Lersivirine (UK-453061)

Catalog No.S8055 Batch:S805502

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Technical Data

Formula

C17H18N4O2
Molecular Weight 310.35 CAS No. 473921-12-9
Solubility (25°C)* In vitro DMSO 31 mg/mL (99.88 mM)
Ethanol 16 mg/mL (51.55 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5% DMSO 95% corn oil
1.55mg/ml Taking the 1 mL working solution as an example, add 50 μL of 31 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
1.55mg/ml Taking the 1 mL working solution as an example, add 50 μL of 31 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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 Lersivirine (UK-453061) is a potent and selective inhibitor of nonnucleoside reverse transcriptase (NNRTI) with IC50 of 0.119 μM.
Targets
NNRT [2]

Biological Activity

Description Lersivirine (UK-453061) is a potent and selective inhibitor of nonnucleoside reverse transcriptase (NNRTI) with IC50 of 0.119 μM.
Targets
NNRT [2]
In vitro

Lersivirine binds to HIV-1 wt reverse transcriptase (RT) with Kd of 624 nM. Lersivirine is a very weak inhibitor of human DNA polymerase beta, with an extrapolated geometric mean IC50 of approximately 20 mM resulting in a predicted selectivity index of 166,000. Lersivirine is able to inhibit HIV-1 virus replication in MT-2 cells infected with wt NL4-3, with an EC50 ranging from 5 nM to 35 nM against an MOI ranging from 0.005 to 0.5. Lersivirine retains activity against 80% of viruses with genotypes containing K103N as a single NNRTI mutation (versus 7% for efavirenz), 57% of viruses with genotypes containing Y181C as a single NNRTI mutation (43% for efavirenz), and 46% of viruses with genotypes containing G190A as a single NNRTI mutation (0% for efavirenz). Lersivirine inhibits the replication of strain Ba-L in PBL, with a geometric mean EC50 equal to 3.38 nM (95% CI, 2.26 to 5.05 nM) and an EC90 equal to 9.87 nM (95% CI, 6.63 to 14.7 nM), with no cytotoxicity observed up to 50 μM. Combinations of lersivirine with drugs of the NRTI class (abacavir, didanosine, emtricitabine, lamivudine, tenofovir, and zidovudine) results in synergistic interactions. [1]
In vivo

Lersivirine is not teratogenic in mice.[3]

Protocol (from reference)

Kinase Assay:

[1]
  • RT enzyme assays

    The activities of lersivirine and efavirenz against wt RT (BH10 strain) are determined using a primer extension assay incorporating a DNA/RNA primer/template. The 5’biotinylated primer DNA is a 16mer oligo(dT), which is annealed to a poly(rA) template of approximately 300 bases in length. Incorporation of [3H]TTP(dTTP) by reverse transcription results in extension of the primer. During the reaction the primer/template is bound to a streptavidin-coated flashplate (NEN). The incorporated tritiated nucleotides can then stimulate the scintillant to produce a signal that is measured using a scintillation counter. Compounds that inhibit the RNA-dependent DNA polymerase activity of RT produce a reduced signal.
Cell Assay:

[1]
  • Cell lines

    SupT1 cells

  • Concentrations

    increasing concentrations from 5 nM

  • Incubation Time

    Every 7 days

  • Method

    For inhibitor escalation studies, SupT1 cells are initially infected with HIV-1 NL4-3 wt for 1 h at 37°C and the virus-infected cells are passaged weekly in SupT1 cells in the presence of increasing concentrations of lersivirine from a starting concentration of 5 nM (IC50 in this assay system) in 12-well plates (6 × 105 cells/well). Throughout the passaging period, ongoing virus replication is monitored weekly by observing cytopathic effects (syncytia). Every 7 days, virus supernatant is passaged onto fresh cells at the same density with fresh lersivirine-containing medium. The concentration of lersivirine is increased by 2-fold and 5-fold that of the previous concentration upon subsequent passage whenever evidence of viral replication is observed. Virus stocks for phenotypic characterization are produced in SupT1 cells in the absence of compound and are tested for their sensitivity to lersivirine in an antiviral assay using HeLaP4 cells.
Animal Study:

[3]
  • Animal Models

    Mated Crl:CD1(ICR) mice

  • Dosages

    150 mg/kg, 350 mg/kg, 500 mg/kg

  • Administration

    Oral gavage

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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.