390428 Merck Sharp & Dohme Corp. Hepatitis C July 2011 Phase 1
NCT02886624 Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba|Merck Sharp & Dohme Corp.|Institut National de la Santé Et de la Recherche Médicale, France Acute Hepatitis C|HIV May 24, 2017 Phase 2
NCT02252016 Merck Sharp & Dohme Corp. Hepatitis C October 22, 2014 Phase 3
NCT02647632 French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS) Hepatitis C January 2016 Phase 2
NCT03111966 Hepa C Hepatitis C March 31, 2017
NCT02092350 Merck Sharp & Dohme Corp. Hepatitis C Virus March 2014 Phase 2|Phase 3
NCT03026023 Raymond T. Chung, MD|Merck Sharp & Dohme Corp.|Massachusetts General Hospital Cardiac Transplant Disorder|Hepatitis C December 1, 2017 Phase 4
NCT01547312 Merck Sharp & Dohme Corp. Chronic Hepatitis C May 2012 Phase 1
NCT01937975 Merck Sharp & Dohme Corp. Chronic Hepatitis C|Renal Impairment September 2013 Phase 1
NCT01932762 Merck Sharp & Dohme Corp. Hepatitis C October 2013 Phase 2
NCT02115321 Merck Sharp & Dohme Corp. Chronic Hepatitis C May 2014 Phase 2|Phase 3
NCT02204475 Merck Sharp & Dohme Corp. Hepatitis C November 2014 Phase 3
NCT02358044 Merck Sharp & Dohme Corp. Hepatitis C February 27, 2015 Phase 3
NCT02105467 Merck Sharp & Dohme Corp. Chronic Hepatitis C Virus June 2014 Phase 3
NCT02601573 Merck Sharp & Dohme Corp. Hepatitis C January 2016 Phase 2
NCT02203149 Merck Sharp & Dohme Corp. Hepatitis C August 2014 Phase 2|Phase 3
NCT03110055 Tel-Aviv Sourasky Medical Center|Merck Sharp & Dohme Corp. HCV, HCC May 1, 2017
NCT01717326 Merck Sharp & Dohme Corp. Hepatitis C February 2013 Phase 2
NCT02105454 Merck Sharp & Dohme Corp. Hepatitis C Virus May 2014 Phase 2
NCT02332707 Merck Sharp & Dohme Corp. Hepatitis C January 22, 2015 Phase 2
NCT02332720 Merck Sharp & Dohme Corp. Hepatitis C January 28, 2015 Phase 2
NCT03105349 Fundacion SEIMC-GESIDA HCV July 15, 2017 Phase 4
NCT01353911 Merck Sharp & Dohme Corp. Hepatitis C, Chronic June 2011 Phase 2
NCT02785666 University of Zurich Hepatitis C|HIV June 2016 Phase 3
NCT02897596 Fundacion Clinic per a la Recerca Biomédica Hepatitis C|HIV September 2016 Phase 3
NCT02890719 Fundacion Clinic per a la Recerca Biomédica Liver Transplantation|Hepatitis C September 2016 Phase 3
NCT03093415 Oregon Health and Science University Hepatitis C|Substance Use Disorders|Substance Abuse, Intravenous May 30, 2017 Phase 4
NCT02786537 University of Florida|Patient-Centered Outcomes Research Institute|Merck Sharp & Dohme Corp.|AbbVie Chronic Hepatitis C June 2016 Phase 4
NCT02333292 Valme University Hospital|Hospital del SAS de Jerez|Hospital General Universitario Elche|Hospital La Línea de la Concepción|Complexo Hospitalario Universitario de A Coruña|Hospital de Figueres|Hospital Universitario Puerto Real|Hospital Universitario Virgen de la Victoria|Hospital Universitario de Canarias|Hospital General Universitario de Alicante|Hospital Universitario Araba|Hospital Royo Vilanova|Hospital Universitario de Burgos|Complejo Hospitalario Universitario de Huelva|Hospital Universitario Reina Sofia|Hospital Universitario Virgen Macarena|Complexo Hospitalario Universitario de Vigo|Clinica Universidad de Navarra, Universidad de Navarra|Hospital Clinico Universitario San Cecilio|Hospital Universitario La Fe|Hospital General Universitario de Valencia|Hospital Universitario Infanta Leonor|Hospital Universitario de Gran Canaria|Hospital General Universitario Santa Lucía|Centro Penitenciario Alicante 1|Hospital Regional Universitario Carlos Haya|Hospital Virgen de la Luz|Hospital General Universitario de Castellón|Hospital Parc Taulí, Sabadell Chronic Hepatitis C Infection December 2014
NCT03143998 Merck Sharp & Dohme Corp. Hepatitis C November 29, 2017 Phase 4
NCT03111108 Merck Sharp & Dohme Corp. Hepatitis C Virus (HCV) Infection June 20, 2017 Phase 4
NCT02732405 Istituto Clinico Humanitas|CD Pharma Group S.r.l. Hepatitis C|Compensated Cirrhosis May 2016 Phase 3
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References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 1.3040 mL 6.5198 mL 13.0395 mL
5 mM 0.2608 mL 1.3040 mL 2.6079 mL
10 mM 0.1304 mL 0.6520 mL 1.3040 mL
Kinase Assay
[1]

