C75

C75 is a specific inhibitor of fatty acid synthase (FASN/FAS) with moderate inhibitory activity, showing an IC50 value of 15.53 μM^[1]. It is used in research on obesity and cancer to explore the connection between fatty acid synthesis, energy metabolism, tumor growth, and survival. C75 is also an effective activator of CPT1A^[2].

In vitro, it inhibits PC3 cell growth with a 24-hour IC₅₀ of 35μM and reduces the growth of LNCaP spheroids in a concentration-dependent manner with an IC₅₀ of 50μM^[3]. Additionally, C75-mediated CPT 1A activation inhibits EMT, as indicated by reduced migration and α-SMA expression in HK-2 cells^[4].

In vivo, C75 injection suppresses fasting-induced c-Fos expression in specific hypothalamic nuclei and reduces mouse feeding by ≥ 95% within 2 hours at a dose of 30 mg/kg^[5]. In DIO mice, C75 treatment led to a 50% weight loss and a 32.9% increase in energy production due to fatty acid oxidation^[2].

References:

[1] Wang X , Lin J , Chen Y ,et al.Novel fatty acid synthase (FAS) inhibitors: Design, synthesis, biological evaluation, and molecular docking studies[J].Bioorganic & Medicinal Chemistry, 2009, 17(5):1898-1904.

[2] Thupari JN, et al. C75 increases peripheral energy utilization and fatty acid oxidation in diet-induced obesity. Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9498-502.

[3] Rae C, et al. Inhibition of Fatty Acid Synthase Sensitizes Prostate Cancer Cells to Radiotherapy. RADIATION RESEARCH 184, 482–493 (2015).

[4] L Peng, C Wang, S Yu, et al. Dysregulated lipid metabolism is associated with kidney allograft fibrosis. Lipids in Health and Disease, 2024(23).

[5] Gao S, et al. Effect of the anorectic fatty acid synthase inhibitor C75 on neuronal activity in the hypothalamus and brainstem. Proc Natl Acad Sci U S A. 2003 May 13;100(10):5628-33.