| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
Elbasvir (formerly known as MK-8742; MK8742; trade name Zepatier) is a potent NS5A (nonstructural protein 5A) inhibitor with anti-HCV (hepatitis C virus) activities against different HCV genotypes.It was being developed to be a part of combination treatment regimens for chronic HCV infection that included the NS3/4A protease inhibitor grazoprevir (either with or without ribavirin). 48 noncirrhotic adult men with chronic genotype 1 or 3 infections were randomized to receive either a placebo or elbasvir at doses of 5 to 50 mg (genotype 1) or 10 to 100 mg (genotype 3) once daily for five days. The purpose of the phase 1b dose-escalating study was to evaluate the virologic responses of the men. In vitro, resistance-associated variants (RAVs) were suppressed in a dose-dependent manner by elbasvir. The majority of the time, loci 30, 31, and 93 were involved in the selection of variants that conferred high-level elbasvir resistance. These variants were selected by encoding multiple amino acid substitutions. Patients with genotype 1b showed higher reductions in HCV RNA levels in the monotherapy study compared to patients with genotype 1a at all elbasvir doses; generally, responses in patients with genotype 3 were less marked than in those with genotype 1, especially at lower elbasvir doses. Elbasvir monotherapy selected the predominant RAVs that were identified as M28T, Q30R, L31V, and Y93H in genotype 1a, L31V and Y93H in genotype 1b, and A30K, L31F, and Y93H in genotype 3. Preclinical observations and patient virologic results were in agreement. The amino acid positions 28, 30, 31, and 93 are where NS5A-RAVs most frequently appeared in the laboratory and clinical trial. (The MK-8742 P002 trial has been registered at ClinicalTrials.gov under identifier NCT01532973.).
| Targets |
HCV 1a (EC50 = 4 nM); HCV 1b (EC50 = 3 nM); HCV 2a (EC50 = 3 nM)
|
||
|---|---|---|---|
| ln Vitro |
Elbasvir exhibits strong activity against the 1a and 1b genotype replicons, as evidenced by its EC90 of 0.006 nM for the 1a_H77 wild-type and 1b_con1 replicons. With an EC90 of 0.12 nM, elasvir inhibits genotype 3 replicons. The decreases in colony counts at higher doses of elbasvir (0.06 nM, 0.6 nM, and 6 nM) show dose-dependent suppression of resistant genotype 1a replicons. With EC50s in the low-picomolar range, elbasvir exhibits high potency against HCV replicons carrying NS5A sequences from GT1a, -1b, -2a(31L), -3a, -4a, -5a, and -6.
|
||
| ln Vivo |
|
||
| Enzyme Assay |
Elbasvir is an HCV NS5A inhibitor that, depending on genotype, has a median EC50 value ranging from 0.2 to 3600 pmol/L. It inhibits the replication of the hepatitis C virus and the assembly of virion.
|
||
| Cell Assay |
Elbasvir (formerly known as MK-8742; MK8742; trade name Zepatier) is a potent inhibitor of nonstructural protein 5A (NS5A) that exhibits anti-hepatitis C virus (HCV) properties against various HCV genotypes.
|
||
| Animal Protocol |
|
||
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Elbasvir reaches peak plasma concentration 3-6 hours after administration and has an absolute bioavailability of 32%. When co-administered with food, the peak concentration of elbasvir increases 1.5-fold, but this increase in exposure is not likely to be clinically relevant. Elbasvir is mainly eliminated in the feces (90%) with very little eliminated in the urine (<1%). Elbasvir has an estimated apparent volume of distribution of 680 liters. It is thought to distribute into most tissues including the liver. The clearance of elbasvir has not been determined. Metabolism / Metabolites Elbasvir is partially eliminated by oxidative metabolism meditated by CYP3A. No circulating metabolites of elbasvir have been detected in human plasma. Biological Half-Life The geometric mean apparent terminal half-life for elbasvir is 24 hours in HCV-infected subjects. |
||
