Purmorphamine activates the Hedgehog pathway by targeting Smoothened.
Hedgehog (Hh) signaling is an important regulator of embryonic patterning, tissue regeneration, stem cell renewal and cancer growth. A purine derivative named purmorphamine was previously found to activate the Hh pathway and affect osteoblast differentiation through an unknown mechanism. We demonstrate here that purmorphamine directly targets Smoothened, a critical component of the Hh signaling pathway.
Sinha
Surajit
S
Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305, USA.
Chen
James K
JK
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D053823:Hedgehog Proteins; D051379:Mice; D009025:Morpholines / Q000494:pharmacology*; D041681:NIH 3T3 Cells; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D011687:Purines / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D000072086:Smoothened Receptor; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D023822:Tissue Engineering; D015534:Trans-Activators / Q000378:metabolism*; D014704:Veratrum Alkaloids / Q000494:pharmacology
D053823:Hedgehog Proteins; D009025:Morpholines; D011687:Purines; D043562:Receptors, G-Protein-Coupled; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D015534:Trans-Activators; D014704:Veratrum Alkaloids; C470893:purmorphamine; C000541:cyclopamine