Submission Details
Molecule(s):
C=CC(=O)Nc1cc(N(C)C)c(NCCC)cc1Nc1nccc(C(N)=O)n1
Design Rationale:
Acrylamide, loosely based on the Cys-modifying drug osimertinib. The compound was docked with the vinyl group in close proximity to Cys145 using the structure generated with the x0072 fragment (pdb 5R7Y). Docking and partial minimization was performed with Nanome (virtual reality). Two clefts are occupied by the dimethylamine and the propylamine moieties. There are multiple H bonds to Asn142 (involving the carbonyl oxygen of the amido group on the pyrimidine ring, the amine between the pyrimidine and phenyl rings, and the nitrogen of the acrylamide moiety).