GSK3739936
GSK3739936 (BMS-986180) is a potent HIV-1 allosteric integrase inhibitor with an IC50 value of 11.1 nM and an EC50 value of 1.7 nM. GSK3739936 is also a weak CYP inhibitor (IC50>24.3 μM). GSK3739936 shows favorable pharmacokinetic property in preclinical species with rapid absorption, low to moderate clearance and excellent oral bioavailability.
For research use only. We do not sell to patients.
- CAS No.: 1803444-21-4
- Formula: C34H43FN2O4
- Molecular Weight:562.71
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
IC50: 11.1 nM (HIV-1 integrase)[1]
EC50: 1.7 nM (HIV-1 integrase)[1]
IC50: >24.3 μM (CYP)[1]
Cellular Effect
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Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| MT2 | CC50 |
≥33.5 μM
Compound: 29
|
Cytotoxicity against human MT2 cells assessed as cell viability measured after 4 days by XTT assay
Cytotoxicity against human MT2 cells assessed as cell viability measured after 4 days by XTT assay
|
[PMID: 35235334] |
| MT2 | CC50 |
>=18.2 μM
Compound: 1
|
Cytotoxicity against human MT2 cells infected with HIV1 NLRep-Rluc harbouring polymorphic 124T/125T integrase
Cytotoxicity against human MT2 cells infected with HIV1 NLRep-Rluc harbouring polymorphic 124T/125T integrase
|
[PMID: 35605346] |
| MT2 | CC50 |
>=22 μM
Compound: 4; GSK37399363
|
Cytotoxicity against human MT2 cells
Cytotoxicity against human MT2 cells
|
[PMID: 35707159] |
In Vitro
GSK3739936 is not cytotoxic to MT-2 cells, exhibiting CC50 values of >20 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
Pharmacokinetic Parameters of GSK3739936 in Preclinical Species[1].
| Male CD-1 mice | Male Sprague-Dawley rats | Cynomolgus monkey | Male beagle dogs | |
| IV dose (mg/kg) | 1 | 1 | 1 | 1 |
| CL (mL/min/kg) | 5.4 | 5.5 | 14.5 | 2.9 |
| t1/2 (h) | 6.3 | 4.3 | 2.4 | 5.1 |
| Vss (L/kg) | 2.4 | 1.8 | 1.5 | 0.7 |
| PO dose (mg/kg) | 5 | 5 | 2 | 2 |
| Cmax (nM) | 2361 | 2762 | 525 | 2963 |
| tmax (h) | 5 | 2.7 | 2 | 2 |
| AUC (nM·h) | 24516 | 14022 | 2231 | 18471 |
| F (%) | 89 | 52 | 54 | 75 |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male CD-1 mice, male Sprague-Dawley rats, cynomolgus monkey and male beagle dogs[1]
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Dosage:1 mg/kg for IV; 5 or 2 mg/kg for PO
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Administration:PO or IV; single dosage
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Result:Exhibited a low clearance in the mouse, rat, and dog with moderate to long elimination half-lives, while displays moderate clearance and a short elimination half-life in the cynomolgus monkey.
The absolute oral bioavailability ranged between 52 and 89%.
The tmax value of 2-5 h suggesting rapid absorption in all four species.
Chemical Information
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CAS No. 1803444-21-4
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Molecular Weight 562.71
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Formula C34H43FN2O4
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SMILES
CC1=NC(C)=C(C(N2CCC(C)(CC2)C)=C1[C@@H](C(O)=O)OC(C)(C)C)C3=CC=C(C=C3)OCCC4=CC=C(C=C4)F
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Synonyms
BMS-986180
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Protocol for Pharmacokinetic Study
Pharmacokinetic studies quantify how an organism handles a drug over time through absorption, distribution, metabolism, and excretion, and the core experimental readout is the concentration-time profile of parent drug and, when relevant, metabolites in biological matrices such as plasma, whole blood, urine, bile, or tissue. Pharmacokinetic analysis links dose, route, exposure, clearance, half-life, distribution, bioavailability, and systemic exposure to drug efficacy and toxicity hypotheses rather than measuring a signaling pathway directly. The literature links pharmacokinetics to drug-development phenotypes by showing that drug metabolism and pharmacokinetics influence compound progression, exposure-response interpretation, safety margins, dosing strategy, and failure risk during discovery and development. DMPK science contributes to compound optimization by integrating physicochemical properties, in vitro metabolism, transporter behavior, in vivo exposure, and pharmacodynamic contex
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)