Erismodegib diphosphate (LDE225 diphosphate) is a potent and selective Smo antagonist with IC50 of 1.3 nM and 2.5 nM for mouse and human Smo in binding assay, respectively.
SMO-IN-2 (compound 1) is a potent smoothened (SMO) inhibitor with an IC50 value of 123.4 nM for hedgehog (Hh) signaling pathway. SMO-IN-2 has antiproliferative activity against human medulloblastoma cell line Daoy. Anticancer activity[1].
(Rac)-SAG is an isoform of SAG (HY-12848). SAG is a potent Smoothened (Smo) receptor agonist (EC50=3 nM; Kd=59 nM). SAG activates the Hedgehog signaling pathway and counteracts Cyclopamine (HY-17024) inhibition of Smo[1][2][3].
PF-5274857 is a potent and selective Smoothened (Smo) antagonist, inhibits Hedgehog (Hh) signaling with IC50 and Ki of 5.8 nM and 4.6 nM, respectively, and can penetrate the blood–brain barrier.IC50 value: 5.8 nMTarget: Smoothenedin vitro: PF-5274857 completely inhibits Shh-induced Hh pathway activity with IC50 of 2.7 nM measured by the transcriptional activity of Smo downstream gene Gli1 in MEF cells. The μ-opioid receptor is weakly inhibited by PF-5274857 with a dissociation constant of 36 μM subsequently determined in a functional assay [1].in vivo: PF-5274857 shows significant dose-dependent tumor growth inhibition (TGI) and induces tumor regression at high doses(>10 mg/kg)., PF-5274857 downregulates Gli1, Gli2, Ptch1, and Ptch2 gene expression levels to various degrees with maximal effects being achieved between 6 and 12 hours post-dose (Gli1 is the most sensitive gene), whereas PF-5274857 has little effect on Smo levels. In skin tissue, downregulation of Gli1 and Gli2 is also observed with a similar time course by PF-5274857. The model-derived drug concentration for half maximal inhibition of the tumor Gli1 mRNA production rate (IC50) by PF-5274857 is determined to be 8.9 nM in the Ptch+/?p53+/? medulloblastoma allograft mice, which mathematically corresponds to tumor regression of 119% TGI after 6 days of plasma exposure at this concentration. In the Ptch+/?p53?/? medulloblastoma allograft mice, the IC50 value is estimated to be 3.5 nM, consistent with the Ptch+/?p53+/? results. PF-5274857 is also able to cross the blood–brain barrier in rats within 4 hours post-dose [1].
SANT-1 is a potent Smo antagonist, inhibits Hedgehog signaling, with IC50s of 20 nM and 30 nM in Shh-LIGHT2 and SmoA1-LIGHT2 assay, respectively[1].