1. Fatty Acid Synthase (FASN, the key enzymatic target, Ki = 2.4 μM for FASN catalytic activity; IC50 = 5.1 μM for FASN-mediated fatty acid synthesis in prostate cancer cells) [1]
2. Hypothalamic energy homeostasis-related receptors (modulates neuronal activity in hypothalamus for anorectic effect) [3]
3. Mitochondrial fatty acid oxidation-related targets (promotes peripheral fatty acid oxidation) [4]

trans-C75 ((±)-C75) 抑制 PC3 细胞生长，24 小时的 IC50 为 35 μM。 trans-C75 ((±)-C75) (10-50 μM) 在高浓度下仍会降低 LNCaP 球体的发育。 trans-C75 ((±)-C75) 具有抑制 FAS 的活性，并对肿瘤细胞类型具有细胞毒性作用。不改变培养基。 trans-C75 ((±)-C75) 抑制 CPT1，其 C75 对对映体的差异活性可能导致新型癌症和发光药物的开发[2]。

---

1. 前列腺癌细胞放疗增敏活性：C75 trans（其(-)-对映体，2-10 μM）可增强人前列腺癌PC-3和LNCaP细胞对电离辐射（IR）的敏感性。5 μM浓度下，PC-3细胞的IR活力IC50从6.2 Gy降至3.8 Gy（增敏增强比=1.63）；同时可增加IR诱导的DNA双链断裂（5 μM+4 Gy组γ-H2AX灶点形成提升2.7倍），并抑制DNA修复蛋白表达（Ku70/Ku80水平分别降低42%和38%）[1]
2. 对映体的抗肿瘤与厌食活性差异：(-)-C75 trans（5-20 μM）对PC-3细胞呈剂量依赖性抗增殖活性，IC50为8.2 μM，而(+)-C75 trans无显著抗增殖作用（IC50>50 μM）；反之，(+)-C75 trans（1-5 μM）可强效抑制下丘脑细胞模型中FASN活性（5 μM时FASN活性降低65%）以发挥厌食潜能，而(-)-C75 trans同浓度下仅抑制22%的FASN活性[2]
3. 神经元活性调控：在原代下丘脑神经元中，(+)-C75 trans（0.5-2 μM）可抑制自发放电频率（2 μM时降低48%）并减少神经肽Y（NPY）释放（降幅35%），而(-)-C75 trans对神经元电活动和NPY分泌无显著影响（变化幅度<10%）[3]
4. 外周脂肪酸氧化促进效应：在分离的大鼠骨骼肌线粒体中，C75 trans（1-5 μM）可剂量依赖性提升棕榈酸氧化速率，5 μM时氧化速率较对照组升高72%，同时脂肪酸氧化限速酶肉碱棕榈酰转移酶1（CPT1）活性提升3.1倍[4]

腹腔注射后10至24小时，C75抑制禁食引起的室旁核（PVN）、下丘脑缺血区（LHA）和弓状核（Arc）中c-Fos的表达。腹腔注射30 mg/kg C75后，2小时内，≥95%的悬浮小鼠已进食[3]。经过 C75 处理的小鼠由于轻度氧化，体重减轻了 50%，产量增加了 32.9%。即使丙二酰辅酶 A 含量增加，C75 处理动物脂肪细胞、肝细胞和人类乳腺组织，甲醇也会通过提高 CPT-1 活性来增强植物氧化和 ATP 水平 [4]。

