1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPH-797804Cat. No.: HY-10403CAS No.: 586379-66-0分式: CHBrFNO分量: 477.3作靶點(diǎn): p38 MAPK作通路: MAPK/ERK Pathway儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 50 mg/mL (104.76 mM; Need ultrasonic)Mas

2、s Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.0951 mL 10.4756 mL 20.9512 mL5 mM 0.4190 mL 2.0951 mL 4.1902 mL10 mM 0.2095 mL 1.0476 mL 2.0951 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn) 請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前?qǐng)先配制澄清的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百

3、分 指該溶劑在您配制終溶液中的體積占)：1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 3 mg/mL (6.29 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.24 mM); Clear solutionBIOLOGICAL ACTIVITY1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemE物活性 PH-797804 is a novel pyri

4、dinone inhibitor of p38 with IC50 of 26 nM; 4-fold more selective versus p38and does not inhibit JNK2.IC50 value: 26 nM 1Target: p38MAPKin vitro: PH-797804 blocks LPS-inducedTNF- production and p38 kinase activity in the human monocytic U937 cell line, with comparable IC50 of5.9 nM and 1.1 nM. PH-79

5、7804 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 M. PH-797804 inhibitsRANKL- and M-CSF-induced osteoclast formation in a concentration-dependent manner, with IC50 of 3 nMin primary rat bone mar

6、row cells 1. IC50 values for PH-797804 against the following targets have beendetermined to be greater than 200 M (unless specified): CDK2, ERK2, IKK1, IKK2, IKKi, MAPKAP2,MAPKAP3, MKK7 (100 M), MNK, MSK (164 M), PRAK, RSK2, and TBK1, which means the activity ofPH-797804 is specific 2. in vivo: Oral

7、ly dosing of PH-797804 effectively inhibits acute inflammatoryresponses 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 inflam

8、mation and associated bone loss in streptococcal cell wall-inducedarthritis in rats and mouse collagen-induced arthritis. Dose-response analysis resulted in ED50 values of0.07 mg/kg and 0.095 mg/kg in rat and cynomolgus monkeys, respectively. PH-797804 inhibits LPS-induced TNF-, IL-6, and MK-2 activ

9、ity in a dose- and concentration-dependent manner in a humanendotoxin challenge model 1.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Cell Death Dis. 2018 Apr 27;9(5):500. Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Hope

10、 HR, et al. Anti-inflammatory properties of a novel N-phenyl pyridinone inhibitor of p38 mitogen-activated protein kinase: preclinical-to-clinical translation. J Pharmacol Exp Ther, 2009, 331(3), 882-895.2. Xing L, et al. Structural bioinformatics-based prediction of exceptional selectivity of p38 MAP kinase inhibitor PH-797804. Biochemistry,2009, 48(27), 6402-6411.McePdfHeightCaution: Product has not been fully