JPH203 (KYT-0353)
(Synonyms: KYT-0353) 目录号 : GC32690
JPH203 (KYT-0353) 是一种选择性 L 型氨基酸转运蛋白 1 抑制剂，显着抑制 HT-29 YD-38 和白血病细胞的亮氨酸摄取和细胞生长，IC50 值分别为 0.06 μM 和 4.1 μM 。
Cas No.:1037592-40-7
Sample solution is provided at 25 µL, 10mM.
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JPH203 (KYT-0353), a selective L-type amino acid transporter 1 inhibitor, significantly inhibited leucine uptake and cell growth in HT-29 YD-38 and leukemia cells, with IC50 values of 0.06 μM and 4.1 μM, respectively[1,5].
JPH203 (KYT-0353) can up-regulate the activated forms of pro-apoptotic factors such as Bad, Bax, Bak and caspase-9 and down-regulate anti-apoptotic factors such as Bcl-2,Bcl-xl, activation of mitochondria dependent apoptotic signaling pathway JPH203 (KYT-0353), can distinguish the relative abundance of LAT1 and LAT2, and it has high selectivity for LAT1[2]. JPH203 (KYT-0353) is metabolically stable in liver microsomes of mice, rats, dogs, monkeys and humans[3]. JPH203 (KYT-0353) induced both G2/M and G0/G1 cell cycle arrest, as well as reduced the S phase accompanied by altered expression of the proteins in cell cycle progression: cyclin D1, CDK4, and CDK6[4]. Study on leukemia reported that JPH203 (KYT-0353) induced type ?? cell death, autophagy, followed by caspase-3-dependent apoptosis at 48 h after treatment[6].LAT1 inhibition by JPH203 (KYT-0353) sensitizes cancer cells to radiation by enhancing cellular senescence via mTOR downregulation[7].
In vivo model, using intravenously administered JPH203 (KYT-0353) (12.5 and 25.0 mg/kg), a statistically significant inhibition of growth of HT-29 tumors transplanted to nude mice with only a slight decrease in body weight[4].
References:
[1]: Yun DW, Lee SA, et,al. JPH203, an L-type amino acid transporter 1-selective compound, induces apoptosis of YD-38 human oral cancer cells. J Pharmacol Sci. 2014;124(2):208-17. doi: 10.1254/jphs.13154fp. Epub 2014 Feb 4. PMID: 24492461.
[2]: Choi DW, Kim DK, et,al. JPH203, a selective L-type amino acid transporter 1 inhibitor, induces mitochondria-dependent apoptosis in Saos2 human osteosarcoma cells. Korean J Physiol Pharmacol. 2017 Nov;21(6):599-607. doi: 10.4196/kjpp.2017.21.6.599. Epub 2017 Oct 30. PMID: 29200902; PMCID: PMC5709476.
[3]: Wempe MF, Rice PJ, et,al. Metabolism and pharmacokinetic studies of JPH203, an L-amino acid transporter 1 (LAT1) selective compound. Drug Metab Pharmacokinet. 2012;27(1):155-61. doi: 10.2133/dmpk.dmpk-11-rg-091. Epub 2011 Sep 13. PMID: 21914964.
[4]: Yothaisong S, Dokduang H, et,al. Inhibition of l-type amino acid transporter 1 activity as a new therapeutic target for cholangiocarcinoma treatment. Tumour Biol. 2017 Mar;39(3):1010428317694545. doi: 10.1177/1010428317694545. PMID: 28347255.
[5]: Oda K, Hosoda N, et,al. L-type amino acid transporter 1 inhibitors inhibit tumor cell growth. Cancer Sci. 2010 Jan;101(1):173-9. doi: 10.1111/j.1349-7006.2009.01386.x. Epub 2009 Oct 8. PMID: 19900191.
[6]: Rosilio, C, Nebout, M,et al. L-type amino-acid transporter 1 (LAT1): a therapeutic target supporting growth and survival of T-cell lymphoblastic lymphoma/T-cell acute lymphoblastic leukemia. Leukemia 29, 1253–1266 (2015). https://doi.org/10.1038/leu.2014.338
[7]: Bo T, Kobayashi S, et,al. LAT1 inhibitor JPH203 sensitizes cancer cells to radiation by enhancing radiation-induced cellular senescence. Transl Oncol. 2021 Nov;14(11):101212. doi: 10.1016/j.tranon.2021.101212. Epub 2021 Aug 27. PMID: 34461558; PMCID: PMC8405945.