Recombinant HCV NS3/4A enzymes are expressed and purified from Escherichia colias. Enzyme sequences are derived from genotype 1a (gt1a) H77, gt1b con1, gt2a JFH1, gt2b HCJ8, and gt3a NZL1. Inhibition of HCV NS3/4A protease activity in reaction mixtures containing MK-5172, Vaniprevir, or the reference compounds Danoprevir and TMC435 is determined in a time-resolved fluorescence assay. Cell-based HCV replicon assays are conducted in genotype 1b (con1) stable cell line HB1 or a gt2a cell line (JFH) in the presence of either 10% fetal bovine serum (FBS) or 40% normal human serum (NHS). Determinations of 50% effective concentrations (EC50s) against the panel of genotype or mutant replicon cell lines are conducted using a TaqMan-based assay. The 50% cytotoxic concentration (CC50) is determined in the HCV replicon cell line with the use of an MTS assay. Potency determinations against clinical genotype 1 NS3/4A sequences are made using a transient cell-based phenotype assay. The NS3/4A patient isolates are cloned from human plasma infected with HCV. Broad counterscreening, in which MK-5172 is evaluated for its inhibitory potency at a concentration of 10 μM, is conducted at MDS Pharma Services[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

MK-5172 is formulated in polyethylene glycol 200 (PEG200)[1].

Rat and Dog[1]
Studies are performed in both rats and dogs. For studies in which MK-5172 is dosed intravenously to rats or dogs, the compound is formulated in polyethylene glycol 200 (PEG200) and administered as a bolus at either 2 mg/kg of body weight (rat) or 0.5 mg/kg (dog). For oral studies, the crystalline potassium salt of the compound is dosed as a solution in PEG400 at 5 mg/kg (rat) or 1 mg/kg (dog). For all studies, blood samples are collected in EDTA-containing tubes at appropriate times and plasma is separated by centrifugation and stored at −70°C until analysis. Quantitation of MK-5172 levels is conducted by high-performance liquid chromatography/mass spectroscopy (LC/MS/MS) following protein precipitation. Liver samples are obtained from rat studies at the termination of the experiment. For dog, liver biopsy samples (20 μL) are collected following sedation. Tissue samples are homogenized in four volumes of deionized water, and drug concentrations are determined by LC/MS/MS after protein precipitation. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

766.9

Formula

C₃₈H₅₀N₆O₉S

CAS No.

1350514-68-9

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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MK-5172
Cat. No.:
HY-15298
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