193 D7

193 D7 is an inhibitor of the histone demethylase jumonji domain-containing 1C (JMJD1C).¹ It inhibits JMJD1C demethylation activity in vitro (IC₅₀ = 0.59 µM). It is selective for JMJD1C over 14 other histone demethylases, including JMJD1A and -1B (IC₅₀s = >100 µM for both), JMJD2A, -2B, -2C, -2D, and -2E (IC₅₀s = 24.7->100 µM), JMJD3 (IC₅₀ = 6.59 µM), JARID1A, -1B, and -1C (IC₅₀s = 14.61->100 µM), and UTX, PHF8, and LSD1 (IC₅₀s = 18.4->100 µM). 193 D7 (25 mg/kg per day) reduces tumor growth in mice bearing multiple types of subcutaneous tumors established using MCA-205 fibrosarcoma, B16/F10 melanoma, Hepa 1-6 hepatocellular, LLC lung, and CT26 colon cancer cells. It also reduces intratumoral levels of regulatory T cells (Tregs) and increases intratumoral levels of CD4⁺ and CD8⁺ tumor-infiltrating effector T cells in the same model.

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1. Long, X., Zhang, S., Wang, Y., et al. Targeting JMJD1C to selectively disrupt tumor Treg cell fitness enhances antitumor immunity. Nat. Immunol. 25(3), 525-536 (2024).