Kintor Pharma", HKEX: 9939.HK), a clinical-stage biotechnology company developing innovative small molecule and biological therapeutics, announces that Kintor and its cooperative partner had published an article named MYCMYC Induces CDK4/6 Inhibitors Resistance by Promoting pRB1 Degradation in a subsidiary journal of Nature—Nature Communications (Impact factor: 16.6). Nature Communications is one of the top journals in biology field and is classified as Q1 in several categories, representing a leading research level in the world. The study shows that target c-Myc molecular glue compound has great potential, which could provide more directions for overcoming resistance issues of CDK4/6 inhibitors in various tumor fields. High MYC expression drives resistance to CDK4/6i by masking pRB1 High MYC expression reduces pRB1 abundance via proteasomal degradation The E3 ubiquitin ligase KLHL42 interacts with pRB1 and induces pRB1 proteasomal degradation KLHL42 is a transcriptional target of MYC that mediates CDK4/6i resistance Identification of A80.2HCl as a MYC-degrading molecule High MYC expression drives resistance to CDK4/6i by directly activating the transcription of the E3 ubiquitin ligase KLHL42, which promotes pRB1 ubiquitination and degradation and thus leads to pRB1 protein deficiency A molecule that degrades MYC, A80.2HCl, developed by Kintor Pharma, to abolish MYC when applied at nanomolar levels, rescues pRB1 protein activity, and diminishes MYC-dependent CDK4/6i resistance The combination of CDK4/6i and MYC-degrading molecule A80.2HCl shows an additive effect on killing tumor cells both in vitro and in vivo The full article is available in Nature Communications.
Download: https://www.nature.com/articles/s41467-024-45796-w