Background:

Carglumic acid (N-Carbamyl-L-glutamic acid), a functional analogue of N-acetylglutamate (NAG) and a carbamoyl phosphate synthetase 1 (CPS1) activator, is used to treat acute and chronic hyperammonemia associated with NAG synthase (NAGS) deficiency.

Carglumic acid suppresses cell viability in the pancreatic ductal adenocarcinoma cell lines, triple-negative breast cancer cell lines, hepatoma cell lines, and human non-small cell lung carcinoma cell lines in a dose-dependent manner. The 50% inhibitory concentration (IC50) of Carglumic acid against those cell lines is between 5 and 7.5 mM. The results show that Carglumic acid does not induce complete cell cycle arrest. Instead, there are more sub-G1 cells among Carglumic acid-treated AsPC1 and MDA-MB-231 cells than among untreated cells. In AsPC1 and HPDE-E6E7 cells, the IC50s of Carglumic acid are 5 mM and over 10 mM, respectively . In MDA-MB-231 and MCF-12A cells, the IC50s of Carglumic acid are 5 mM and 6 mM, respectively[1].

The results show that Carglumic acid, but not the vehicle control, markedly inhibits tumor growth. In the orthotopic pancreatic cancer model, tumor growth inhibition by Carglumic acid on day 21 is 80% (P<0.01). In the orthotopic triple-negative breast cancer model, tumor growth inhibition by Carglumic acid on day 20 is 82% (P<0.01). These results indicate that Carglumic acid suppresses tumor growth in pancreatic cancer and triple-negative breast cancer. On day 20, mean tumor growth inhibition in orally and intravenously treated mice is 55% and 93%, respectively, relative to untreated mice (P<0.01)[1].

参考文献:
[1]. Chen CT, et al. Carglumic acid promotes apoptosis and suppresses cancer cell proliferation in vitro and in vivo. Am J Cancer Res. 2015 Nov 15;5(12):3560-9.