| Description: |
MS1943 is a first-in-class, orally bioavailable EZH2 selective degrader, with an IC50 of 120 nM. MS1943 significantly reduces EZH2 protein levels in numerous triple-negative breast cancer (TNBC) and other cancer and noncancerous cell lines. MS1943 effectively blocks proliferation of multiple TNBC and other cancer cell lines[1]. |
| Target: |
EZH2:120 nM (IC50) |
| In Vivo: |
MS1943 (150 mg/kg body weight; i.p.; once daily for 36 days) suppresses tumor growth[1]. MS1943 induces apoptosis in the MDA-MB-468 xenograft model[1]. A single i.p. injection of MS1943 at 50 mg/kg body weight achieved a peak plasma concentration (Cmax) of 2.9 µM and resulted in plasma concentrations above its cellular IC50 value for ~2h. A single 150 mg/kg body weight p.o. dose achieved Cmax of 1.1 µM, but plasma concentrations were below the cellular IC50 value[1]. Animal Model: Eight-week-old female BALB/c nude mice (MDA-MB-468 xenografts)[1] Dosage: 150 mg/kg body weight Administration: i.p.; once daily for 36 days Result: Suppresses tumor growth. |
| In Vitro: |
MS1943 (0.625-5 μM; 3 days)inhibits cell growth with an GI50 of 2.2 µM[1]. MS1943 (0.625-5 μM; 4 days)induces cell death in MDA-MB-468 cells. MS1943 effectively reduces EZH2 levels in BT549, HCC70 and MDA-MB-231 TNBC cells, as well as KARPAS-422 and SUDHL8 lymphoma cells and PNT2 non-cancerous prostate cells[1]. MS1943 (1.25-5.0μM; 2 days) inhibits EZH2 and SUZ12 protein levels in a concentration- and timedependent manner, without affecting EED protein levels, whereas the H3K27me3 mark was also suppressed[1]. Cell Viability Assay[1] Cell Line: MDA-MB-468 cells Concentration: 0.625, 1.25, 2.5, 5 μM Incubation Time: 3 days Result: Inhibits cell growth with an GI50 of 2.2 µM. Western Blot Analysis[1] Cell Line: MDA-MB-468 cells Concentration: 1.25, 2.5, 5.0 μM Incubation Time: 2 days Result: Reduced EZH2 protein levels in a concentration- and time-dependent manner. |
| References: |
[1]. Ma A, et al. Discovery of a first-in-class EZH2 selective degrader.Nat Chem Biol. 2020 Feb;16(2):214-222. |
