KMH-233
目录号 : GC61845
KMH-233 是一种有效，可逆的且选择性的 l 型氨基酸转运蛋白 1 (LAT1) 抑制剂，可抑制LAT1底物，l-leucin 的摄取 (IC50=18 µM) 以及细胞生长。即使在低浓度 (25 µM) 下，KMH-233 仍可显着增强 Bestatin 和顺铂的疗效。
Cas No.:1941174-13-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
KMH-233, a potent, reversible and selective l-type amino acid transporter 1 (LAT1) inhibitor, inhibits the uptake of LAT1 substrate, l-leucin (IC50=18 µM) as well as cell growth. KMH-233 significantly potentiates the efficacy of Bestatin and Cisplatin even at low concentrations (25 µM)[1].
KMH-233 is able to inhibit binding and transport of essential neutral amino acids and thus, inhibit the cell growth of cancer cells[1].KMH-233 shows a significant reduction of cell growth with an IC50 of 124 µM[1].KMH-233 is effective and able to potentiate the anti-proliferative efficacy of Bestatin (100 µM) and Cisplatin (100 µM) at a lower concentration of 25 µM, inhibiting cell growth 53% and 50%, respectively[1].
References:
[1]. Huttunen KM, et al. A Selective and Slowly Reversible Inhibitor of l-Type Amino Acid Transporter 1 (LAT1) Potentiates Antiproliferative Drug Efficacy in Cancer Cells. J Med Chem. 2016;59(12):5740-5751.
| Cas No. | 1941174-13-5 | SDF | |
| Canonical SMILES | O=C([C@H](CC1=CC=CC(C(NC2=C(C(C3=CC=C(C=C3)OCC(NC)=O)=C(C4=NC5=CC=CC=C5N24)C#N)C#N)=O)=C1)N)O | ||
| 分子式 | C32H25N7O5 | 分子量 | 587.58 |
| 溶解度 | DMSO : 100 mg/mL (170.19 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 | 1.7019 mL | 8.5095 mL | 17.019 mL |
| 5 mM | 0.3404 mL | 1.7019 mL | 3.4038 mL |
| 10 mM | 0.1702 mL | 0.8509 mL | 1.7019 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。
Hemocompatible LAT1-inhibitor can induce apoptosis in cancer cells without affecting brain amino acid homeostasis
Apoptosis 2020 Jun;25(5-6):426-440.PMID:32405891DOI:10.1007/s10495-020-01603-7.
Increased amounts of amino acids are essential for cancer cells to support their sustained growth and survival. Therefore, inhibitors of amino acid transporters, such as L-type amino acid transporter 1 (LAT1) have been developed. In this study, a previously reported LAT1-inhibitor (KMH-233) was studied for its hemocompatibility and toxicity towards human umbilical vein endothelial cells (HUVEC) and human aortic smooth muscle cells (AoSMCs). Furthermore, the cytotoxic effects against human breast adenocarcinoma cells (MCF-7) and its ability to affect mammalian (or mechanistic) target of rapamycin (mTOR) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling were evaluated. Moreover, the effects of this inhibitor to modulate LAT1 function on the cell surface and the brain amino acid homeostasis were evaluated after intraperitoneal (i.p.) administration of LAT1-inhibitor (23 µmol/kg) in mice. The results showed that LAT1-inhibitor (KMH-233) is hemocompatible at concentrations below 25 µM and it does not affect coagulation in plasma. However, it can reduce the total protein amount of mTOR and NF-κB, resulting in increased apoptosis in LAT1-expressing cancer cells. Most importantly, the inhibitor did not affect mouse brain levels of L-Leu, L-Tyr or L-Trp or modulate the function of LAT1 on the MCF-7 cell surface. Therefore, this inhibitor can be considered as a safe but effective anti-cancer agent. However, due to the compensative mechanism of cancer cells for their increased amino acid demand, this compound is most effective inducing apoptosis when used in combinations with other chemotherapeutics, such as protease inhibitor, bestatin, as demonstrated in this study.