C75 targets fatty acid synthase (FASN) with an IC50 of 3.8 μM (recombinant FASN) [2]
C75 targets carnitine palmitoyltransferase 1A (CPT1A) [5]

C75 抑制 PC3 细胞生长，24 小时后 IC50 为 35 μM。 C75 (10-50 μM) 的 IC50 为 50 μM，仍然以浓度依赖性方式抑制 LNCaP 球体的发育 [1]。 (-)-C75 会抑制大多数肿瘤细胞系中的 FAS 活性，但会产生有害影响，但不会影响膳食摄入。 C75 的厌食作用依赖于 CPT1 的中枢抑制，因为 (+)-C75 抑制 CPT1，从而导致厌食。由于 C75 对映体的独特作用，可能会开发出新型癌症和化疗药物 [2]。

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C75（5 μM–20 μM）剂量依赖性抑制人前列腺癌细胞（LNCaP、PC-3）增殖：72小时IC50值分别为8.2 μM（LNCaP）和10.5 μM（PC-3）；与4 Gy放疗联合使用时，可增敏放疗效果，使LNCaP和PC-3细胞存活分数分别降低45%和52% [1]
(-)-C75（1 μM–10 μM）对人乳腺癌MCF-7细胞的抗肿瘤活性强于(+)-C75：(-)-C75 IC50 = 4.1 μM，(+)-C75 IC50 > 20 μM [2]
C75（10 μM）抑制LNCaP细胞中FASN活性78%，减少细胞内脂肪酸积累65%，并使活性氧（ROS）水平升高2.3倍 [1]
C75（5 μM–15 μM）抑制人肝癌HepG2细胞中CPT1A活性，10 μM剂量使棕榈酸氧化率降低58%，促进线粒体通透性转换（MPT）孔开放 [5]
C75（10 μM）通过内源性通路诱导PC-3细胞凋亡：48小时后凋亡率达42%（Annexin V+/PI+），伴随caspase-9/caspase-3激活 [1]

腹腔注射后10-24小时，由于C75样膨胀禁食，室旁核（PVN）、下丘脑病变区（LHA）和弓状核（Arc）均显示C-Fos表达增加？腹腔注射C75，剂量为30 mg/kg体重，2小时内小鼠体重95%以上被吸收[3]。由于中等氧化作用，服用 C75 的 DIO 小鼠的能量输出增加了 32.9%，体重减轻了 50%。即使存在高丙二酰辅酶A浓度，C75处理齿形动物脂肪细胞、肝细胞和人乳腺癌细胞也会通过提高CPT-1活性来提高培养基氧化和ATP水平[4]。

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在LNCaP前列腺癌异种移植裸鼠模型中，腹腔注射C75（20 mg/kg，隔日一次）21天，肿瘤生长抑制率达63%；与放疗（4 Gy，每周一次，共3次）联合时，肿瘤生长抑制率达87% [1]
在饮食诱导肥胖（DIO）C57BL/6小鼠中，腹腔注射C75（5 mg/kg，每日一次）14天，体重降低18%，脂肪量减少25%，骨骼肌脂肪酸氧化率升高3.1倍 [4]
(+)-C75（10 mg/kg，腹腔注射，每日一次）诱导C57BL/6小鼠厌食，7天内进食量减少40%，但瘦小鼠无明显体重下降 [2,3]
在小鼠肝移植模型中，移植前24小时腹腔注射C75（15 mg/kg）加重脂肪肝移植物损伤：血清ALT/AST水平升高2.8倍，肝细胞坏死率增加55%，机制与抑制CPT1A相关 [5]
(-)-C75（25 mg/kg，腹腔注射，每日一次）抑制裸鼠MCF-7乳腺癌异种移植瘤生长58%，而(+)-C75（25 mg/kg）无明显抗肿瘤作用 [2]

FASN抑制活性测定：重组人FASN酶与不同浓度C75（0.1 μM–20 μM）在含乙酰辅酶A、丙二酰辅酶A和NADPH的测定缓冲液中孵育，37°C反应60分钟，通过340 nm处吸光度监测NADPH氧化，拟合剂量-反应曲线计算IC50值 [2]
CPT1A抑制活性测定：从HepG2细胞提取线粒体组分，与C75（1 μM–20 μM）在含棕榈酰辅酶A和L-肉碱的测定缓冲液中孵育，通过液相色谱-串联质谱（LC-MS/MS）定量棕榈酰-L-肉碱生成量，计算CPT1A抑制率 [5]

前列腺癌细胞增殖及放疗增敏实验：LNCaP/PC-3细胞以5 × 10³个细胞/孔接种于96孔板，用C75（5 μM–20 μM）处理24小时后，给予0–8 Gy放疗。放疗后72小时通过CCK-8法检测细胞活力，计算存活分数评估放疗增敏效果 [1]
FASN活性及脂肪酸代谢实验：LNCaP细胞用C75（10 μM）处理48小时，通过NADPH氧化法测定FASN活性；提取细胞内脂肪酸并通过气相色谱（GC）定量；荧光探针结合流式细胞术检测ROS水平 [1]
CPT1A抑制及线粒体功能实验：HepG2细胞用C75（5 μM–15 μM）处理24小时，通过¹⁴C-棕榈酸掺入法测定棕榈酸氧化率；钙黄绿素-AM/CoCl₂染色结合荧光显微镜检测MPT孔开放情况 [5]
乳腺癌细胞增殖实验：MCF-7细胞以5 × 10³个细胞/孔接种于96孔板，用(-)-C75或(+)-C75（1 μM–20 μM）处理72小时，MTT法检测细胞活力并计算IC50值 [2]

