C75
目录号 : GC34065
C75 是一种脂肪酸合成酶 (FASN/FAS) 抑制剂，IC50为15.53 μM，在多种癌症模型中具有潜在的治疗作用。C75也是一种有效的CPT1A激活剂。
Cas No.:218137-86-1
Sample solution is provided at 25 µL, 10mM.
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- Purity: >99.50%
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Cell experiment [1]: |
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Cell lines |
HepG 2、SMMC 7721、Hep 3B cells |
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Preparation method |
Cells (5.0 x 106/10 cm dish) were treated with C75 for the indicated time intervals. Control cells received equivalent amounts of DMSO alone. FAS activity of cytoplasmic fractions of cells was measured by fluorescence quantification after exposure to 15 μg/ml C75 for 15 or 30 min. |
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Reaction Conditions |
15 μg/ml ; 15 or 30 min. |
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Applications |
Treatment of cells with C75 (15 μg/ml initial dose) produced significant reductions in FAS activity in HepG2 and Hep3B cells within 15 min, and in SMMC7721 cells within 30 min. |
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Animal experiment [2]: |
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Animal models |
Twelve-week-old DIO C57BL6J male mice |
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Preparation method |
DIO C57BL6J mice were fed a synthetic diet consisting of 60% calories from fat after weaning. Mice were maintained on a 12-h light-dark cycle at 25°C for 1 week before treatment. C75 and etomoxil were dissolved in RPMI medium 1640 and injected intraperitoneally at the indicated doses. Three mice were treated with C75 (20 mg/kg) on day 0. Subsequent doses were administered as follows: 15 mg/kg on day 2; 10 mg/kg on day 4; 15 mg/kg. On days 6 and 8, four mice received RPMI medium 1640. |
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Dosage form |
10-20 mg/kg; i.p. |
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Applications |
In DIO mice, C75 treatment led to a 50% weight loss and a 32.9% increase in energy production due to fatty acid oxidation |
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References: [1] Gao Y , Lin L P .Growth arrest induced by C75, A fatty acid synthase inhibitor, was partially modulated by p38 MAPK but not by p53 in human hepatocellular carcinoma.[J].Cancer Biology & Therapy, 2006, 5(8):978-985. [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. |
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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]。
| Cas No. | 218137-86-1 | SDF | |
| Canonical SMILES | O=C(C(C1=C)C(CCCCCCCC)OC1=O)O | ||
| 分子式 | C14H22O4 | 分子量 | 254.32 |
| 溶解度 | DMSO : ≥ 83.3 mg/mL (327.54 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.9321 mL | 19.6603 mL | 39.3205 mL |
| 5 mM | 0.7864 mL | 3.9321 mL | 7.8641 mL |
| 10 mM | 0.3932 mL | 1.966 mL | 3.9321 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Toll-like receptor mediated inflammation requires FASN-dependent MYD88 palmitoylation
Nat Chem Biol 2019 Sep;15(9):907-916.PMID:31427815DOI:10.1038/s41589-019-0344-0.
Toll-like receptor (TLR)/myeloid differentiation primary response protein (MYD88) signaling aggravates sepsis by impairing neutrophil migration to infection sites. However, the role of intracellular fatty acids in TLR/MYD88 signaling is unclear. Here, inhibition of fatty acid synthase by C75 improved neutrophil chemotaxis and increased the survival of mice with sepsis in cecal ligation puncture and lipopolysaccharide-induced septic shock models. C75 specifically blocked TLR/MYD88 signaling in neutrophils. Treatment with GSK2194069 that targets a different domain of fatty acid synthase, did not block TLR signaling or MYD88 palmitoylation. De novo fatty acid synthesis and CD36-mediated exogenous fatty acid incorporation contributed to MYD88 palmitoylation. The binding of IRAK4 to the MYD88 intermediate domain and downstream signal activation required MYD88 palmitoylation at cysteine 113. MYD88 was palmitoylated by ZDHHC6, and ZDHHC6 knockdown decreased MYD88 palmitoylation and TLR/MYD88 activation upon lipopolysaccharide stimulus. Thus, intracellular saturated fatty acid-dependent palmitoylation of MYD88 by ZDHHC6 is a therapeutic target of sepsis.
The fatty acid synthase inhibitor C75 differentially affects the adipogenic differentiation of multipotent cells and preadipocytes
FEBS Lett 2022 Dec;596(24):3191-3202.PMID:35689495DOI:10.1002/1873-3468.14424.
