HH2853

HH2853 (6 days) inhibits the proliferation of EZH2^G12C-mutant DLBCL cells, with an IC₅₀ value at the low nM level; however, it exhibits weak activity against EZH2 wild-type DLBCL cells (such as U-2932 and WILL-2), with an IC₅₀ value >10 μM^[1].
HH2853 (0.2-1 μM; 3-6 days) induces distinct molecular changes in both EZH2 inhibitor-insensitive (U-2932, WILL-2) and -sensitive (KARPAS-422, Pfeiffer) DLBCL cells: it upregulates H3K27ac, c-Myc, TfR-1, labile iron, GPX4, and HSPA5 in insensitive cells, while downregulating these markers in sensitive cells (with the exception of H3K27me3, which is reduced in all cell lines)^[1].
HH2853 (0.25-4 μM; 4-6 days) acts synergistically with ferroptosis inducers (RSL3 (HY-100218A); ML162 (HY-100002)) to trigger ferroptosis and reduce cell viability in U-2932, WILL-2, and OCI-LY10 diffuse large B-cell lymphoma (DLBCL) cells that are insensitive to EZH2 inhibitors; in contrast, GPX4 knockout restores the sensitivity of U-2932 cells to HH2853^[1].
HH2853 (4 h) potently inhibits the catalytic activity of wild-type EZH2, EZH2^G12C, and EZH1 in a cell-free HTRF assay, with IC₅₀ values ranging from 2.21 nM to 9.26 nM^[1].
HH2853 (compound 199) inhibits the methyltransferase activity of the EZH2 Y641F mutant, with an IC₅₀ ≤ 100 nM^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.