3MB-PP1

In several model organisms, the generation of conditional analog-sensitive kinase alleles has been developed as a chemical genetic strategy wherein a mutational enlargement of the ATP-binding site enables a protein kinase to interact with bulky ATP analogs.{28954,28952} Thus, a generic bulky ATP analog can competitively inhibit the activity of the mutant kinase, without interfering with the function of wild-type kinases whose ATP-binding pockets remain too small to accommodate the bulky analog. 3MB-PP1 is a bulky purine analog that acts as a selective, ATP-competitive, analog-sensitive polo-like kinase 1 (Plk1) allele inhibitor.{28953} At 10 µM, it can block mitotic progression in cells expressing analog-sensitive Plk1 alleles and has been used to selectively sensitize Plk1 to small-molecule inhibitors.{28952,28953}