Doravirine (MK-1439)

Catalog No.S6492

For research use only.

Doravirine is a novel HIV-1 nonnucleoside reverse transcriptase inhibitor with IC50 values of 12, 9.7, and 9.7 nM against the wild type (WT) and K103N and Y181C reverse transcriptase (RT) mutants, respectively, in a biochemical assay. It is highly specific with minimum off-target activities.

Doravirine (MK-1439) Chemical Structure

CAS No. 1338225-97-0

Purity & Quality Control

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Biological Activity

Description Doravirine is a novel HIV-1 nonnucleoside reverse transcriptase inhibitor with IC50 values of 12, 9.7, and 9.7 nM against the wild type (WT) and K103N and Y181C reverse transcriptase (RT) mutants, respectively, in a biochemical assay. It is highly specific with minimum off-target activities.
In vitro

MK-1439 exhibits greater than 10,000-fold selectivity with respect to the cellular DNA polymerases α, ß, and γ with IC50s of >100 μM. In the screen with more than 110 protein targets including enzymes, transporters, ion channels, and receptor, MK-1439 shows an IC50 of greater than 10 μM against all targets except 5-HT2ß, where an IC50 of 2.5 μM is noted in a ligand binding assay. However, the 5-HT2ß activity is not observed in a functional cell-based assay monitoring the accumulation of inositol-1-phosphate. Therefore, the binding activity does not appear to translate into a 5-HT2ß functional response. MK-1439 does not display cytotoxicity in activated CD4+ T cells, PBMCs, monocytes, macrophages proliferating transformed cell lines, such as MT4, SupT1, and HL60 cell lines at concentrations of up to 100 μM[1].

In vivo

In rats dosed IV at 1 mpk (60%PEG200), the clearance (CL) of MK-1439 is 5.4 mL/min/kg and the half time is 4.4 hr. Its volume of distribution (Vd) is 2.3 L/kg. The oral bioavailability of MK-1439 is 57% (doesed PO at 5 mpk). In dogs dosed IV at 0.5 mpk, the CL of MK-1439 is 0.36 mL/min/kg and half-time is 37 hr. The oral bioavailability of MK-1439 is 52% (doesed PO at 1 mpk). Overall, The pharmacokinetic profile of MK-1439 in preclinical species is favorable[2].

Protocol (from reference)

Animal Research:

[2]

  • Animal Models: 60% PEG200 (IV); Ball-milled, 0.5% methocel (PO in rats); Ball-milled, 10% Tween (PO in dogs)
  • Dosages: 1 mpk (IV in rats); 5 mpk (PO in rats); 0.5 mpk (IV in dogs); 1 mpk (PO in dogs)
  • Administration: IV or PO

Solubility (25°C)

In vitro

DMSO 85 mg/mL
(199.64 mM)
Water Insoluble
Ethanol Insoluble

Chemical Information

Molecular Weight 425.75
Formula

 C17H11C1F3N5O3

 
CAS No. 1338225-97-0
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CN1C(=NNC1=O)CN2C=CC(=C(C2=O)OC3=CC(=CC(=C3)C#N)Cl)C(F)(F)F

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04894357 Not yet recruiting Other: Phenotypic resistance measure HIV-1-infection Fundación Pública Andaluza para la Investigación Biomédica Andalucía Oriental September 1 2021 --
NCT04900974 Recruiting Drug: Doravirine HIV Infections|Pregnancy Related University of North Carolina Chapel Hill|Merck Sharp & Dohme Corp. June 29 2021 Phase 1
NCT04689737 Completed Drug: Doravirine HIV-infected Participants With ESRD Undergoing Routine Hemodialysis Fundación FLS de Lucha Contra el Sida las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia|Merck Sharp & Dohme Corp. March 20 2021 Phase 4
NCT04513626 Recruiting Drug: DORAVIRINE 100 MG [Pifeltro] HIV Infections Centre de Recherches et d''Etude sur la Pathologie Tropicale et le Sida September 15 2020 Phase 2
NCT04079452 Not yet recruiting Drug: Doravirine|Drug: Descovy HIV-1-infection Fundación FLS de Lucha Contra el Sida las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia|Institut d''Investigació Biomèdica de Bellvitge|Hospital Universitari de Bellvitge June 2020 Phase 3

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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