| Identification | Back Directory | [Name]
PF 3644022 | [CAS]
1276121-88-0 | [Synonyms]
PF 3644022
MK2 INHIBITOR
(10R)-9,10,11,12-Tetrahydro-10-Methyl-3-(6-Methyl-3-pyridinyl)-8H-[1,4]diazepino[5',6':4,5]thieno[3,2-f]quinolin-8-one
8H-[1,4]Diazepino[5',6':4,5]thieno[3,2-f]quinolin-8-one, 9,10,11,12-tetrahydro-10-methyl-3-(6-methyl-3-pyridinyl)-, (10R)- | [Molecular Formula]
C21H18N4OS | [MDL Number]
MFCD22683806 | [MOL File]
1276121-88-0.mol | [Molecular Weight]
374.46 |
| Chemical Properties | Back Directory | [Melting point ]
>180°C (dec.) | [Boiling point ]
703.3±60.0 °C(Predicted) | [density ]
1.298±0.06 g/cm3(Predicted) | [storage temp. ]
Keep in dark place,Sealed in dry,2-8°C | [solubility ]
DMSO (Slightly), Methanol (Slightly) | [form ]
Solid | [pka]
13.51±0.40(Predicted) | [color ]
Off-White to Yellow |
| Hazard Information | Back Directory | [Uses]
PF-3644022 is a potent freely reversible ATP-competitive compound that inhibits MK2 activity (Ki = 3 nM) with good selectivity when profiled against 200 human kinases. PF-3644022 is a benzothiophene inhibitor of mitogen-activated protein kinase-activated protein kinase 2 inhibits tumor necrosis factor α production and has oral anti-inflammatory efficacy in acute and chronic models of inflammation. | [Biological Activity]
pf-3644022 is a potent and selective mitogen-activated protein kinase (mapk)-activated protein kinase-2 (mk2) inhibitor (ki =3 nm). [1]pf-3644022 is the first oral mk2 inhibitor in both acute and chronic models of inflammation. pf-3644022 reversibly atp-competitive inhibits mk2 enzyme activity with good selectivity across 200 human kinases. [1]in the human u937 monocytic cell line or peripheral blood mononuclear cells, pf-3644022 potently inhibits tnf production with ic50 value of 160 nm. in lps-stimulated human whole blood, pf-3644022 blocks tnf and il-6 production with ic50 values of 1.6 and 10.3 μm, respectively. in u937 cells and blood, inhibition of tnf correlates closely with inhibition of phospho-heat shock protein 27, a target biomarker of mk2 activity. [1]in the rat lps-induced tnf model, pf-3644022 efficacy in the chronic inflammation model is strongly correlated with maintaining a cmin higher than the ec50 measured. pf-3644022 exhibits efficaciously oral activity and good pharmacokinetic parameters in both the chronic streptococcal cell wall-induced arthritis model and the rat acute lps-induced tnf model. [1] | [in vivo]
PF-3644022 (3-100 mg/kg; oral gavage; twice a day; for 12 days; Lewis rats) treatment shows dose-dependent inhibition of chronic paw swelling measured on day 21 after 12 days of oral dosing, with ED50 value of 20 mg/kg[1]. | Animal Model: | Female Lewis rats (125-140 g) injected with streptococcal cell wall[1] | | Dosage: | 3 mg/kg, 10 mg/kg, 30 mg/kg, 50 mg/kg, 100 mg/kg | | Administration: | Oral gavage; twice a day; for 12 days | | Result: | Showed dose-dependent inhibition of chronic paw swelling measured on day 21 after 12 days of oral dosing.
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| [storage]
Store at +4°C | [References]
1. mourey rj, burnette bl, brustkern sj et al. a benzothiophene inhibitor of mitogen-activated protein kinase-activated protein kinase 2 inhibits tumor necrosis factor alpha production and has oral anti-inflammatory efficacy in acute and chronic models of inflammation. j pharmacol exp ther. 2010 jun;333(3):797-807. doi: 10.1124/jpet.110.166173. epub 2010 mar 17. |
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Sigma-Aldrich
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021-61415566 800-8193336 |
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https://www.sigmaaldrich.cn |
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