Description
| Description | Nedisertib (M3814) (M3814) is a specific inhibitor of DNA-dependent Protein Kinase (DNA-PK, IC50: <3 nM). |
| Targets&IC50 | DNA-PK:<3 nM |
| In vitro | Nedisertib is a DNA-PK inhibitor, with an IC50 of <3 nM for DNA-PK and <0.5 μΜ for cellular pDNA-PK [2]. |
| In vivo | In combination with IR, Nedisertib shows efficacy in all of the 6 mouse models of human cancer. Nedisertib, alone or in combination with IR, does not induce significant weight loss or visual signs of toxicity in the mice in any study. In all models, a dose of 2 Gy administered daily for 1 week in combination with Nedisertib induces statically significant tumor growth inhibition to compare to IR alone [1]. |
| Animal Research | The efficacy of Nedisertib in combination with IR is evaluated in 6 human xenograft models (NCI-H460, A549, HCT116, FaDu, Capan-1, BxPC3) in mice representing 4 different cancer types (colon, head and neck, lung, and pancreas). Tumor cells are injected s.c. into nude mice, and treatment starts when palpable tumors are established (~100 to 200 mm^3 ). Nedisertib is given orally at different doses (25 to 300 mg/kg) 10 min prior to IR. IR is applied using a radiation therapy device for small rodents calibrated to deliver 2 Gy. Autophosphorylation of DNA-PK (serine2056) in FaDu tumor lysates is measured by immunoassay to assess pharmacological inhibition by Nedisertib [1]. |
| Synonyms | M3814 |
| Molecular Weight |
481.91 |
| Formula | C24H21ClFN5O3 |
| CAS No. | 1637542-33-6 |
Storage
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Solubility Information
DMSO: 100 mg/mL (207.51 mM),
Sonication is recommended.
H2O: Insoluble
