LY2940680

SKU: orb1226657

Description

LY2940680 (Taladegib) is potent Smoothened (SMO) receptor antagonist, potently inhibits Hedgehog (Hh) signaling with IC50 of 6.3 nM in Gli-luc reporter assyas; inhibits medulloblastoma cell proliferation isolated from Ptch+/–p53–/– mice with IC50 of 43.5 nM; demonstrates anti-tumor activity in vivo with advanced basal cell carcinoma (BCC) and other malignancies.Ovarian Cancer Phase 2 Clinical(In Vitro):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). 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.

Key Properties

• CAS Number: 1258861-20-9
• MW: 512.502
• Purity: >98% (HPLC)
• Formula: C₂₆H₂₄F₄N₆O
• 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
• Target: Smoothened (Smo)
• Solubility: DMSO: ≥ 5.2 mg/mL

Bioactivity

• In Vitro:
  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). 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

LY 2940680 | LY-2940680 | Taladegib

Quick Database Links

Gene Symbol

Smoothened (Smo)