HPI-1

HPI-1 (Hedgehog Pathway Inhibitor 1) is a potent small molecule inhibitor of the Hedgehog (Hh) signaling pathway that acts downstream of the Smoothened (SMO) receptor. It specifically targets the GLI transcription factors, primarily GLI1 and GLI2, which are the terminal effectors of the Hh pathway. By inhibiting GLI activity, HPI-1 suppresses the transcription of oncogenic target genes involved in tumor growth, epithelial-mesenchymal transition (EMT), and the activation of cancer-associated fibroblasts (CAFs). Preclinical research has demonstrated that HPI-1 can significantly reduce the expression and secretion of osteopontin (OPN/SPP1) in bone metastatic breast cancer models, thereby disrupting the positive feedback loop known as the 'vicious cycle' of bone metastasis and potentially mitigating drug resistance to chemotherapeutics like paclitaxel.

Other names

2-(2-oxo-2-phenylethyl)-3H-thieno[3,2-d]pyrimidin-4-one