Gartisertib (VX-803) is an orally active, ATP-competitive, and selective inhibitor of ATR, with a Ki value of <150 pM. It effectively suppresses ATR-driven phosphorylation of checkpoint kinase-1 (Chk1) with an IC50 of 8 nM. It also demonstrates significant antitumor activity [1][2].
体内研究
In efficacy studies as a monotherapy, Gartisertib demonstrates tumor stasis to regression in tumor models characterized by alternative lengthening of telomeres (ALT). When combined with PARP inhibitors, tumor regression is observed in xenograft models of triple-negative breast cancer [1].
Gartisertib 细胞实验
Cell Line
Concentration
Treated Time
Description
References
U-2 OS cells
1 μM
30 minutes
Evaluate the effect of ATR inhibition on DNA damage response
Mol Cell Proteomics. 2024 Aug;23(8):100802.
U-2 OS cells
1 μM
1 hour
Inhibit ATR activity and block CHK1 Ser345 phosphorylation
Mol Cell Proteomics. 2024 Aug;23(8):100802.
Glioblastoma cell lines
1 μM
7 days
To evaluate the cytotoxicity of Gartisertib alone, results showed that Gartisertib significantly reduced the viability of glioblastoma cells.
Oncotarget. 2024 Jan 16;15:1-18.
786-O
125 nM and 250 nM
48 hours
Induced DNA damage accumulation in S phase cells
JCI Insight. 2022 Dec 22;7(24):e156087.
786-O
200 nM and above
24 hours
Induced S phase arrest
JCI Insight. 2022 Dec 22;7(24):e156087.
Gartisertib 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
786-O and A498 xenograft models
Oral
10 mg/kg or 20 mg/kg
Once daily
Significantly decreased tumor growth rates and final tumor sizes
JCI Insight. 2022 Dec 22;7(24):e156087.
Mouse
HBCx-9 PDX tumor model
Oral
3 mg/kg
Once daily for 35 days
To evaluate the antitumor efficacy of Gartisertib in combination with PARP inhibitors, showing that combination therapy was more effective than monotherapy.
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