product name TAK-715
Description: TAK-715 is a potent p38 MAPK inhibitor for p38α with IC50 of 7.1 nM, which is 28-fold more selective for p38α over p38β, it shows no inhibition to p38γ/δ, JNK1, ERK1, IKKβ, MEKK1 or TAK1. TAK-715 displays potent inhibitory activity (inhibition of p38alpha, IC50 = 7.1 nM; LPS-stimulated release of TNF-alpha from THP-1, IC50 = 48 nM. TAK-715 was selected as a clinical candidate and is now under clinical investigation for the treatment of RA.
References: J Med Chem. 2005 Sep 22;48(19):5966-79; Chem Biol. 2011 Apr 22;18(4):485-94.
399.51
Formula
C24H21N3OS
CAS No.
303162-79-0
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 80 mg/mL (200.2 mM)
Water: <1 mg/mL
Ethanol: 16 mg/mL (40.0 mM)
Solubility (In vivo)
30% propylene glycol, 5% Tween 80, 65% D5W: 30 mg/mL
Synonyms
other peoduct :
| In Vitro |
In vitro activity: TAK 715 inhibits LPS-stimulated release of TNF-alpha from THP-1 with IC50 of 48 nM. TAK 715 (10 μM) inhibits Wnt-3a-induced hDvl2 phosphorylation and the hDvl2 shift in U2OS-EFC cells. The amide NH of TAK 715 is hydrogen bonded to the main-chain carbonyl of Met109 of p38 alpha. TAK 715 binds relatively high in the ATP pocket, occupying the hydrophobic back pocket, the adenine region and the front pocket of p38 as well as extending to most of the length of the Gly-rich loop. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | TAK 715 (10 mg/kg, po) inhibits LPS-induced TNF-alpha production in mice with 87.6% inhibition. TAK 715 has a modest mouse bioavailability of 18.4% and a slightly improved rat bioavailability of 21.1%. TAK 715 has a modest mouse bioavailability of 18.4% and a slightly improved rat bioavailability of 21.1%. TAK 715 results in Cmax of 0.19 μg/mL and AUC(0-24 hours) of 1.16 μg·h/mL in rats. TAK 715 (30 mg/kg, po) significantly reduces the secondary paw volume with 25 % inhibition in a rat adjuvant-induced arthritis (AA) model. |
| Animal model | Adjuvant-induced arthritis (AA) rat model |
| Formulation & Dosage | Dissolved in saline; 30 mg/kg; p.o. |
| References | J Med Chem. 2005 Sep 22;48(19):5966-79; Chem Biol. 2011 Apr 22;18(4):485-94. |
