| Identification | Back Directory | [Name]
vx984 | [CAS]
1476074-39-1 | [Synonyms]
vx984
vx-984
VX-984 (M9831)
M9831 free base
VX-984 (Synonyms: M9831)
(S)-N-Methyl-8-(1-((2'-methyl-[4,5'-bipyrimidin]-6-yl-4',6'-d2)amino)propan-2-yl)quinoline-4-carboxamide | [Molecular Formula]
C23H21D2N7O | [MDL Number]
MFCD30502668 | [MOL File]
1476074-39-1.mol | [Molecular Weight]
415.487 |
| Hazard Information | Back Directory | [Uses]
VX-984 is an orally active, potent, selective and BBB-penetrated DNA-PK inhibitor. VX-984 efficiently inhibits NHEJ (non-homologous end joining) and increases DSBs (DNA double-strand breaks). VX-984 can be used for glioblastomas (GBM) and non-small cell lung cancer (NSCLC) research. VX-984 is a de novo deuterium[1][2][3]. | [in vivo]
VX-984 (0-100 mg/kg, Oral gavage, daily) inhibits radiation-induced DNA-PKcs phosphorylation in orthotopic brain tumor xenografts[1].
VX-984 (0-50 mg/kg, Oral gavage, twice a day for 2 days) enhances the radiosensitivity of brain tumor xenografts[1]. | Animal Model: | Athymic female nude mice (6-8 weeks old, 7-8 mice/group, U251 intracerebral xenografts)[1] | | Dosage: | 0, 50, and 100 mg/kg | | Administration: | Oral gavage, daily, 1 or 4 hours before irradiation (10 Gy) | | Result: | Reduced the levels DNA-PKcs phosphorylation after irradiation. |
| Animal Model: | Athymic female nude mice (6-8 weeks old, 7 mice/group, U251 intracerebral xenografts)[1] | | Dosage: | 0, 50 mg/kg | | Administration: | Oral gavage, twice a day, 30 minutes before and 4 hours following local irradiation of the tumor (3 Gy) for 3 consecutive days (3×3 Gy) | | Result: | VX-984 treatment of U251 tumors alone had no significant effect on overall survival as compared with vehicle; radiation alone resulted in an increase in survival. VX-984 and radiation combination protocol increased tumor radiosensitivity, and significantly increased the survival of mice compared with radiation alone. |
| [References]
[1] Timme CR, et al. The DNA-PK Inhibitor VX-984 Enhances the Radiosensitivity of Glioblastoma Cells Grown In Vitro and as Orthotopic Xenografts. Mol Cancer Ther. 2018 Jun;17(6):1207-1216. DOI:10.1158/1535-7163.MCT-17-1267
[2] Khan AJ, et al. VX-984 is a selective inhibitor of non-homologous end joining, with possible preferential activity in transformed cells. Oncotarget. 2018 May 25;9(40):25833-25841. DOI:10.18632/oncotarget.25383
[3] Diane Boucher, et al. Abstract 3716: Potent radiation enhancement with VX-984, a selective DNA-PKcs inhibitor for the treatment of NSCLC. Cancer Res (2016) 76 (14_Supplement): 3716.
[4] Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216. DOI:10.1177/1060028018797110 |
|
|