Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P10721 (
c-kit
)
6,575
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Hymenialdisine
(
HMD
) is a sponge-derived natural product kinase inhibitor with nanomolar activity against CDKs, Mek1, GSK3beta, and CK1 and micromolar activity against Chk1. In order to explore the broader application of the pyrrolo[2,3-c]azepine skeleton of
HMD
as a general kinase inhibitory scaffold, we searched for additional protein targets using affinity chromatography in conjunction with the synthesis of diverse
HMD
analogs and profiled
HMD
against a panel of 60 recombinant enzymes. This effort has led to nanomolar to micromolar inhibitors of 11 new targets including p90RSK, KDR,
c-Kit
, Fes, MAPK1, PAK2, PDK1, PKCtheta, PKD2, Rsk1, and SGK. The synthesis of
HMD
analogs has resulted in the identification of compounds with enhanced and/or dramatically altered selectivities relative to
HMD
(28n) and in molecules with antiproliferative activities 30-fold higher than
HMD
(28p).
...
PMID:Synthesis and target identification of hymenialdisine analogs. 1512 86
