[CAS NO. 1240516-71-5] GSK2239633A
PRODUCTS SPECIFICATIONS [1240516-71-5]
DESCRIPTION [1240516-71-5]
Overview
| MDL | MFCD30533311 |
|---|---|
| Molecular Weight | 549.06 |
| Molecular Formula | C24H25ClN4O5S2 |
| SMILES | CC(C)(O)C(NCC1=CC=CC(CN2N=C(NS(=O)(C3=CC=C(Cl)S3)=O)C4=C2C=CC=C4OC)=C1)=O |
Summary
IC50 & Target
|
[ 125 I]-TARC-CCR4 7.96 (pIC 50 ) |
In Vitro
The GSK2239633A is an allosteric antagonist of human CCR4. GSK2239633A inhibits the binding of [ 125 I]-TARC to human CCR4 with a pIC 50 of 7.96±0.11 and also inhibits thymus- and activation-regulated chemokine-induced (TARC)-induced increases in the F-actin content of isolated human CD4 + CCR4 + T-cells with a pA 2 of 7.11±0.29 [1] . The effect of GSK2239633A (Compound 3) on CCL17-induced increases in the F-actin content of human CD4 + CCR4 + T cells is measured. The pEC 50 value is 8.79±0.22 [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Following intravenous dosing, plasma GSK2239633A displays rapid, bi-phasic distribution and slow terminal elimination (t 1/2 : 13.5 hours), suggesting that GSK2239633A is a low to moderate clearance drug. Following oral dosing, blood levels of GSK2239633A reach C max rapidly (median t max : 1.0-1.5 hours). Estimated GSK2239633A bioavailability is low with a maximum value determined of only 16% [1] . GSK2239633A (Compound 9) demonstrates good pharmacokinetic data in preclinical animal studies (bioavailability in rats and beagle dogs 85% and 97% respectively) [3] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 250 mg/mL ( 455.32 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.8213 mL | 9.1065 mL | 18.2129 mL |
| 5 mM | 0.3643 mL | 1.8213 mL | 3.6426 mL |
| 10 mM | 0.1821 mL | 0.9106 mL | 1.8213 mL |
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1.
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2.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.08 mg/mL (3.79 mM); Clear solution
References
- [1] Cahn A, et al. Safety, tolerability, pharmacokinetics and pharmacodynamics of GSK2239633, a CC-chemokine receptor 4 antagonist, in healthy male subjects: results from an open-label and from a randomised study. BMC Pharmacol Toxicol. 2013 Feb 28;14:14.
- [2] Slack RJ, et al. Antagonism of human CC-chemokine receptor 4 can be achieved through three distinct binding sites on the receptor. Pharmacol Res Perspect. 2013 Dec;1(2):e00019.
- [3] Miah AH, et al. Identification of pyrazolopyrimidine arylsulfonamides as CC-chemokine receptor 4 (CCR4) antagonists. Bioorg Med Chem. 2017 Oct 15;25(20):5327-5340.
