Biological Activity
PF-03715455 is a potent inhaled p38 MAPK inhibitor. PF-03715455 shows some selectivity for p38α over p38β with respective IC50 values of 0.88 and 23 nM. PF-03715455 potently inhibits LPS-induced TNFα production in human whole blood (IC50=1.7 nM). PF-03715455 has potential for the treatment of COPD (chronic obstructive pulmonary disease)[1][2].
In Vitro
PF-03715455 is a moderate inhibitor of CYP1A2, CYP2C19, and CYP2D6 and a potent inhibitor of CYP’s 2C9 and CYP3A4[2].
In Vivo
PF-03715455 treatment shows that the Vss and T1/2 are 0.19 L/kg, 1 hour, respectively[2]. Animal Model: Male CD Sprague Dawley rats (300-450 g)[2] Dosage: 1 mg/kg Administration: I.v. (Pharmacokinetic Analysis) Result: The Vss, and T1/2 were 0.19 L/kg, 1 hour, respectively.
Target
p38α:0.88 nM (IC50)
p38β:23 nM (IC50)
References & source
[1]. Norman P, et al. Investigational p38 inhibitors for the treatment of chronic obstructive pulmonary disease. Expert Opin Investig Drugs. 2015 Mar;24(3):383-92.
[2]. Millan DS, et al. Design and synthesis of inhaled p38 inhibitors for the treatment of chronic obstructive pulmonary disease. J Med Chem. 2011 Nov 24;54(22):7797-814.
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.