Doravirine

Catalog No.S6492 Batch:S649201

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Technical Data

Formula

 C17H11C1F3N5O3

 
Molecular Weight 425.75 CAS No. 1338225-97-0
Solubility (25°C)* In vitro DMSO 85 mg/mL (199.64 mM)
Water Insoluble
Ethanol 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.)

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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.
Targets
K103N HIV-1 RT [1] Y181C HIV-1 RT [1] WT HIV-1 RT [1]
9.7 nM 9.7 nM 12 nM
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 Study:

[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

Selleck's Doravirine has been cited by 1 publication

Chemical inhibition of DPP9 sensitizes the CARD8 inflammasome in HIV-1-infected cells [ Nat Chem Biol, 2023, 19(4):431-439] PubMed: 36357533

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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.