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation Elbasvir has not been studied in nursing mothers being treated for hepatitis C infection. Because it is greater than 99.9% bound to maternal plasma proteins, amounts in breastmilk are likely to be very low. Some sources recommend against breastfeeding when elbasvir is used with ribavirin. Hepatitis C is not transmitted through breastmilk and breastmilk has been shown to inactivate hepatitis C virus (HCV). However, the Centers for Disease Control recommends that mothers with HCV infection should consider abstaining from breastfeeding if their nipples are cracked or bleeding. It is not clear if this warning would apply to mothers who are being treated for hepatitis C. Infants born to mothers with HCV infection should be tested for HCV infection; because maternal antibody is present for the first 18 months of life and before the infant mounts an immunologic response, nucleic acid testing is recommended. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding Elbasvir is more than 99.9% bound to plasma proteins. It binds both human serum albumin and α1-acid glycoprotein. |
||
| References |
|
||
| Additional Infomation |
Pharmacodynamics
Elbasvir is classified as a direct-acting antiviral (DAA) and prevents viral replication in HCV genotypes 1a, 1b, and 4. |
| Molecular Formula |
C49H55N9O7
|
|
|---|---|---|
| Molecular Weight |
882.02
|
|
| Exact Mass |
881.422
|
|
| Elemental Analysis |
C, 66.72; H, 6.29; N, 14.29; O, 12.70
|
|
| CAS # |
1370468-36-2
|
|
| Related CAS # |
|
|
| PubChem CID |
71661251
|
|
| Appearance |
White to yellow solid powder
|
|
| Density |
1.4±0.1 g/cm3
|
|
| Index of Refraction |
1.701
|
|
| LogP |
6.98
|
|
| Hydrogen Bond Donor Count |
4
|
|
| Hydrogen Bond Acceptor Count |
9
|
|
| Rotatable Bond Count |
13
|
|
| Heavy Atom Count |
65
|
|
| Complexity |
1680
|
|
| Defined Atom Stereocenter Count |
5
|
|
| SMILES |
O=C([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C(=O)OC([H])([H])[H])N1C([H])([H])C([H])([H])C([H])([H])C1([H])C1=NC([H])=C(C2C([H])=C([H])C3=C(C=2[H])C([H])=C2C4C([H])=C([H])C(=C([H])C=4O[C@@]([H])(C4C([H])=C([H])C([H])=C([H])C=4[H])N23)C2=C([H])N=C([C@]3([H])C([H])([H])C([H])([H])C([H])([H])N3C([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C(=O)OC([H])([H])[H])=O)N2[H])N1[H]
|
|
| InChi Key |
BVAZQCUMNICBAQ-PZHYSIFUSA-N
|
|
| InChi Code |
InChI=1S/C49H55N9O7/c1-27(2)41(54-48(61)63-5)45(59)56-20-10-14-37(56)43-50-25-34(52-43)30-17-19-36-32(22-30)23-39-33-18-16-31(24-40(33)65-47(58(36)39)29-12-8-7-9-13-29)35-26-51-44(53-35)38-15-11-21-57(38)46(60)42(28(3)4)55-49(62)64-6/h7-9,12-13,16-19,22-28,37-38,41-42,47H,10-11,14-15,20-21H2,1-6H3,(H,50,52)(H,51,53)(H,54,61)(H,55,62)/t37-,38-,41-,42-,47-/m0/s1
|
|
| Chemical Name |
methyl N-[(2S)-1-[(2S)-2-[5-[(6S)-3-[2-[(2S)-1-[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]pyrrolidin-2-yl]-1H-imidazol-5-yl]-6-phenyl-6H-indolo[1,2-c][1,3]benzoxazin-10-yl]-1H-imidazol-2-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate
|
|
| Synonyms |
Elbasvir; Zepatier; MK8742; MK 8742; MK-8742
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1338 mL | 5.6688 mL | 11.3376 mL | |
| 5 mM | 0.2268 mL | 1.1338 mL | 2.2675 mL | |
| 10 mM | 0.1134 mL | 0.5669 mL | 1.1338 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04048850 | Active Recruiting |
Drug: Elbasvir/Grazoprevir 50 MG-100 MG Oral Tablet [ZEPATIER] |
Hepatitis C Hiv |
University of Illinois at Chicago |
September 20, 2019 | |
| NCT02251990 | Completed | Drug: Grazoprevir/Elbasvir Drug: Placebo |
Hepatitis C | Merck Sharp & Dohme LLC | January 28, 2015 | Phase 3 |
| NCT01797536 | Completed | Drug: Elbasvir | Hepatic Insufficiency | Merck Sharp & Dohme LLC | Merck Sharp & Dohme LLC | Phase 1 |
Kinetics of HCV RNA reduction in GT1a(H77) replicons bearing NS3 and NS5A RAVs treated with elbasvir and grazoprevir. (A) Inhibition of GT1a_R155K (□, ■) and wild-type GT1a (○, ●) with DMSO (open symbols) and 6 pM elbasvir (closed symbols) over 14 days. (B) Inhibition of Q30D (□, ■), Y93H (▽, ▼), and wild-type GT1a (○, ●) with DMSO (open symbols) and 15 nM grazoprevir (closed symbols) over 14 days.Antimicrob Agents Chemother.2016 Apr 22;60(5):2954-64. |
|---|
The combination of grazoprevir and elbasvir additively inhibits HCV RNA replication in GT1a(H77) replicon cells.Synergy plots of three independent runs (performed in triplicate) were analyzed by MacSynergy. Antimicrob Agents Chemother.2016 Apr 22;60(5):2954-64. |
Representative images of a colony formation assay for the combination of grazoprevir and elbasvir in GT1a(H77) replicon cells. Multiples of the EC90values of both inhibitors were titrated in a matrix and scored for the emergence of resistant colonies. Higher concentrations of the combination were evaluated in panel A than in panel B to finely map the combinatorial effect. Antimicrob Agents Chemother.2016 Apr 22;60(5):2954-64. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
