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Formula | C22H19BrF2N2O3 |
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Molecular Weight | 477.3 | CAS No. | 586379-66-0 | |
Solubility (25°C)* | In vitro | DMSO | 96 mg/mL (201.13 mM) | |
Ethanol | 7 mg/mL (14.66 mM) | |||
Water | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
Description | PH-797804 is a novel pyridinone inhibitor of p38α with IC50 of 26 nM in a cell-free assay; 4-fold more selective versus p38β and does not inhibit JNK2. Phase 2. | ||||
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In vitro | PH-797804 blocks LPS-induced TNF-α production and p38 kinase activity in the human monocytic U937 cell line, with comparable IC50 of 5.9 nM and 1.1 nM. PH-797804 has no inhibitory effect on either the JNK pathway (c-Jun phosphorylation) or ERK pathway (ERK phosphorylation) in U937 cells at concentrations up to 1 μM. PH-797804 inhibits RANKL- and M-CSF-induced osteoclast formation in a concentration-dependent manner, with IC50 of 3 nM in primary rat bone marrow cells. [1] IC50 values for PH-797804 against the following targets have been determined to be greater than 200 μM (unless specified): CDK2, ERK2, IKK1, IKK2, IKKi, MAPKAP2, MAPKAP3, MKK7 (>100 μM), MNK, MSK (>164 μM), PRAK, RSK2, and TBK1, which means the activity of PH-797804 is specific. [2] | ||||
In vivo | Orally dosing of PH-797804 effectively inhibits acute inflammatory responses induced by systemically administered endotoxin in both rat and cynomolgus monkeys. PH-797804 treatment for 10 days demonstrates robust anti-inflammatory activity in chronic disease models, significantly reducing both joint inflammation and associated bone loss in streptococcal cell wall-induced arthritis in rats and mouse collagen-induced arthritis. Dose-response analysis resulted in ED50 values of 0.07 mg/kg and 0.095 mg/kg in rat and cynomolgus monkeys, respectively. PH-797804 inhibits LPS-induced TNF-α, IL-6, and MK-2 activity in a dose- and concentration-dependent manner in a human endotoxin challenge model. [1] |
Kinase Assay: |
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Data independently produced by , , Dr.Wang from Southern Medical Hospital
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SARS-CoV-2 spike protein-ACE2 interaction increases carbohydrate sulfotransferases and reduces N-acetylgalactosamine-4-sulfatase by p38 MAPK [ Signal Transduct Target Ther, 2024, 9(1):39] | PubMed: 38355690 |
Mitocurcumin utilizes oxidative stress to upregulate JNK/p38 signaling and overcomes Cytarabine resistance in acute myeloid leukemia [ Cell Signal, 2024, 114:111004] | PubMed: 38048856 |
Homoharringtonine enhances cytarabine-induced apoptosis in acute myeloid leukaemia by regulating the p38 MAPK/H2AX/Mcl-1 axis [ BMC Cancer, 2024, 24(1):520] | PubMed: 38658865 |
Coadaptation fostered by the SLIT2-ROBO1 axis facilitates liver metastasis of pancreatic ductal adenocarcinoma [ Nat Commun, 2023, 14(1):861] | PubMed: 36792623 |
HUWE1 controls tristetraprolin proteasomal degradation by regulating its phosphorylation [ Cell Biology, 2023, 10.7554/eLife.83159] | PubMed: None |
HUWE1 controls tristetraprolin proteasomal degradation by regulating its phosphorylation [ Elife, 2023, 12e83159] | PubMed: 36961408 |
Synthesis and Biological Activity of a VHL-Based PROTAC Specific for p38α [ Cancers (Basel), 2023, 15(3)611] | PubMed: 36765568 |
Synthesis and Biological Activity of a VHL-Based PROTAC Specific for p38α [ Cancers (Basel), 2023, 15(3)611] | PubMed: 36765568 |
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9] | PubMed: 35868306 |
Distinct histopathological phenotypes of severe alcoholic hepatitis suggest different mechanisms driving liver injury and failure [ J Clin Invest, 2022, 132(14)e157780] | PubMed: 35838051 |
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