EZH-2-IN-2

EZH2-IN-22 (example 92) is a potent EZH2 inhibitor, exhibiting IC50 values of <0.00051 µM for EZH2(Y641N) and EZH2(Y641F), and 0.00052 µM for EZH2 (wt). Additionally, EZH2-IN-22 demonstrates antiproliferative activity.

PARP/EZH2-IN-2 (compound 12e) functions as a dual inhibitor targeting both PARP1 and EZH2, with IC50 values of 6.89 and 27.34 nM, respectively. This compound exhibits anticancer activity without toxicity to normal cells, achieving synthetic lethality indirectly by increasing PARP1 sensitivity through EZH2 inhibition, and inducing cell death by modulating excessive autophagy.

EZH2-IN-23 (Compound 25) is an EZH2 inhibitor, exhibiting potent enzymatic inhibition against the PRC2 complex [EZH2, EED, SUZ12, AEBP2, and RbAp48] with an IC50 of 0.8 nM. It inhibits H3K27 trimethylation in cells with an IC50 of 40 nM. In rats, EZH2-IN-23 demonstrates excellent pharmacokinetic properties, achieving 100% oral bioavailability.

EZH2-IN-200 (compound 30) is an effective EZH2 (Enhancer of Zeste homologue 2) inhibitor with an IC50 of 11 nM against EZH2, suitable for studying hematologic malignancies and solid tumors.

EZH2-IN-3 is an inhibitor of EZH2 and EZH1 with selective impact on diffuse large B cell lymphoma cell growth.

EZH2-IN-5 is a highly effective inhibitor of EZH2, displaying remarkable potency against both wild-type and mutant Tyr641 EZH2, with IC50 values of 1.52 nM and 4.07 nM, respectively.

EZH2-IN-4 is a highly potent EZH2 inhibitor that can be taken orally. It exhibits inhibitory effects against wild type (WT) 5-membered (5-mer) EZH2 and mutant 5-mer EZH2, with IC 50 values of 0.923 nM and 2.65 nM, respectively. Moreover, EZH2-IN-4 has demonstrated significant anti-cancer activity.

PARP/EZH2-IN-1 is a novel dual inhibitor targeting PARP (IC50 6.87 nM) and EZH2 (IC50 36.51 nM), showing promising potential for treating triple-negative breast cancer with wild-type BRCA.

EZH2-IN-6 is an EZH2 inhibitor exhibiting enhanced antitumor activity.