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KKB Hot Article: 2,4-Diaminopyrimidine MK2 inhibitors. Part II: Structure-based inhibitor optimization. |
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Written by KKB
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Tuesday, 20 April 2010 19:49 |
| Citation: 2,4-Diaminopyrimidine MK2 inhibitors. Part II: Structure-based inhibitor optimization. |
Authors: Harris CM, Ericsson AM, Argiriadi MA, Barberis C, Borhani DW, Burchat A, Calderwood DJ, Cunha GA, Dixon RW, Frank KE, Johnson EF, Kamens J, Kwak S, Li B, Mullen KD, Perron DC, Wang L, Wishart N, Wu X, Zhang X, Zmetra TR, Talanian RV.
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| PubMed PMID: 19926477 |
Abstract: We describe structure-based optimization of a series of novel 2,4-diaminopyrimidine MK2 inhibitors. Co-crystal structures (see accompanying Letter) demonstrated a unique inhibitor binding mode. Resulting inhibitors had IC(50) values as low as 19nM and moderate selectivity against a kinase panel. Compounds 15, 31a, and 31b inhibit TNFalpha production in peripheral human monocytes.
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Targets: AKT1, AKT2, AKT3,AURKA, AURKB, BLK, CDK1, CDK2, CDK4, CDK5 ,CHEK1, CHEK2, CHUK, CSF1R ,CSNK1D, DAPK3, DYRK1A, EGFR, FLT1, FLT3, FLT4, GSK3A, GSK3B, JAK3, LCK,L IMK1, MAPK12, MAPK13, MAPK8, MAPK9, MAPKAPK2, MAPKAPK3, MARK2, MARK3, PAK1, PAK4, PDK1, PIM1, PLK4, PRKAA2, PRKACA, PRKCD, PRKCG, PRKCZ, PRKD2, ROCK1, ROCK2, RPS6KA3, SGK1, SRC, STK3, TYK2
Number of SAR data points: 78
Number of Targets: 52
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Last Updated on Saturday, 20 August 2011 00:04 |
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