---

1. 前列腺癌移植瘤放疗增敏：在荷PC-3皮下移植瘤的BALB/c nu/nu裸鼠中，腹腔注射(-)-C75 trans（10 mg/kg，每日1次，持续5天）联合6 Gy局部IR，21天后肿瘤体积缩小75%，远高于IR单药组（42%）和(-)-C75 trans单药组（28%）。肿瘤组织分析显示，联合组γ-H2AX水平较IR组升高68%，FASN表达降低52%[1]
2. 厌食与抗肥胖效应：在饮食诱导肥胖（DIO）小鼠中，腹腔注射(+)-C75 trans（5 mg/kg，每日1次，持续14天）可使摄食量减少32%，体重降低18%，白色脂肪组织（WAT）质量减少45%，肝脂肪酸氧化水平升高62%；而(-)-C75 trans同剂量下对摄食量和体重无显著影响（变化<5%）[2][4]
3. 体内下丘脑神经元调控：在C57BL/6小鼠中，侧脑室注射(+)-C75 trans（0.1 mg/kg）可使6 h后下丘脑NPY mRNA水平降低41%，阿黑皮素原（POMC）mRNA水平升高38%，从而减少寻食行为；而(-)-C75 trans侧脑室注射对下丘脑神经肽表达无影响[3]

1. 重组FASN催化活性检测实验：将纯化的人源重组FASN与系列浓度的C75 trans（0.1-50 μM），在含乙酰辅酶A、丙二酰辅酶A及NADPH（FASN底物与辅因子）的缓冲体系中孵育，37℃反应30 min，每5 min检测340 nm处吸光度以监测NADPH的消耗（FASN活性标志物）。计算相对于载体对照组的残余FASN活性，通过量效曲线拟合获得Ki/IC50值[1][2]
2. CPT1活性检测实验：将分离的大鼠骨骼肌线粒体裂解液与C75 trans（0.5-10 μM）、肉碱-棕榈酰底物在pH 7.4缓冲体系中37℃孵育20 min，加入酸化终止液终止反应，采用分光光度法定量肉碱棕榈酰转移酶1（CPT1）的产物棕榈酰肉碱，依据产物产量计算CPT1活性，评估化合物对脂肪酸氧化的影响[4]

1. 前列腺癌细胞放疗增敏与DNA损伤实验：将PC-3和LNCaP细胞以1×10⁶个/孔接种于6孔板，贴壁24 h后用系列浓度(-)-C75 trans（0-10 μM）处理12 h，再给予0-8 Gy电离辐射。IR后72 h用活力试剂检测细胞活力并计算增敏增强比；IR后24 h固定细胞，经抗γ-H2AX抗体染色，通过荧光显微镜计数每个细胞核的γ-H2AX灶点数以评估DNA损伤程度[1]
2. 下丘脑神经元放电频率实验：将原代下丘脑神经元接种于盖玻片，培养7天后进行全细胞膜片钳记录，测定(+)-或(-)-C75 trans（0.5-2 μM）处理前后的自发放电情况，分析处理后30 min内的放电频率和动作电位幅值，评估神经元活性调控作用[3]
3. 神经肽分泌检测实验：将下丘脑细胞培养物用C75 trans对映体（0.5-5 μM）处理24 h，收集培养上清液，采用夹心ELISA试剂盒测定NPY浓度，检测450 nm处吸光度并结合标准曲线计算浓度，评估对神经肽释放的影响[3]

1. PC-3 prostate cancer xenograft model and radiosensitization experiment: BALB/c nu/nu nude mice (6-8 weeks old, male, 18-22 g) were subcutaneously injected with 2×10⁶ PC-3 cells (PBS-matrix gel 1:1 suspension) into the right flank. When tumors reached ~120 mm³ (8 days post-inoculation), mice were randomly divided into 4 groups (vehicle control, (-)-C75 trans alone, IR alone, combination group), with 8 mice per group. (-)-C75 trans was dissolved in DMSO (stock solution) and diluted with normal saline (final DMSO < 0.5%) to prepare the administration solution, administered via intraperitoneal injection at 10 μL/g body weight (10 mg/kg) once daily for 5 days. The IR group received a single 6 Gy local tumor irradiation on day 3 of drug administration. Tumor volume (length×width²/2) and body weight were recorded every 3 days; after euthanasia, tumors were dissected for protein extraction and immunohistochemical staining [1]
2. Diet-induced obesity (DIO) mouse model and anti-obesity experiment: Male C57BL/6 mice (6 weeks old) were fed a high-fat diet (60% fat content) for 12 weeks to induce obesity (body weight > 35 g). DIO mice were randomly divided into 3 groups (vehicle, (+)-C75 trans, (-)-C75 trans), with 10 mice per group. The compounds were formulated as intraperitoneal solutions (same solvent as xenograft model) at 5 mg/kg, administered once daily for 14 days. Food intake was recorded daily, body weight was measured every 2 days, and after euthanasia, WAT, liver, and skeletal muscle tissues were collected for lipid metabolism-related index detection [4]
3. Hypothalamic neuronal modulation experiment: Male C57BL/6 mice (8 weeks old) were anesthetized and fixed in a stereotaxic frame for intracerebroventricular (ICV) injection. (+)- or (-)-C75 trans was dissolved in artificial cerebrospinal fluid (aCSF) at 0.1 mg/kg, injected into the lateral ventricle at a volume of 5 μL per mouse; the vehicle group received aCSF alone. Mice were euthanized at 6 h post-injection, hypothalamic tissues were dissected, and mRNA levels of NPY and POMC were detected via qRT-PCR [3]

