Ontology highlight
ABSTRACT:
SUBMITTER: Cheng X
PROVIDER: S-EPMC8885691 | biostudies-literature | 2022 Feb
REPOSITORIES: biostudies-literature
Cheng Xiyao X Chen Rong R Zhou Ting T Zhang Bailing B Li Zichun Z Gao Meng M Huang Yongqi Y Liu Huili H Su Zhengding Z
Nature communications 20220228 1
Overexpressed Mdm2 and its 7homolog MdmX impair p53 activity in many cancers. Small molecules mimicking a p53 peptide can effectively inhibit Mdm2 but not MdmX. Here, we show a strategy for improving lead compounds for Mdm2 and MdmX inhibition based on the multivalency of the p53 peptide. Crystal structures of MdmX complexed with nutlin-3a, a strong Mdm2 inhibitor but a weak one for MdmX, reveal that nutlin-3a fits into the ligand binding pocket of MdmX mimicking the p53 peptide. However, due to ...[more]