1447463-75-3Relevant academic research and scientific papers
Structure-based design of flavone-based inhibitors of wild-type and T315I mutant of ABL
Choe, Hyeonjeong,Kim, Jieun,Hong, Sungwoo
supporting information, p. 4324 - 4327 (2013/07/25)
The existence of drug resistance caused by mutations in the break-point cluster region-Abelson (BCR-ABL) tyrosine kinase domain remains a clinical challenge due to limited treatment options for effective CML therapies. Here, we report a series of flavone-based common inhibitors equipotent for the wild type and the most drug-resistant T315I mutant of BCR-ABL. The original hit 1 was extensively modified through a structure-based drug design strategy, especially by varying the C7 acetamide appendage of the scaffold to exploit extended interactions with P-loop residues. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of ABL are discussed in detail.
