Hh-Ag1.5 (SAg1.5) is a potent Hedgehog (Hh) agonist with an EC50 of 1 nM[1]. Hh-Ag1.5 mediated reprogramming breaks the quiescence of noninjured liver stem cells for rescuing liver failure[2].
HhAg1.5 (5 μM; for 3 weeks) facilitates dramatic expansion of quiescent CD133+ CD45- liver stem cells (Hh3A cells) enriched from non-injured liver in vitro[2]. Hh-Ag1.5 competely binds to the Smo-containing membranes with the Ki value of 0.52 nM[3].The Smo agonist SAG-1.5 displays nanomolar-range potency stimulation of Gli-responsive reporter activity, with an EC50 of 7 nM[4].
[1]. Randall W King. Roughing Up Smoothened: Chemical Modulators of Hedgehog Signaling. J Biol. 2002 Nov 6;1(2):8.
[2]. Abhisek Mitra, et al. A Small Molecule Hedgehog Agonist HhAg1.5 Mediated Reprogramming Breaks the Quiescence of Noninjured Liver Stem Cells for Rescuing Liver Failure. Transl Res. 2019 Mar;205:44-50.
[3]. Maria Frank-Kamenetsky, et al. Small-molecule Modulators of Hedgehog Signaling: Identification and Characterization of Smoothened Agonists and Antagonists. J Biol. 2002 Nov 6;1(2):10.
[4]. Cynthia M Rominger, et al. Evidence for Allosteric Interactions of Antagonist Binding to the Smoothened Receptor. J Pharmacol Exp Ther. 2009 Jun;329(3):995-1005.