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HPI-1 (hydrate) is a Hedgehog (Hh) pathway inhibitor that suppresses signaling through Sonic Hh (IC50 = 1.5 μM) without significantly affecting Wnt signaling (IC50 ≥ 30 μM).1 HPI-1 suppresses Hh activation induced by loss of Suppressor of Fused or by Gli overexpression, suggesting action at posttranslational modification of Gli protein or at the interaction of Gli with a co-factor.1 HPI-1 (hydrate) also inhibits signaling through the oncogenic Smoothened (Smo) mutant SmoM2 in neuron precursors, preventing cell proliferation.1

1.Hyman, J.M., Firestone, A.J., Heine, V.M., et al.Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockadeProceedings of the National Academy of Sciences of the United States of America106(33)14132-14137(2009)

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