EZH1 Inhibitor

Valemetostat (DS-3201), a first-in-class EZH1/2 dual inhibitor with IC₅₀ values ＜10 nM. Valemetostat can be used for the research of relapsed/refractory peripheral T-cell lymphoma.

UNC1999, a chemical probe, is a SAM-competitive, potent and selective inhibitor of EZH2/1 with IC₅₀s of <10 nM and 45 nM, repectively.

Valemetostat (DS-3201) tosylate, a first-in-class EZH1/2 dual inhibitor with IC₅₀ values ＜10 nM. Valemetostat tosylate can be used for the research of relapsed/refractory peripheral T-cell lymphoma.

Tulmimetostat (CPI-0209) is an orally active EZH1/EZH2 inhibitor that targets and inhibits the EZH2 enzyme.Tulmimetostat has antitumor activity and is used in a variety of solid tumor studies.

(S)-HH2853 (compound 200), a PYRIDINO five membered aromatic ring compound, is a potent EZH1/2 dual inhibitor with an IC₅₀ of <100 nM for EZH2_Y641F. (S)-HH2853 has the potential to be used in the research of anti-tumor or autoimmune diseases.

NSD2-IN-6 is a selective and orally active ^NSD2 inhibitor with IC₅₀s of 3.8  and 274 nM for ^NSD2 and ^NSD1 respectively. NSD2-IN-6 reduces H3K36me2 levels, reverses cell plasticity by restoring the androgen receptor (^AR) signaling pathway. NSD2-IN-6 reduces a shift from cluster 2 and 3 states towards the cluster 1 state in organoids. NSD2-IN-6 exerts antitumor activity by reversing tumor cell plasticity, suppressing growth, and promoting ^apoptosis in vivo. NSD2-IN-6 can be used for prostate cancer research.

HH2853 is an orally active EZH1/EZH2 inhibitor, with an IC₅₀ of 9.26 nM for EZH1 and IC₅₀ values ranging from 2.21 to 3.75 nM for both wild-type and mutant EZH2. HH2853 simultaneously inhibits the methyltransferase activities of EZH1 and EZH2, blocks the compensatory pathway that arises following EZH2 inhibition, and reduces H3K27me3 levels. HH2853 upregulates the expression of c-Myc and TfR-1 to induce intracellular iron accumulation, and stabilizes GPX4 via HSPA5 to suppress ferroptosis. HH2853 combined with Erastin (HY-15763) synergistically inhibits EZH2 wild-type DLBCL cell proliferation. HH2853 alone shows weak activity against EZH2 wild-type DLBCL and is well tolerated. HH2853 is applicable for research related to diffuse large B-cell lymphoma, non-Hodgkin's lymphoma, epithelioid sarcoma, and follicular lymphoma.