JPH203 (KYT-0353) 是一种选择性 L 型氨基酸转运蛋白 1 抑制剂，显着抑制 HT-29 YD-38 和白血病细胞的亮氨酸摄取和细胞生长，IC50 值分别为 0.06 μM 和 4.1 μM [1,5]。
JPH203 (KYT-0353) 可上调 Bad、Bax、Bak 和 caspase-9 等促凋亡因子的激活形式，下调 Bcl-2、Bcl-xl、激活线粒体依赖性凋亡信号通路 JPH203 (KYT-0353)，可区分 LAT1 和 LAT2 的相对丰度，对 LAT1[2] 具有高选择性。 JPH203 (KYT-0353) 在小鼠、大鼠、狗、猴子和人类的肝微粒体中代谢稳定[3]。 JPH203 (KYT-0353) 诱导 G2/M 和 G0/G1 细胞周期停滞，并减少 S 期，伴随着细胞周期进程中蛋白质表达的改变:细胞周期蛋白 D1、CDK4 和 CDK6[4 ]。白血病研究报道 JPH203 (KYT-0353) 诱导 ?? 型细胞死亡、自噬，并在处理后 48 h 发生 caspase-3 依赖性细胞凋亡[6]。JPH203 (KYT-0353) 抑制 LAT1 0353) 通过下调 mTOR 增强细胞衰老，使癌细胞对辐射敏感[7]。
体内模型，使用静脉内给药的 JPH203 (KYT-0353)（12.5 和 25.0 mg/kg），对移植到裸鼠的 HT-29 肿瘤的生长有统计学意义的显着抑制，体重仅略有下降[4].
| Cell experiment [1]: | |
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Cell lines |
Saos2 cells |
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Preparation Method |
Colony formation assays were performed by seeding 300 cells/well into 6-well plates for 24 h after growth, cells were treated with 100 M JPH203 (KYT-0353) for 72 h to remove the JPH203 (KYT-0353) treatment and cultured for 10 days with fresh medium. |
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Reaction Conditions |
Treatment with 100 µM JPH203 (KYT-0353) for 72 hours |
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Applications |
JPH203 (KYT-0353) inhibited colony formation in Saos2 cells. |
| Animal experiment [2]: | |
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Animal models |
Six-week-old male athymic BALB/c nude mice |
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Preparation Method |
Mice in treatment group were injected with JPH203 (KYT-0353) intravenously every day for 20 days. |
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Dosage form |
6.3 mg/kg; 12.5 mg/kg; 25 mg/kg JPH203 (KYT-0353) for 20 days |
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Applications |
JPH203 (KYT-0353) (KYT-0353) was administered intravenously daily for 20 days at three different doses starting at day 3 after the injection of cancer cells. On the days 18 and 21, JPH203 (KYT-0353) showed dose-dependent inhibition on tumor growth with significantly inhibited tumor growth in the groups of JPH203 (KYT-0353) at 12.5 mg/kg and 25 mg/kg . |
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References: [1]. Choi DW, Kim DK, et,al. JPH203, a selective L-type amino acid transporter 1 inhibitor, induces mitochondria-dependent apoptosis in Saos2 human osteosarcoma cells. Korean J Physiol Pharmacol. 2017 Nov;21(6):599-607. doi: 10.4196/kjpp.2017.21.6.599. Epub 2017 Oct 30. PMID: 29200902; PMCID: PMC5709476. [2]. Yothaisong S, Dokduang H, et,al. Inhibition of l-type amino acid transporter 1 activity as a new therapeutic target for cholangiocarcinoma treatment. Tumour Biol. 2017 Mar;39(3):1010428317694545. doi: 10.1177/1010428317694545. PMID: 28347255. |
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| Cas No. | 1037592-40-7 | SDF | |
| 别名 | KYT-0353 | ||
| Canonical SMILES | N[C@@H](CC1=CC(Cl)=C(C(Cl)=C1)OCC2=C(OC(C3=CC=CC=C3)=N4)C4=CC(N)=C2)C(O)=O | ||
| 分子式 | C23H19Cl2N3O4 | 分子量 | 472.32 |
| 溶解度 | 0.1N hydrochloric acid : 7.3 mg/mL (15.46 mM);Methanol : 6.4 mg/mL (13.55 mM);DMSO : < 1 mg/mL (insoluble or slightly soluble) | 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 | 2.1172 mL | 10.586 mL | 21.1721 mL |
| 5 mM | 0.4234 mL | 2.1172 mL | 4.2344 mL |
| 10 mM | 0.2117 mL | 1.0586 mL | 2.1172 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