A Box of Chemistry to Inhibit the  MEN1 Tumor Suppressor Gene Promoting Leukemia.

A Box of Chemistry to Inhibit the MEN1 Tumor Suppressor Gene Promoting Leukemia.
ChemMedChem. 2021 Feb 03;:
Authors: Timmers HTM, Özyerli Göknar E, Nizamuddin S
Abstract
Targeting protein-protein interactions (PPIs) by small-molecule inhibitors has become the hotbed for modern drug development. In this review we describe a new class of PPI inhibitors, which block menin from binding to MLL proteins. Menin is encoded by the  MEN1  tumor suppressor, but it acts as an essential cofactor for  MLL/KMT2A  rearranged leukemias. The most promising menin-MLL inhibitors belong to the thienopyrimidine class and have recently entered phase I/II clinical trials to treat acute leukemias characterized by  MLL/KMT2A  translocations or  NPM1  mutations. As single agents thienopyrimidine compounds eradicate leukemia in a xenograft models of primary leukemic cells belonging to the  MLL  rearranged or NPM1-mutant subtypes. These compounds are well tolerated with little or no side effects, which is remarkable given the tumor suppressor function of menin. The menin-MLL inhibitors highlight how leukemia patients could benefit from a targeted epigenetic therapy with novel PPI inhibitors obtained by directed chemical evolution.
PMID: 33534953 [PubMed - as supplied by publisher]

Source: ChemMedChem - February 3, 2021 Category: Chemistry Authors: Timmers HTM, Özyerli Göknar E, Nizamuddin S Tags: ChemMedChem Source Type: research