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Selective Bisubstrate Inhibitors with Sub‐nanomolar Affinity for Protein Kinase Pim‐1
Author(s) -
Ekambaram Ramesh,
Enkvist Erki,
Vaasa Angela,
Kasari Marje,
Raidaru Gerda,
Knapp Stefan,
Uri Asko
Publication year - 2013
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201300042
Subject(s) - kinase , conjugate , chemistry , biochemistry , computational biology , combinatorial chemistry , biology , mathematical analysis , mathematics
Potent and selective: The unique nature of the ATP binding pocket structure of Pim family protein kinases (PKs) was used for the development of bisubstrate inhibitors and a fluorescent probe with sub‐nanomolar affinity. Conjugates of arginine‐rich peptides with two ATP mimetic scaffolds were synthesized and tested as inhibitors of Pim‐1. Against a panel of 124 protein kinases, a novel ARC–PIM conjugate selectively inhibited PKs of the Pim family.