GT1708

GT1708 is a potent, clinical-stage small molecule inhibitor of the Hedgehog (HH) signaling pathway, developed by Kintor Pharmaceuticals. It targets the HH/GLI signaling axis, which is essential for embryonic development and the maintenance of stem cells, including leukemic stem cells in Acute Myeloid Leukemia (AML). GT1708 exhibits high potency with an IC50 of 0.11 nM in HH pathway-driven cellular assays and has been shown to inhibit GLI expression in medulloblastoma animal models. In AML models, GT1708 down-regulates the anti-apoptotic protein MCL-1, thereby enhancing the apoptotic effects of BCL-2 inhibitors like venetoclax and potentially overcoming resistance to venetoclax/hypomethylating agent (HMA) combinations. GT1708 is currently being evaluated in a Phase I clinical trial for patients with relapsed or refractory AML, where it has demonstrated a favorable safety profile and preliminary signs of activity, such as reduction in blast counts.