Previously, we revealed the dual enhancing effect of netoglitazone, an agonist of the peroxisome proliferator-activated receptor γ, on adipogenesis and osteoblastogenesis, and reported that fatty acid synthase (FASN) knockdown selectively repressed its pro-adipogenic effect. Here, we examined if a FASN inhibitor, C75, could selectively repress the pro-adipogenic effect of netoglitazone. Surprisingly, C75 promoted the adipogenic differentiation of multipotent C3H10T1/2 cells but inhibited 3T3-L1 preadipocytes. By identifying glycogen synthase kinase-3β and intracellular cAMP levels as regulatory targets of C75, we ultimately found the differential expression of adenosine receptor 3 (AR3) and AR2a on these cells. Inhibition of AR3 on C3H10T1/2 and AR2a on 3T3-L1 inhibited the effects of C75 on the differentiation of these cells. Our findings imply that cell-type-specific AR expression might account for the differential adipogenic effects of C75.
C75 alters central and peripheral gene expression to reduce food intake and increase energy expenditure
Endocrinology 2005 Jan;146(1):486-93.PMID:15498887DOI:10.1210/en.2004-0976.
C75, a synthetic inhibitor of fatty acid synthase (FAS), causes anorexia and profound weight loss in lean and genetically obese mice. C75 also acts as a stimulator of carnitine palmitoyltransferase-1 to induce fatty acid oxidation. To approximate human obesity, we used a 2-wk C75 treatment model for diet-induced obese (DIO) mice to investigate the central and peripheral effects of C75 on gene expression. C75 treatment decreased food intake, increased energy expenditure, and reduced body weight more effectively in DIO than in lean mice. Analysis of the gene expression changes in hypothalamus demonstrated that the reduced food intake in C75-treated DIO mice might be mediated by inhibition of orexigenic neuropeptide expression and induction of anorexigenic neuropeptide expression. Gene expression changes in peripheral tissues indicated that C75 increased energy expenditure by the induction of genes involved in fatty acid oxidation. C75 also inhibited the expression of genes in peripheral tissues responsible for fatty acid synthesis and accumulation. The patterns of the changes in central and peripheral gene expression that occur with C75 treatment provide mechanisms to explain the reduced food intake and increased energy expenditure observed with C75.
C75, a fatty acid synthase inhibitor, modulates AMP-activated protein kinase to alter neuronal energy metabolism
J Biol Chem 2004 Jan 30;279(5):3817-27.PMID:14615481DOI:10.1074/jbc.M310991200.
C75, a synthetic inhibitor of fatty acid synthase (FAS), is hypothesized to alter the metabolism of neurons in the hypothalamus that regulate feeding behavior to contribute to the decreased food intake and profound weight loss seen with C75 treatment. In the present study, we characterize the suitability of primary cultures of cortical neurons for studies designed to investigate the consequences of C75 treatment and the alteration of fatty acid metabolism in neurons. We demonstrate that in primary cortical neurons, C75 inhibits FAS activity and stimulates carnitine palmitoyltransferase-1 (CPT-1), consistent with its effects in peripheral tissues. C75 alters neuronal ATP levels and AMP-activated protein kinase (AMPK) activity. Neuronal ATP levels are affected in a biphasic manner with C75 treatment, decreasing initially, followed by a prolonged increase above control levels. Cerulenin, a FAS inhibitor, causes a similar biphasic change in ATP levels, although levels do not exceed control. C75 and cerulenin modulate AMPK phosphorylation and activity. TOFA, an inhibitor of acetyl-CoA carboxylase, increases ATP levels, but does not affect AMPK activity. Several downstream pathways are affected by C75 treatment, including glucose metabolism and acetyl-CoA carboxylase (ACC) phosphorylation. These data demonstrate that C75 modulates the levels of energy intermediates, thus, affecting the energy sensor AMPK. Similar effects in hypothalamic neurons could form the basis for the effects of C75 on feeding behavior.
Anorexigenic C75 alters c-Fos in mouse hypothalamic and hindbrain subnuclei
Neuroreport 2004 Apr 9;15(5):925-9.PMID:15073544DOI:10.1097/00001756-200404090-00038.
The fatty acid synthase inhibitor C75 reduces feeding rapidly and for several days. We investigated brain sites potentially involved in actions of i.p. C75 in mice by examining c-Fos. At 3 h C75 increased numbers of c-Fos-immunoreactive cells in hindbrain feeding-related nuclei, and in the paraventricular nucleus (PVN), lateral aspects of the arcuate nucleus (ARC), and in the central amygdala. At 24 h C75 prevented fasting-induced c-Fos expression in the medial ARC and three of its targets: lateral magnocellular PVN, lateral hypothalamus, and dorsomedial hypothalamus. C75, but not fasting, increased c-Fos in parvocellular PVN. This pattern of results suggests a shift from hindbrain-initiated short-term actions to activation of hypothalamic mechanisms that could mediate the long-term anorectic responses to C75.