UK-5099 (Synonyms: PF-1005023;UK5099;UK 5099;PF1005023;PF 1005023) |
| Catalog No.GC11865 |
UK-5099 is a mitochondrial pyruvate carrier (MPC) inhibitor with an IC50 value of 50nM for inhibiting pyruvate-dependent O2 consumption.
Products are for research use only. Not for human use. We do not sell to patients.
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.
| 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 | |
| Synonyms | PF-1005023;UK5099;UK 5099;PF1005023;PF 1005023 | ||
| Chemical Name | (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 | ||
| Formula | C18H12N2O2 | M.Wt | 288.3 |
| Solubility | ≥ 28.8 mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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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- Purity: >99.50%
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