AR-C155858
(Synonyms: (S)-6-[(3,5-二甲基-1H-吡唑-4-基)甲基]-5-[(4-羟基异唑烷-2-基)羰基]-1-异丁基-3-甲基噻吩并[2,3-D]嘧啶-2,4(1H,3H)-二酮,AR C155858) 目录号 : GC10680
AR-C155858是一种强效的单羧酸转运蛋白1（MCT1）抑制剂，Ki值为2.3nM，也能抑制MCT2，Ki值>10nM。
Cas No.:496791-37-8
Sample solution is provided at 25 µL, 10mM.
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AR-C155858 is a potent inhibitor of monocarboxylate transporter 1 (MCT1) with a Ki value of 2.3nM, and also inhibits MCT2 with a Ki value of >10nM[1]. AR-C155858 has potential immunomodulatory and chemotherapeutic properties[2, 3]. MCT1 is expressed in most tissues and promotes lactate uptake for oxidation in cardiac and red skeletal muscle, as well as gluconeogenesis in the liver and kidney of some species[4]. AR-C155858 can inhibit the proliferation, migration, spheroid formation and in vivo tumor growth of TAMR-MCF-7 cells[5].
In vitro, treatment of 4T1 breast cancer cells with AR-C155858 (0-500nM) for 48h inhibited cell growth in a concentration-dependent manner with an IC50 value of 20.3nM, inhibiting cellular L-lactate uptake[6].
In vivo, AR-C155858 (5mg/kg) administered intravenously to rats co-administered with γ-hydroxybutyrate (GHB) and ethanol significantly reduced the respiratory depressant and sedative effects of the drug-drug interaction (DDI) of GHB and ethanol co-administration, and reduced the brain concentration and brain-to-plasma concentration ratio of GHB[7].
References:
[1] Guan X, Rodriguez-Cruz V, Morris M E. Cellular uptake of MCT1 inhibitors AR-C155858 and AZD3965 and their effects on MCT-mediated transport of L-lactate in murine 4T1 breast tumor cancer cells[J]. The AAPS journal, 2019, 21: 1-10.
[2] Wang Z H, Peng W B, Zhang P, et al. Lactate in the tumour microenvironment: From immune modulation to therapy[J]. EBioMedicine, 2021, 73.
[3] Wang H, Zhou F, Qin W, et al. Metabolic regulation of myeloid-derived suppressor cells in tumor immune microenvironment: targets and therapeutic strategies[J]. Theranostics, 2025, 15(6): 2159.
[4] Ovens M J, Davies A J, Wilson M C, et al. AR-C155858 is a potent inhibitor of monocarboxylate transporters MCT1 and MCT2 that binds to an intracellular site involving transmembrane helices 7–10[J]. Biochemical Journal, 2010, 425(3): 523-530.
[5] Choi M C, Kim S K, Choi Y J, et al. Role of monocarboxylate transporter I/lactate dehydrogenase B-mediated lactate recycling in tamoxifen-resistant breast cancer cells[J]. Archives of Pharmacal Research, 2023, 46(11): 907-923.
[6] Guan X, Bryniarski M A, Morris M E. In vitro and in vivo efficacy of the monocarboxylate transporter 1 inhibitor AR-C155858 in the murine 4T1 breast cancer tumor model[J]. The AAPS journal, 2018, 21(1): 3.
[7] Rodriguez-Cruz V, Morris M E. γ-Hydroxybutyric Acid–Ethanol Drug-Drug Interaction: Reversal of Toxicity with Monocarboxylate Transporter 1 Inhibitors[J]. The Journal of Pharmacology and Experimental Therapeutics, 2021, 378(1): 42-50.
AR-C155858是一种强效的单羧酸转运蛋白1（MCT1）抑制剂，Ki值为2.3nM，也能抑制MCT2，Ki值>10nM[1]。AR-C155858具有潜在的免疫调节和化疗特性[2, 3]。MCT1在大多数组织中表达，并促进乳酸摄取，以便在心脏和红色骨骼肌中氧化，以及在某些物种的肝脏和肾脏中发生糖异生[4]。AR-C155858能够抑制TAMR-MCF-7细胞的增殖、迁移、球状体形成和体内肿瘤生长[5]。
在体外，AR-C155858（0-500nM）处理4T1乳腺癌细胞48h，以浓度依赖性方式抑制了细胞生长，IC50值为20.3nM，抑制了细胞L-乳酸摄取[6]。
在体内，AR-C155858（5mg/kg）通过静脉注射治疗γ-羟基丁酸（GHB）和乙醇共同给药处理的大鼠，显著降低了GHB和乙醇共同给药对该药物相互作用（DDI）的呼吸抑制和镇静的影响，并降低了GHB的脑浓度和脑与血浆浓度比[7]。
| Cell experiment [1]: | |
Cell lines | 4T1 cells |
Preparation Method | 4T1 cells were plated in 96-well plates at a cell density of 5.0×103 cells per well in 100μL of complete medium and allowed to adhere overnight. On the day of the study, the medium was removed and cells were washed with PBS. Cells were treated with 0-500nM AR-C155858 in 100μL of serum free medium for 48h. Relative cell growth was quantified using Cell Proliferation Reagent WST-1. The results were normalized to the vehicle control (< 0.1% DMSO) and expressed as percentage of cell growth. |
Reaction Conditions | 0-500nM; 48h |
Applications | AR-C155858 exhibited a concentration-dependent inhibitory effect on cell growth with an IC50 value of 20.3nM. |
References: | |
| Cas No. | 496791-37-8 | SDF | |
| 别名 | (S)-6-[(3,5-二甲基-1H-吡唑-4-基)甲基]-5-[(4-羟基异唑烷-2-基)羰基]-1-异丁基-3-甲基噻吩并[2,3-D]嘧啶-2,4(1H,3H)-二酮,AR C155858 | ||
| 化学名 | 6-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-5-[(4S)-4-hydroxy-1,2-oxazolidine-2-carbonyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione | ||
| Canonical SMILES | CC1=C(C(=NN1)C)CC2=C(C3=C(S2)N(C(=O)N(C3=O)C)CC(C)C)C(=O)N4CC(CO4)O | ||
| 分子式 | C21H27N5O5S | 分子量 | 461.53 |
| 溶解度 | DMSO: 100 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。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1667 mL | 10.8335 mL | 21.6671 mL |
| 5 mM | 0.4333 mL | 2.1667 mL | 4.3334 mL |
| 10 mM | 0.2167 mL | 1.0834 mL | 2.1667 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） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet