YTHDF2-IN-1

YTHDF2-IN-1 (Compound CK-75) is a selective YTHDF2 inhibitor ( K d = 26.2 μM). YTHDF2-IN-1 binds to a small hydrophobic pocket on the YTH domain of YTHDF2, disrupting the interaction between YTHDF2 and m 6 A-modified RNA. YTHDF2-IN-1 induces cell cycle arrest and Apoptosis. YTHDF2-IN-1 is applicable to research on chronic myeloid leukemia, colon cancer and choriocarcinoma ^[1].

In Vitro, YTHDF2-IN-1 (100 μM; 30 min) inhibits the interaction between the purified YTHDF2 YTH domain and m6A RNA in FP assays, with an inhibition rate of 82.3% at a concentration of 100 μM^[1]. YTHDF2-IN-1 binds to the purified YTH domain of YTHDF2 in MST assays, with a Kd value of 26.2 μM^[1]. YTHDF2-IN-1 (10-25 μM; 24 h) induces concentration-dependent G0/G1 cell cycle arrest in K562 cells^[1]. YTHDF2-IN-1 (25-100 μM; 24 h) induces concentration-dependent apoptosis in K562 cells^[1]. YTHDF2-IN-1 (0.4-100 μM; 72 h) exhibits micromolar cytotoxicity against K562, HCT116 and JAR cancer cells in MTT assays, with corresponding IC₅₀ values of 29.7 μM, 33.3 μM and 47.5 μM after 72 h of treatment^[1].

References:
[1]. Qiu X, et al. Phenylpyrazoles as Inhibitors of the m 6 A RNA-Binding Protein YTHDF2. JACS Au. 2025;5(2):618-630. Published 2025 Feb 10.