trans-C75

trans-C75 ((±)-C75) is an enantiomer of C75. C75 is a synthetic fatty-acid synthase (FASN) inhibitor.

In Vitro, trans-C75 ((±)-C75) inhibits PC3 cell growht with an IC₅₀ of 35 μM at 24 h.
trans-C75 ((±)-C75)(10-50 μM) also reduces the growth of LNCaP spheroids in a concentration-dependent manner with an IC₅₀ of 50 μM^[1].
trans-C75 ((±)-C75) inhibits FAS activity and has a cytotoxic effect on tumor cell lines, without affecting food consumption.
trans-C75 ((±)-C75) inhibits CPT1 and its administration produces anorexia, suggesting that central inhibition of CPT1 is essential for the anorectic effect of C75. The differential activity of C75 enantiomers may lead to the development of potential new specific drugs for cancer and obesity^[2].

In Vivo,C75 blocks fasting-induced c-Fos expression in the arcuate nucleus (Arc), lateral hypothalamic area (LHA), and paraventricular nucleus (PVN) 10–24 h after i.p. injection. Intraperitoneal administration of C75 at 30 mg/kg body weight inhibits food intake of mice by ≥95% within 2 h after i.p. injection^[3].
C75-treated DIO mice has a 50% greater weight loss, and a 32.9% increased production of energy because of fatty acid oxidation. C75 treatment of rodent adipocytes and hepatocytes and human breast cancer cells increases fatty acid oxidation and ATP levels by increasing CPT-1 activity, even in the presence of elevated concentrations of malonyl-CoA^[4].

References:
[1]. Rae C, et al. Inhibition of Fatty Acid Synthase Sensitizes Prostate Cancer Cells to Radiotherapy.
[2]. Makowski K, et al. Differential pharmacologic properties of the two C75 enantiomers: (+)-C75 is a strong anorectic drug; (-)-C75 has antitumor activity. Chirality. 2013 May;25(5):281-7.
[3]. 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.
[4]. 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.

trans-C75 ((±)-C75) 是 C75 的对映异构体，C75 是脂肪酸合成酶 (FASN) 的抑制剂。

在体外，trans-C75 ((±)-C75) 抑制 PC3 细胞生长，24 小时的 IC₅₀ 为 35 μM。
trans-C75 ((±)-C75) (10-50 μM) 还以浓度依赖性方式减少 LNCaP 球体的生长，IC₅₀ 为 50 μM^[1]。
trans-C75 ((±)-C75) 抑制FAS活性，对肿瘤细胞系有细胞毒作用，不影响进食。
trans-C75 ((±)-C75) 抑制CPT1，其给药产生厌食，提示中枢抑制CPT1对 C75 的厌食作用至关重要。C75 对映异构体的不同活性可能会导致开发潜在的新的癌症和肥胖特异性药物^[2]。

在体内，腹腔注射后 10-24 小时，C75 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 的 C75 后 2 小时内抑制小鼠摄食 ≥ 95%^[3]。
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%。C75 处理啮齿动物脂肪细胞和肝细胞以及人类乳腺癌细胞可通过增加 CPT-1 活性来增加脂肪酸氧化和 ATP 水平，即使存在升高浓度的丙二酰辅酶 A 也是如此^[4]。