SSTC3

SSTC3 is a **small molecule activator of casein kinase 1α (CK1α)** with a dissociation constant (Kd) of 32 nM. SSTC3 effectively inhibits **WNT signaling (EC50 = 30 nM)** and is also described as a **potent HIF1α inhibitor** (Kd = 32 nM). It exhibits **antitumor activity** by suppressing tumor growth in several preclinical models, notably colorectal cancer (CRC) cell lines and Apc mutation-driven mouse models, as well as medulloblastoma, including SHH-subgroup models. SSTC3 acts downstream of SMO (Smoothened) and can overcome resistance mechanisms to SMO inhibitors, making it especially relevant for difficult-to-treat subsets such as *TRP53*-mutant, *MYCN*-amplified SHH medulloblastoma. Importantly, SSTC3 demonstrates improved pharmacokinetic properties over pyrvinium, including brain penetration, and exhibits minimal gastrointestinal toxicity compared to other WNT pathway inhibitors[1][2][3][4][5][6][7][8][10].