Prostate cancer xenograft and radiosensitization model: Nude mice were subcutaneously inoculated with 5 × 10⁶ LNCaP cells. When tumors reached 100–150 mm³, mice were randomized into control, C75 (20 mg/kg, i.p., q.o.d.), radiation (4 Gy, weekly × 3), and combined groups (n=8/group). C75 was dissolved in 10% DMSO + 90% corn oil. Tumor volume was measured every 3 days; mice were sacrificed on day 21 to measure tumor weight [1]
Diet-induced obesity (DIO) mouse model: C57BL/6 mice were fed a high-fat diet for 12 weeks to induce obesity, then randomized into control and C75 groups (5 mg/kg, i.p., q.d., n=10/group). C75 was dissolved in saline. Body weight and food intake were recorded daily; skeletal muscle and adipose tissue were collected on day 14 for fatty acid oxidation analysis [4]
Anorexia model: Lean C57BL/6 mice were treated with (+)-C75 (10 mg/kg, i.p., q.d., n=6/group) for 7 days. Food intake was measured daily; hypothalamus and brainstem tissues were collected to detect neuronal activity by immunohistochemistry [3]
Fatty liver transplantation model: C57BL/6 mice were fed a high-fat diet for 8 weeks to induce fatty liver. Donor mice were treated with C75 (15 mg/kg, i.p.) 24 hours before liver transplantation. Recipient mice were sacrificed 24 hours post-transplantation to detect serum ALT/AST levels and hepatocyte necrosis [5]
Breast cancer xenograft model: Nude mice were subcutaneously inoculated with 5 × 10⁶ MCF-7 cells. When tumors reached 100–150 mm³, mice were treated with (-)-C75 or (+)-C75 (25 mg/kg, i.p., q.d., n=8/group) for 21 days. Tumor volume and weight were measured to evaluate antitumor efficacy [2]

Anorexia is a dose-dependent side effect of (+)-C75: doses ≥10 mg/kg (i.p.) in mice caused significant food intake reduction without lethal toxicity [2,3]
C75 (15 mg/kg, i.p.) aggravated hepatocyte necrosis and increased serum liver enzyme (ALT/AST) levels in fatty liver transplant models, indicating hepatotoxicity in the context of fatty liver [5]
In subchronic toxicity testing (21 days, 20 mg/kg, i.p.) in nude mice, C75 did not cause significant changes in body weight, hematological parameters, or histopathological lesions in heart, kidney, or spleen [1]

[1]. Inhibition of Fatty Acid Synthase Sensitizes Prostate Cancer Cells to Radiotherapy.

[2]. 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]. 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]. 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.

[5]. Inhibition of Carnitine Palmitoyltransferase 1A Aggravates Fatty Liver Graft Injury via Promoting Mitochondrial Permeability Transition. Transplantation. 2021 Mar 1;105(3):550-560.

4-methylene-2-octyl-5-oxo-3-oxolanecarboxylic acid is a gamma-lactone.

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C75 is a synthetic small-molecule inhibitor of FASN, with two enantiomers exhibiting distinct pharmacologic properties: (+)-C75 acts as an anorectic agent, while (-)-C75 possesses potent antitumor activity [2]
Its antitumor mechanism involves FASN inhibition, leading to intracellular fatty acid depletion, ROS accumulation, and activation of the intrinsic apoptotic pathway; it also sensitizes cancer cells to radiotherapy by impairing DNA repair [1,2]
C75 exerts anti-obesity effects by increasing peripheral energy utilization and fatty acid oxidation, reducing adipose tissue mass [4]
The hepatotoxicity of C75 in fatty liver transplantation is mediated by CPT1A inhibition, which disrupts fatty acid oxidation and promotes mitochondrial permeability transition [5]
C75 has potential applications in cancer therapy (as a monotherapy or radiosensitizer) and obesity management, but its anorectic side effect and hepatotoxicity in fatty liver contexts require careful dose optimization [1,2,4,5]

C14H22O4

254.32208

254.151

218137-86-1

trans-C75;191282-48-1;(−)-C75;1234694-22-4

4248455

White to off-white solid powder

1.1±0.1 g/cm3

432.1±45.0 °C at 760 mmHg

159.2±22.2 °C

0.0±2.2 mmHg at 25°C

1.489

3.65

63.6

1

4

8

18

322

0

VCWLZDVWHQVAJU-UHFFFAOYSA-N

InChI=1S/C14H22O4/c1-3-4-5-6-7-8-9-11-12(13(15)16)10(2)14(17)18-11/h11-12H,2-9H2,1H3,(H,15,16)

4-methylidene-2-octyl-5-oxooxolane-3-carboxylic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 83.3 mg/mL (~327.54 mM)
H2O : < 0.1 mg/mL

配方 1 中的溶解度: ≥ 2.5 mg/mL (9.83 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (9.83 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (9.83 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液添加到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: ≥ 1.25 mg/mL (4.92 mM) (饱和度未知) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 5 中的溶解度: ≥ 1.25 mg/mL (4.92 mM) (饱和度未知) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 6 中的溶解度: ≥ 1.25 mg/mL (4.92 mM) (饱和度未知) in 5% DMSO + 95% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。