PF-3644022

PF-3644022 is an inhibitor of MAPK-activated protein kinase 2 (MK2, IC50 = 5.2 nM). It is selective for MK2 over MK3, MAPK-interacting protein kinase 1 (MNK-1), MNK-2, p90 ribosomal S6 kinase 1 (MSK1), MSK2, and p90 ribosomal S6 kinases 1-4 (RSK1-4, IC50s = 53, 3,000, 148, >1,000, >1,000, and >1,000 nM, respectively), as well as a panel of 200 other kinases at 1 µM, but also inhibits MK5/PRAK (IC50 = 5 nM). PF-3644022 inhibits LPS-induced TNF-alpha production in U937 cells and isolated human peripheral blood mononuclear cells (PBMCs) and whole blood (IC50s = 0.159, 0.16, and 1.97 µM, respectively) and reduces paw swelling in a rat model of arthritis induced by streptococcal cell wall peptidoglycan-polysaccharide complexes (ED50 = 20 mg/kg). It prevents decreases in motor function in a twy/twy mouse model of chronic cervical spinal cord compression when administered at a dose of 30 mg/kg. Peritumoral administration of PF-3644022 (30 µl of a 50 µM solution) enhances radiation-induced decreases in tumor volume and increases in survival in a patient-derived xenograft (PDX) mouse model of head and neck squamous cell carcinoma (HNSCC).Formal Name: (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. CAS Number: 1276121-88-0. Molecular Formula: C21H18N4OS. Formula Weight: 374.5. Purity: >95%. Formulation: (Request formulation change), A solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, Ethanol: 3 mg/ml. lambdamax: 255, 287 nm. SMILES: CC1=CC=C(C2=CC=C(C(C(NC[C@@H](C)NC3=O)=C3S4)=C4C=C5)C5=N2)C=N1. InChi Code: InChI=1S/C21H18N4OS/c1-11-3-4-13(10-22-11)15-6-5-14-16(25-15)7-8-17-18(14)19-20(27-17)21(26)24-12(2)9-23-19/h3-8,10,12,23H,9H2,1-2H3,(H,24,26)/t12-/m1/s1. InChi Key: CMWRPDHVGMHLSZ-GFCCVEGCSA-N.