MS1943 represents a pioneering orally bioavailable EZH2 selective degrader, demonstrating an IC50 value of 120 nM. It notably diminishes EZH2 protein levels across various triple-negative breast cancer (TNBC) and other cancer and noncancerous cell lines. Additionally, MS1943 robustly impedes the proliferation of multiple TNBC and other cancer cell lines[1].
体内研究
MS1943 (150 mg/kg body weight; i.p.; once daily for 36 days) inhibits tumor growth[1].
MS1943 triggers apoptosis in the MDA-MB-468 xenograft model[1].
A sole intraperitoneal (i.p.) administration of MS1943 at 50 mg/kg body weight led to a peak plasma concentration (Cmax) of 2.9 µM, maintaining plasma concentrations above its cellular IC50 value for approximately 2 hours. Conversely, a single oral (p.o.) dose of 150 mg/kg body weight yielded a Cmax of 1.1 µM, with plasma concentrations falling below the cellular IC50 value[1].
体外研究
MS1943 (0.625-5 μM; 3 days) suppresses cell growth, yielding a GI50 value of 2.2 µM[1].
MS1943 (0.625-5 μM; 4 days) triggers cell death in MDA-MB-468 cells. Additionally, MS1943 efficiently decreases EZH2 levels in BT549, HCC70, and MDA-MB-231 TNBC cells, as well as in KARPAS-422 and SUDHL8 lymphoma cells, and PNT2 non-cancerous prostate cells[1].
MS1943 (1.25-5.0 μM; 2 days) decreases EZH2 and SUZ12 protein levels in a concentration- and time-dependent manner, while EED protein levels remain unaffected. Additionally, the H3K27me3 mark is suppressed[1].
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