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.
C75是脂肪酸合成酶(FASN/FAS)的特异性抑制剂，C75显示出中等的FAS抑制活性，IC50为15.53 μM[1]。C75通常用于肥胖和癌症的研究，尤其是在探讨脂肪酸合成与能量代谢、肿瘤生长和存活之间的联系。C75也是一种有效的CPT1A激活剂[2]。
在体外，C75抑制PC3细胞生长，24h的IC50为35μM。C75 (10-50 μM) 还以浓度依赖性方式减少LNCaP球状体的生长，IC50为50μM[3]。此外，C75介导的CPT 1A激活可有效抑制EMT，表现为HK-2细胞迁移和α-SMA表达的减少[4]。
在体内，C75腹腔注射后10-24小时，阻断空腹诱导的弓状核(Arc)、下丘脑外侧区(LHA)和室旁核(PVN)中的c-Fos表达。腹膜内注射 30 mg/kg 体重的 C75 后2小时内可抑制小鼠摄食≥ 95%[5]。由于脂肪酸氧化，C75处理的DIO小鼠体重减轻了50%，能量产生增加了32.9% [2]。