For research use only. Not for therapeutic Use.
Taladegib (LY2940680) is an antagonist of the smoothened receptor.
Taladegib, a small-molecule antagonist of the smoothened receptor, shows a slight inhibitory effect on cell proliferation without differences between mucin- (IC50: Taladegib=49.8±4.5 μM) and mixed- Cholangiocarcinoma (CCA) (IC50: Taladegib=61.2±21.1 μM)[1]. The IC50 for Taladegib inhibition of [3H]MRT-92 binding is right shifted (3- to 100-fold) for the S387AECL2, L325F3.36f, and D473H6.54f mutants but did not differ from that of WT receptor for the other mutants. The ability of SANT-1 to inhibit [3H]MRT-92 binding to V329F3.40f and T466F6.47f mutants is abolished, and it is severely impaired for L325F3.40f, I408F5.51f, and M525G7.45f mutants (4- to 140-fold drop of the IC50), but is not modified for the S387AECL2 mutant. Taken together, these data confirm our docking hypothesis that MRT-92-binding mode differs from that of either Taladegib or SANT-1 by simultaneously occupying binding sites 1 and 2[2].
| Catalog Number | I009693 |
| CAS Number | 1258861-20-9 |
| Synonyms | 4-fluoro-N-methyl-N-[1-[4-(2-methylpyrazol-3-yl)phthalazin-1-yl]piperidin-4-yl]-2-(trifluoromethyl)benzamide |
| Molecular Formula | C26H24F4N6O |
| Purity | ≥95% |
| InChI | InChI=1S/C26H24F4N6O/c1-34(25(37)20-8-7-16(27)15-21(20)26(28,29)30)17-10-13-36(14-11-17)24-19-6-4-3-5-18(19)23(32-33-24)22-9-12-31-35(22)2/h3-9,12,15,17H,10-11,13-14H2,1-2H3 |
| InChIKey | SZBGQDXLNMELTB-UHFFFAOYSA-N |
| SMILES | CN1C(=CC=N1)C2=NN=C(C3=CC=CC=C32)N4CCC(CC4)N(C)C(=O)C5=C(C=C(C=C5)F)C(F)(F)F |
| Reference | [1]. Fraveto A, et al, Sensitivity of Human Intrahepatic Cholangiocarcinoma Subtypes to Chemotherapeutics and Molecular Targeted Agents: A Study on Primary Cell Cultures. PLoS One. 2015 Nov 16;10(11):e0142124. [2]. Hoch L, et al. MRT-92 inhibits Hedgehog signaling by blocking overlapping binding sites in the transmembrane domain of the Smoothened receptor. FASEB J. 2015 May;29(5):1817-29. [3]. Ma W, et al. Reduced Smoothened level rescued Aβ-induced memory deficits and neuronal inflammation in animal models of Alzheimer’s disease. J Genet Genomics. 2018 May 20;45(5):237-246. |
