MMPins

MMPins are a class of small-molecule inhibitors designed to disrupt the protein-protein interaction (PPI) between mitogen-activated protein kinase kinase 3 (MKK3) and the oncogenic transcription factor MYC. Developed by researchers at Emory University, these compounds target a novel mechanism of MYC activation identified through integrative bioinformatics. By disrupting the MKK3/MYC complex, MMPins destabilize the MYC protein and suppress its downstream transcriptional programs, including the expression of lactate dehydrogenase A (LDHA). This inhibition effectively blocks glycolytic reprogramming and metabolic adaptation in MYC-dependent tumors. Preclinical studies have demonstrated that MMPins can reduce cell viability in triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC) models. Furthermore, they have shown potential in reversing drug resistance, such as restoring apoptotic sensitivity in EGFR TKI-resistant NSCLC when combined with osimertinib.

Other names

MKK3/MYC protein-protein interaction inhibitorsMKK3/MYC PPI inhibitors