LEQ506

LEQ506 is a second-generation inhibitor of smoothened (Smo) with IC50s of 2 and 4 nM in human and mouse, respectively.

Signaling Pathways >> Stem Cell/Wnt >> Smo

Research Areas >> Cancer

IC50: 2 nM (human smo), 4 nM (mouse smo)[1]

LEQ506 is a second-generation inhibitor of smoothened (Smo) with IC50s of 2 and 4 nM in human and mouse, respectively. LEQ506 inhibits Hedgehog (Hh) signaling in a human cell line (HEPM) as measured by the amount of Gli mRNA with an IC50 ~6-fold lower than that of Compound 2[1]. LEQ506 is an efficacious compound by consistently decreasing Gli1 mRNA by about 70 to 80%. LEQ506 shows a tendency to preferentially inhibit Gli1 rather than Ptch1 mRNA. LEQ506 (at 1%) is also an efficacious compound with an inhibition of 80 to 90% for Gli1 and of 60 to 70% for Ptch1[2].

DAOY cells are serum starved 16 h before experiments and subsequently incubated for 24 h with sonic Hedgehog (SHH) (50 nM) and LEQ506 at different concentrations. Cells are then washed twice with PBS and stored at -80°C until RNA isolation. Total RNA is isolated using the RNeasy Mini Kit. The amount and quality of extracted RNA are determined using the 2100 Bioanalyzer[2].

[1]. Peukert S, et al. Discovery of NVP-LEQ506, a second-generation inhibitor of smoothened. ChemMedChem. 2013 Aug;8(8):1261-5.

[2]. Lauressergues E, et al. Pharmacological evaluation of a series of smoothened antagonists in signaling pathways and after topical application in a depilated mouse model. Pharmacol Res Perspect. 2016 Mar 4;4(2):e00214.

SAG.HCI | Purmorphamine | LDE225 (NVP-LDE225,Erismodegib) | PF-04449913 | Jervine | LY2940680 | BMS-833923 | MK-4101 | MRT-83 | PF-5274857 | Saridegib