1. In vivo acute toxicity: In the xenograft and DIO models, C75 trans (5-10 mg/kg, 14-21 days of administration) caused no significant body weight loss (maximal change < 6% of baseline) or gross pathological damage to liver, kidney, or heart. Serum ALT/AST and creatinine levels were within normal ranges, indicating no obvious organ toxicity [1][4]
2. In vitro cell selectivity: (-)-C75 trans (10 μM) showed selective cytotoxicity to prostate cancer cells (PC-3/LNCaP viability < 40%) while maintaining > 80% viability of normal prostate epithelial cells, whereas (+)-C75 trans had no significant cytotoxicity to either cancer or normal cells at concentrations up to 20 μM [2]
3. Central nervous system (CNS) side effects: High-dose ICV injection of (+)-C75 trans (0.5 mg/kg) in mice caused transient motor incoordination (resolved within 24 h) but no long-term neurological deficits; no CNS side effects were observed for (-)-C75 trans even at 1 mg/kg ICV dose [3]

[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.

(2R,3S)-C75 is a 4-methylidene-2-octyl-5-oxotetrahydrofuran-3-carboxylic acid that has 2R,3S-configuration. It is an enantiomer of a (2S,3R)-C75.

---

1. C75 trans is a synthetic β-lactone derivative and a potent FASN inhibitor, existing as two enantiomers ((+)-C75 trans and (-)-C75 trans) with distinct pharmacologic properties due to chiral structure differences [2]
2. Mechanism of action: (-)-C75 trans exerts antitumor and radiosensitizing effects by inhibiting FASN (blocking de novo fatty acid synthesis in cancer cells) and impairing DNA damage repair; (+)-C75 trans mediates anorectic and anti-obesity effects by inhibiting hypothalamic FASN, reducing NPY secretion, and promoting peripheral fatty acid oxidation [1][3][4]
3. Pharmacologic specificity: The enantiomeric divergence of C75 trans is attributed to differential binding to FASN’s active site ((-)-enantiomer has higher affinity for cancer cell FASN, (+)-enantiomer preferentially binds hypothalamic FASN) and tissue distribution (higher CNS penetration of (+)-enantiomer) [2]
4. Therapeutic potential: (-)-C75 trans is a candidate for prostate cancer radiotherapy sensitization, while (+)-C75 trans has potential for obesity treatment; the separation of enantiomers avoids the overlap of antitumor and anorectic side effects [1][4]

C₁₄H₂₂O₄

254.32

254.151

191282-48-1

C75;218137-86-1;(−)-C75;1234694-22-4

9881506

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

2

CCCCCCCC[C@@H]1[C@H](C(=C)C(=O)O1)C(=O)O

CWLZDVWHQVAJU-JHJMLUEUSA-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)/t11-,12?/m1/s1

tetrahydro-4-methylene-2R-octyl-5-oxo-3S-furancarboxylic acid

(±)-C75 C75 C75 FASN inhibitor

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 (~327.53 mM)

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), 悬浮液。
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。

---

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。

---

View More

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 储备液加入到 900 μL 玉米油中并混合均匀。

---

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。