A cell-permeable oxo-tetrahydroquinolinecarboxylate compound that acts as a downstream Hh (Hedgehog) pathway blocker, effectively inhibiting Gli-dependent transcription activity in both
Sufu+/+ NIH 3T3 (shh-LIGHT2) and
Sufu-/- fibroblast cultures (IC
50 = 1.5 & 3 μM, respectively) in a manner similar to two other Hh downstream blockers, HPI-3 (Cat. No.
373276) and GANT-61 (Cat. No.
373401). However, only HPI-1, but not HPI-3 or GANT-61 (no effect at 30 μM), remains effective against
Sufu-/- fibroblasts overexpressing Gli1 or Gli2 (IC
50 = 6 & 4 μM, respectively). HPI-1 is also shown to inhibit the ligand-independent Hh pathway activation in SmoM2-expressing primary murine CGNPs (Cerebellar Granule Neuron Precursors) and NIH 3T3 (smoM2-LIGHT) cultures.