JMJD1C-IN-1 is an orally active and selective inhibitor of JMJD1C ( IC 50 = 0.59 μM, K d = 1.96 μM). JMJD1C-IN-1 inhibits the binding of JMJD1C to H3K9me2 peptide substrate in the HTRF assay ( IC 50 = 1.47 μM). JMJD1C-IN-1 disrupts intratumoral regulatory T (Treg) cell fitness by dual mechanisms: promoting H3K9me2 accumulation to downregulate PD1 expression and reducing STAT3 demethylation to enhance STAT3 activation. JMJD1C-IN-1 demonstrates dose-dependent antitumor efficacy in multiple mouse tumor models (MCA205 fibrosarcoma, B16-F10 melanoma, LLC lung cancer , Hepa1-6 hepatocellular carcinoma, CT26 colorectal cancer ). JMJD1C-IN-1 can be used for the study of tumor immunotherapy by selectively targeting intratumoral Treg cells.
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