CT1113

CT1113 is an orally bioavailable, small molecule inhibitor of the deubiquitinases ubiquitin-specific protease 28 (USP28) and ubiquitin-specific protease 25 (USP25), developed as a targeted anticancer agent. It binds USP28/USP25 with nanomolar potency and high selectivity, showing negligible activity on other deubiquitinases and SENP1, and leads to increased ubiquitination and proteasomal degradation of key oncogenic substrates including c-MYC, Tankyrase (TNKS), lysine-specific histone demethylase 1 (LSD1), and NOTCH1, as well as sterol regulatory element-binding protein 1 (SREBP1).[2][6][7][10] Through destabilization of these substrates, CT1113 rapidly reduces c-MYC levels, suppresses MYC-MAX target gene expression, impairs tumor cell proliferation, and induces apoptosis or cell cycle arrest across diverse cancer cell lines.[2][7] In multiple xenograft and CDX models (e.g., pancreatic and colon cancer), CT1113 demonstrates strong antitumor activity with associated reductions in MYC and Ki67, and acceptable tolerability in mice.[1][2][7] Preclinical work further shows that CT1113 inhibits growth of T-cell acute lymphoblastic leukemia (T-ALL) cells by destabilizing NOTCH1 and SREBP1, and has activity against Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) and mutant BCR-ABL1–expressing cells, supporting its development as a novel targeted therapy for hematologic malignancies and solid tumors.[5][6] Additional studies indicate that CT1113 can promote antitumor immunity, at least in part by modulating USP25/28–YTHDF2–mediated complement activation and enhancing responses to anti–PD-1 therapy in preclinical models.[4][8] A first-in-human clinical trial of CT1113 as a USP28 inhibitor in patients with advanced solid tumors has been initiated.[3]