UK-5099
(Synonyms: PF-1005023;UK5099;UK 5099;PF1005023;PF 1005023) 目录号 : GC11865
UK-5099是一种线粒体丙酮酸载体（MPC）抑制剂，抑制丙酮酸依赖性O2消耗的IC50值为50nM。
Cas No.:56396-35-1
Sample solution is provided at 25 µL, 10mM.
UK-5099 is a mitochondrial pyruvate carrier (MPC) inhibitor with an IC50 value of 50nM for inhibiting pyruvate-dependent O2 consumption[1]. UK-5099 is an α-cyanocinnamate derivative that blocks pyruvate entry into mitochondria, impairs mitochondrial oxidative phosphorylation and triggers aerobic glycolysis[2]. UK-5099 can increase glutamate oxidation and prevent excitotoxic neuronal death[3].
In vitro, UK-5099 (25, 50µM) treatment of bone marrow-derived macrophages for 30min dose-dependently reduced the formation of the adaptor protein apoptosis-associated speck-like protein containing CARD (ASC)[4]. UK-5099 (40, 80µM) treatment of microglia significantly reduced the nuclear signal intensity of NF-κB and NF-IL6 in cells[5]. UK-5099 (10-150µM) treatment of 832/13 cells dose-dependently inhibited glucose-stimulated insulin secretion in cells[6].
In vivo, UK-5099 (3mg/kg) was intraperitoneally injected into mice bearing non-small cell lung cancer xenografts and synergized with syrosingopine to inhibit tumor growth[7].
References:
[1] Halestrap A P. The mitochondrial pyruvate carrier. Kinetics and specificity for substrates and inhibitors[J]. Biochemical Journal, 1975, 148(1): 85-96.
[2] Zeng Q, Si H, Lv K, et al. Determination and pharmacokinetics study of UK-5099 in mouse plasma by LC–MS/MS[J]. BMC Veterinary Research, 2022, 18(1): 145.
[3] Quansah E, Peelaerts W, Langston J W, et al. Targeting energy metabolism via the mitochondrial pyruvate carrier as a novel approach to attenuate neurodegeneration[J]. Molecular Neurodegeneration, 2018, 13: 1-12.
[4] Ran L, Chen M, Ye J, et al. UK5099 Inhibits the NLRP3 Inflammasome Independently of its Long‐Established Target Mitochondrial Pyruvate Carrier[J]. Advanced Science, 2024, 11(33): 2307224.
[5] Guimarães N C, Alves D S, Vilela W R, et al. Mitochondrial pyruvate carrier as a key regulator of fever and neuroinflammation[J]. Brain, Behavior, and Immunity, 2021, 92: 90-101.
[6] Patterson J N, Cousteils K, Lou J W, et al. Mitochondrial metabolism of pyruvate is essential for regulating glucose-stimulated insulin secretion[J]. Journal of Biological Chemistry, 2014, 289(19): 13335-13346.
[7] Li Y, Song Y, Shi Z, et al. Syrosingopine and UK5099 synergistically suppress non-small cell lung cancer by activating the integrated stress response[J]. Cell Death & Disease, 2024, 15(6): 431.
UK-5099是一种线粒体丙酮酸载体（MPC）抑制剂，抑制丙酮酸依赖性O2消耗的IC50值为50nM[1]。UK-5099是一种α-氰基肉桂酸酯衍生物，能够阻断丙酮酸进入线粒体，削弱线粒体氧化磷酸化并触发有氧糖酵解[2]。UK-5099能够增加谷氨酸氧化，防止兴奋性毒性神经元死亡[3]。
在体外，UK-5099（25, 50µM）处理骨髓来源的巨噬细胞30min，剂量依赖性地剂量依赖性地减少了衔接蛋白凋亡相关斑点样蛋白含有CARD（ASC）的形成[4]。UK-5099（40, 80µM）处理小胶质细胞，显著降低了细胞中NF-κB和NF-IL6的核信号强度[5]。UK-5099（10-150µM）处理832/13细胞，剂量依赖性地抑制了细胞中葡萄糖刺激的胰岛素分泌[6]。
在体内，UK-5099（3mg/kg）通过腹腔注射治疗非小细胞肺癌异种移植小鼠，与昔洛舍平协同抑制了肿瘤生长[7]。
| Cell experiment [1]: | |
Cell lines | Bone marrow-derived macrophages (BMDMs) |
Preparation Method | BMDMs isolated from ASC reporter mice (ASCcitrine BMDMs) were plated on chamber slides at 1×106/mL. Cells were primed the following day with LPS for 3h. After washing with PBS, cells were treated with 25µM or 50µM UK-5099 for 30min, followed by stimulation with nigericin for 1h. The cells were then washed with ice-cold PBS three times and fixed for 15min in fixation solution consisting of 4% PFA in PBS. After three times washing with PBST, nuclei were stained with DAPI. Images were captured using a laser-scanning confocal microscopy. |
Reaction Conditions | 25, 50µM; 30min |
Applications | ASC fluorescence was evenly distributed in resting macrophages, and the formation of dense specks was evident after stimulation with LPS plus nigericin. UK-5099 dose-dependently reduced the formation of ASC specks. |
| Animal experiment [2]: | |
Animal models | Balb/c nude mice |
Preparation Method | 5×106 PC-9 cells were subcutaneously inoculated into the Balb/c nude mice. Once the tumor volumes reached 50mm3, the mice were divided into four groups, each consisting of six mice: Control (PBS), Syrosingopine (7.5mg/kg), UK-5099 (3mg/kg), and a combination of Syrosingopine and UK-5099. Treatments, including Syrosingopine, UK-5099, or PBS, were administered to the mice through intraperitoneal injections continuously for 14 days. Throughout this period, observations were diligently made, recording the tumor volume and weight for subsequent analysis. |
Dosage form | 3mg/kg for 14 days; i.p. |
Applications | In vivo inhibition of tumor growth by the combination of Syrosingopine and UK-5099. |
References: | |
| Cas No. | 56396-35-1 | SDF | |
| 别名 | PF-1005023;UK5099;UK 5099;PF1005023;PF 1005023 | ||
| 化学名 | (E)-2-cyano-3-(1-phenylindol-3-yl)prop-2-enoic acid | ||
| Canonical SMILES | C1=CC=C(C=C1)N2C=C(C3=CC=CC=C32)C=C(C#N)C(=O)O | ||
| 分子式 | C18H12N2O2 | 分子量 | 288.3 |
| 溶解度 | ≥ 28.8 mg/mL in DMSO | 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。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.4686 mL | 17.343 mL | 34.6861 mL |
| 5 mM | 0.6937 mL | 3.4686 mL | 6.9372 mL |
| 10 mM | 0.3469 mL | 1.7343 mL | 3.4686 mL |
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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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计算结果:
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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2.
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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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