PH-797804 is an ATP-competitive, readily reversible inhibitor of the alpha isoform of human p38 MAP kinase, exhibiting a K(i) = 5.8 nM. PH-797804 blocks inflammation-induced production of cytokines and proinflammatory mediators in human monocyte and synovial fibroblast cell systems, such as prostaglandin E(2), at concentrations that parallel inhibition of cell-associated p38 MAP kinase. PH-797804 effectively inhibits acute inflammatory responses induced by systemically administered endotoxin in both rat and cynomolgus monkeys after oral dosing. PH-797804 exhibited exceptionally high specificity against MAP kinases and the related kinases. No cross-reactivity was observed in large panels of kinase screens (selectivity ratio of >500-fold). In cellular assays, PH-797804 demonstrated superior potency and selectivity consistent with the biochemical measurements. Finally, PH-797804 reduced tumor necrosis factor-alpha and interleukin-6 production in clinical studies after endotoxin administration in a dose-dependent manner, paralleling inhibition of the target enzyme.
| Molecular Weight | 477.3 |
| Formula | C22H19BrF2N2O3 |
| CAS Number | 586379-66-0 |
| Solubility (25°C) | DMSO 90 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
| Related p38 MAPK Products |
|---|
| HWY336
HWY336 is a selective, non-ATP competitive dual MKK4 and MKK7 inhibitor with IC50 values of 6 µM on MKK4 and 10 µM on MKK7 in vitro. HWY336 inhibits the phosphorylation of MKK4/MKK7 inside the activation loop or hinders the substrate to access the kinase. |
| BSJ-04-122
BSJ-04-122 is a covalent MKK4/7 dual inhibitor. BSJ-04-122 inhibits MKK4 and MKK7 with IC50 values of 4 nM and 181 nM, respectively. |
| OVA-E1 peptide TFA
OVA-E1 peptide TFA, is an antagonist variant of SIINFEKL [OVA (257-264). |
| MBP MAPK Substrate
MBP MAPK Substrate is used as an exogenous substrate for MAPK. |
| OVA-E1 peptide
OVA-E1 peptide, is an antagonist variant of SIINFEKL [OVA (257-264). |
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