DNMT2-IN-2 is a selective inhibitor of DNA methyltransferase 2 (DNMT2) with a KD value of 3.04 μM. It targets a concealed allosteric binding site of DNMT2 and reduces m5C levels in tRNA of MOLM-13 cells. This compound works synergistically with Doxorubicin to impair cell viability and is applicable in cancer research, including studies of cervical cancer and leukemia.

DNMT2:3.04 μM (Kd)

DNMT2-IN-2 (Compound 16) at a concentration of 50 μM for 72 hours significantly reduces the levels of target tRNA modifications (m 5 C and m 5 Cm) in MOLM-13 cells. At 50 μM for 16 hours, DNMT2-IN-2 provides thermal stabilization of DNMT2 in MOLM-13 cells. The compound exhibits low toxicity across a range of 1-100 μM for 48 hours in HCT 116, MOLM13, HEK293, MOLM-13, and Huh7 cells. Additionally, DNMT2-IN-2 at 50 μM for 6 days increases the sensitivity of MOLM-13, Huh-7, and MDA-MB-231 cells to Doxorubicin. Furthermore, at 50 μM for 45 minutes, DNMT2-IN-2 does not dissociate NonO or eIF4E from immobilized DNMT2.