CDK2-IN-42 (Compound H63) is a CDK12 inhibitor with an IC50 of 10 nM. It exhibits activity against ESCC cells by blocking transcription elongation, downregulating core G1 phase genes to induce cell cycle arrest, and altering the CDK12-ATM/ATR-CHEK1/CHEK2 signaling pathway, leading to DNA damage. Additionally, CDK2-IN-42 effectively inhibits tumor growth in human ESCC KYSE150 xenograft mouse models, holding promise for cancer research.