EHMT2/G9a/KMT1C Degrader

MS8709 is a PROTAC degrader that induces the degradation of G9a (EHMT2)/GLP (EHMT1) by recruiting VHL. MS8709 induces G9a/GLP protein degradation via a mechanism that simultaneously depends on G9a/GLP target protein binding, VHL recruitment, and the ubiquitin-proteasome system (UPS), while the mRNA levels of G9a and GLP do not show significant changes, indicating that the effect occurs primarily at the protein level rather than the transcriptional level. MS8709 retains the inhibitory effect on G9a/GLP methyltransferase activity and reduces H3K9me2 levels, thereby simultaneously affecting the catalytic and non-catalytic functions of G9a/GLP. MS8709 can be used for studies related to G9a/GLP biology, prostate cancer, lung cancer, and other relevant fields.

PROTAC G9a/GLP degrader 1 is a PROTAC degrader targeting G9a/GLP histone methyltransferases, with DC₅₀ values of 336 nM and 988 nM against G9a and GLP, respectively. PROTAC G9a/GLP degrader 1 reduces H3K9me2 levels, inhibits breast cancer cell migration, and has no effect on cell viability. PROTAC G9a/GLP degrader 1 can be used in breast cancer-related research.

MS4322 (YS43-22) is a specific PRMT5 PROTAC degrader. MS4322 reduces the PRMT5 protein level with a DC₅₀ of 1.1 μM in MCF-7 cells. MS4322 inhibits the methyltransferase activity of PRMT5 with an IC₅₀ of 18 nM. MS4322 promotes ubiquitination and degradation of PRMT5. MS4322 can be used for the research of breast cancer, lung cancer, and hepatocellular cancer. (Pink: PRMT5 ligand (HY-173092); Blue: E3 ligase ligand HY-112078); Black: linker (HY-124780); E3+linker (HY-173093 )).

PROTAC G9a degrader-1 is a selective and orally active G9a PROTAC degrader with a DC₅₀ of 1.29 μM. PROTAC G9a degrader-1 inhibits the NF-κB signaling pathway, suppresses the proliferation and migration of cancer cells, promotes apoptosis and cell cycle arrest, and reduces the expression level of H3K9me2. In in vivo models, PROTAC G9a degrader-1 alleviates skin inflammation, reduces epidermal hyperplasia, and decreases Ki67 expression. PROTAC G9a degrader-1 can be used for the research of triple-negative breast cancer and psoriasis.