Pamapimod is a novel p38 mitogen-activated protein kinase inhibitor, inhibited p38alpha and p38beta enzymatic activity, with IC50 values of 0.014 +/- 0.002 and 0.48 +/- 0.04 microM, respectively. Pamapimod also inhibited lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) α production by monocytes, interleukin (IL)-1β production in human whole blood, and spontaneous TNFα production by synovial explants from RA patients. LPS- and TNFα-stimulated production of TNFα and IL-6 in rodents also was inhibited by pamapimod.
In vivo: In murine collagen-induced arthritis, pamapimod reduced clinical signs of inflammation and bone loss at 50 mg/kg or greater. In a rat model of hyperalgesia, pamapimod increased tolerance to pressure in a dose-dependent manner, suggesting an important role of p38 in pain associated with inflammation.
|Cell lines||Human Monocytic Cell Line, THP-1|
|Preparation method||THP-1 cells, growing in log phase, were collected by centrifugation and resuspended in RPMI 1640 containing 5.5×10-5 M 2-mercaptoethanol and 10% fetal bovine serum to a final cell concentration of 2.5×106 cells/ml. Dilutions of pamapimod were predispensed in 25 μl aliquots (before addition of cells) into round-bottom 96-well plates. The starting concentration was 100 μM in 5% dimethyl sulfoxide, and six half-log serial dilutions were made. After the addition of 200 μl of cell suspension and 25 μl of 5 μg/ml LPS in medium, the final dimethyl sulfoxide concentration was 0.5%. Compounds were diluted an additional 10-fold, and the final LPS concentration was 500 ng/ml. The cell suspensions and compound dilutions were combined and incubated for 30 min at 37°C in a 5% CO2 humidified atmosphere, before the addition of LPS (or medium for non-LPS control samples). After the addition of LPS, plates were incubated for 2 h, followed by centrifugation to pellet cells. Cell supernatants were stored at 4°C until analysis for TNF-α content. TNF-α levels were determined by ELISA. Cytokine concentrations were determined.|
|Incubation time||150 min|
|Animal models||BALB/c mice|
|Formulation||0.9% NaCl, 0.5% sodium carboxymethylcellulose, 0.4% polysorbate 80, 0.9% benzyl alcohol, and 97.3% distilled water.|
|Dosages||25, 50, 100, 150 mg/kg|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 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 resveratrol of 11.2 mg/kg.
|Solubility||DMSO 80 mg/mL
Ethanol 20 mg/mL
Pamapimod, a novel p38 mitogen-activated protein kinase inhibitor: preclinical analysis of efficacy and selectivity.
Hill RJ, et al. J Pharmacol Exp Ther. 2008 Dec;327(3):610-9. PMID: 18776065.
|Related p38 MAPK Products|
BMS-582949 is a potent and selective P38 mitogen-activated protein kinase (P38 MAPK) inhibitor with IC50 of 13nM.
R1487 Hydrochloride is an orally bioavailable and highly selective inhibitors of p38α mitogen-activated protein kinase.
Dilmapimod (also known as SB-681323 and GW-681323) is a p38 MAPK inhibitor that potentially suppresses inflammation in COPD.
SB 239063 is a potent and selective p38 MAPK inhibitor (IC50 = 44 nM for p38α). SB 239063 displays > 220-fold selectivity over ERK, JNK1 and other kinases; ~ 3-fold more selective than SB 203580.
SD-06 is a p38 MAP kinase inhibitor; inhibits p38α with an IC50 value of 170 nM and inhibits LPS-stimulated TNF-release in rats (83% inhibition at 1mg/kg, po). IC50 value: 170 nM Target: p38MAPK
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.