Ontology highlight
ABSTRACT:
SUBMITTER: Hammill JT
PROVIDER: S-EPMC5898815 | biostudies-literature | 2018 Apr
REPOSITORIES: biostudies-literature
Hammill Jared T JT Scott Daniel C DC Min Jaeki J Connelly Michele C MC Holbrook Gloria G Zhu Fangyi F Matheny Amy A Yang Lei L Singh Bhuvanesh B Schulman Brenda A BA Guy R Kiplin RK
Journal of medicinal chemistry 20180326 7
We previously discovered and validated a class of piperidinyl ureas that regulate defective in cullin neddylation 1 (DCN1)-dependent neddylation of cullins. Here, we report preliminary structure-activity relationship studies aimed at advancing our high-throughput screen hit into a tractable tool compound for dissecting the effects of acute DCN1-UBE2M inhibition on the NEDD8/cullin pathway. Structure-enabled optimization led to a 100-fold increase in biochemical potency and modestly increased sol ...[more]