Rapid synthesis of VX-745: p38 MAP kinase inhibition in Werner syndrome cells.
The p38 mitogen-activated protein kinase inhibitor VX-745 is prepared rapidly and efficiently in a four-step sequence using a combination of conductive heating and microwave-mediated steps. Its inhibitory activity was confirmed in hTERT immortalized HCA2 and WS dermal fibroblasts at 0.5-1.0 microM concentration by ELISA and immunoblot assay, and displays excellent kinase selectivity over the related stress-activated kinase JNK.
School of Chemistry, Main Building, Cardiff University, Park Place, Cardiff CF10 3AT, UK. Bagleymc@cardiff.ac.uk
Mark C
MC
Bagley
Terence
T
Davis
Matthew C
MC
Dix
Michal J
MJ
Rokicki
David
D
Kipling
D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D014898:Werner Syndrome / Q000201:enzymology* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
D047428:Protein Kinase Inhibitors; D011724:Pyridazines; D011743:Pyrimidines; D048051:p38 Mitogen-Activated Protein Kinases; C464966:VX-745