LY2940680 is a Hedgehog inhibitor in clinical trials. LY2940680 binds to the Smo receptor and potently inhibits Hh signaling. LY2940680 inhibits cancer growth in cell lines containing a mutation in the gene encoding Smoothened that researchers had previously observed in patient with cancer who developed resistance to vismodegib. LY2940680 induces Caspase-3 activity and reduces proliferation by immunohistochemistry analysis of medulloblastoma tumors. LY2940680 is currently being tested in phase I trials for people with a range of solid tumors.
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Source | PLoS One (2015). Figure 3. LY2940680 |
| Method | MTS assay | |
| Cell Lines | CCA Cell | |
| Concentrations | 50 μM | |
| Incubation Time | 72 h | |
| Results | In contrast, Vismodegib, a small-molecule antagonist of Smoothened and LY2940680, a small-molecule antagonist of the smoothened receptor, showed a slight inhibitory effect on cell proliferation without differences between mucin-(IC50: Vismodecib = 61.7 ± 1.4 μM, LY2940680 = 49.8 ± 4.5 μM) and mixed-CCA (IC50: Vismodecib = 81.6 ± 14.8 μM, LY2940680 = 61.2 ± 21.1 μM). |
| Molecular Weight | 512.5 |
| Formula | C26H24F4N6O |
| CAS Number | 1258861-20-9 |
| Solubility (25°C) | DMSO 10 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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