PAWI-2

PAWI-2 is a synthetic small molecule developed as a dual pathway modulator for anticancer therapy, specifically targeting human pancreatic cancer stem cells. It acts by simultaneously inhibiting Wnt signaling and activating p53, thereby blocking tumor stemness, reversing drug resistance, inducing cell cycle arrest, and inhibiting tumor proliferation and metastasis. PAWI-2’s mechanism involves modulation of mitotic assembly stress, interference in the integrin β3-KRAS signaling pathway, downstream inhibition of TBK1 phosphorylation with feedback via optineurin phosphorylation, and induction of p53-dependent apoptosis. Preclinical studies demonstrate that PAWI-2 inhibits tumor growth in orthotopic xenograft mouse models, works synergistically with erlotinib (an EGFR inhibitor), and exhibits promising efficacy with reduced toxicity in pancreatic, colon, prostate, and breast cancer models[1][2][3][5]. The developers anticipate that PAWI-2 may have further applications in other cancer indications pending clinical development.

Other names

PAWI-2PAWI2PAWI 2p53-Activator Wnt Inhibitor-2p-53-Activator Wnt Inhibitor-2p 53-Activator Wnt Inhibitor-2