Carboxyamidotriazole Orotate

Carboxyamidotriazole Orotate (L-651582 Orotate) is the orotate salt form of Carboxyamidotriazole (CAI), an orally bioavailable signal transduction inhibitor. Carboxyamidotriazole Orotate is a cytostatic inhibitor of nonvoltage-operated calcium channels and calcium channel-mediated signaling pathways. Carboxyamidotriazole Orotate shows anti-tumor, anti-inflammatory and antiangiogenic effects[1][2].

Signaling Pathways >> Membrane Transporter/Ion Channel >> Calcium Channel

Research Areas >> Cancer

Research Areas >> Inflammation/Immunology

Carboxyamidotriazole Orotate (0.1-10 µM; 24-96 hours) inhibits cell proliferation of LAMA84R and K562R cell lines[1]. Carboxyamidotriazole Orotate inhibits the phosphorylation of a selected target of Bcr-Abl kinase. Tyrosine phosphorylation of CrkL is reduced by 5 µM Carboxyamidotriazole Orotate treatment[1]. Cell Viability Assay[1] Cell Line: LAMA84R and K562R cell lines Concentration: 0.1, 1, 5, 10 µM Incubation Time: 24, 48, 72, 96 hours Result: Showed a 50% growth reduction of the chronic myelogenous leukaemia (CML) lines with 5 µM CTO at 96 h time point. Western Blot Analysis[1] Cell Line: LAMA84R and K562R cell lines Concentration: 0.1, 1, 5 µM Incubation Time: 72 and 96 hours Result: A dose-dependent inhibition of both total and phosphorylated Bcr-Abl levels.

Carboxyamidotriazole Orotate (342, 513 mg/kg; i.p.; Q1D×5 for two rounds) displays antitumor activity on CML xenografts[1]. Animal Model: Male NOD/SCID mice four-to-five week old[1] Dosage: 342, 513 mg/kg Administration: i.p.; Q1D×5 for two rounds Result: Increase survival.

[1]. Corrado C, et al. Carboxyamidotriazole-orotate inhibits the growth of imatinib-resistant chronic myeloid leukaemia cells and modulates exosomes-stimulated angiogenesis. PLoS One. 2012;7(8):e42310.

[2]. Hussain MM, et al. Phase II trial of carboxyamidotriazole in patients with relapsed epithelial ovarian cancer. J Clin Oncol. 2003 Dec 1;21(23):4356-63.