basroparib (STP1002)

The compound also enhanced MEK inhibitor efficacy in other YAP-active tumor types, while exerting minimal effects in YAP-inactive models. Taken together, these results identify basroparib-now progressing through clinical development (Phase I, NCT04505839)-as a promising agent for dual Wnt-YAP pathway blockade and for overcoming therapeutic resistance in YAP-driven cancers.

Among them, 11b (STP1002, Basroparib) demonstrated the most favorable profile, with sub-nanomolar IC50 values for TNKS1/2, high selectivity, and excellent physicochemical and ADME properties. These findings support the further development of STP1002 as a promising therapeutic candidate for Wnt-driven cancers, with potential applications as both a monotherapy and in combination with other targeted agents.

Basroparib (STP1002) was shown to be a safe and well-tolerated tankyrase-selective inhibitor with preliminary anti-tumor activity warranting further investigation.

Mechanistically, basroparib suppressed Wnt-mediated cancer stemness, a bypass mechanism for acquired resistance to MEK inhibitors in KRAS-mutated CRC. This study provides the first preclinical evidence of the relevance of basroparib in treating CRC with acquired resistance to MEK inhibitors due to APC and KRAS mutations, possibly by reducing the Wnt-mediated cancer stemness.

P1, N=32, Completed, ST Pharm Co., Ltd. | Active, not recruiting --> Completed

These results demonstrate that STP1002, a novel, orally active tankyrase inhibitor, shows preclinical antitumour efficacy without on-target toxicity in the GI tract. Our data provide a rationale for a clinical trial on STP1002 as a potential tankyrase-targeted drug in patients with APC-mutated CRC.