| Description | JPH203 (KYT-0353) is a potent and specific inhibitor of L-type amino acid transporter protein 1 (LAT-1). JPH203 inhibits cellular uptake of leucine, inhibits cell proliferation, induces apoptosis, and possesses anti-inflammatory and anti-tumor activities. |
| In vitro | 方法：HT-29、S2-LAT1 和 S2-LAT2 细胞用含 14C-leucine 和 JPH203 (0.01-10 µM) 的培养基孵育 1.0 min，使用 scintillation counter 计数细胞裂解物的放射性。结果：JPH203 以浓度依赖的方式抑制 S2-hLAT1 细胞对 14C-leucine 的摄取，IC50 为 0.14 µM。JPH203 几乎不抑制 S2-hL 细胞对 14C-leucine 的摄取，因此具有高的体外 hLAT1 抑制选择性。[1]方法：人骨肉瘤细胞 Saos2 和人成骨细胞 FOB 用 JPH203 (0.01-30 mM) 处理 1-4 天，使用 MTT Assay 检测细胞活力。结果：JPH203 以剂量和时间依赖的方式有效抑制 Saos2 细胞中的细胞增殖。JPH203 仅轻微抑制 FOB 细胞的增殖。[2] |
| In vivo | 方法：为检测体内抗肿瘤活性，将 JPH203 (6.5-25 mg/kg) 静脉注射给携带人结直肠癌肿瘤 HT-29 的 nude 小鼠，每天一次，持续十四天。结果：JPH203 对肿瘤生长具有剂量依赖性抑制作用。6.3、12.5 和 25.0 mg/kg 时的最大抑制率分别为 58.2% (第 42 天)、65.9% (第 30 天) 和 77.2% (第 38 天）。[1]方法：为检测体内抗肿瘤活性，将 JPH203 (50 mg/kg in SBECD) 腹腔注射给富含基质的 CRC 小鼠模型，每天一次，持续十四天。结果：JPH203 治疗显著减少了肿瘤大小和转移，基于 RNA 测序的通路分析表明，不仅肿瘤生长和氨基酸代谢通路，而且基质激活相关通路都受到抑制。[3] |
| Cell experiments | Growth inhibition is evaluated by the MTT assay method. Namely, cell suspensions (1 × 10^4 cells/mL) in a volume of 135 μL are placed into the wells of a flat-bottom 96-well microtiter plate and incubated in the atmosphere of 5% CO2 at 37°C (24 h). Drug solutions (15 μL) at various concentrations are added and incubated (96 h) under the same conditions. Next, MTT (15 μL, 5 mg/mL) dissolved in PBS is added and incubated (4.0 h). The incubation medium containing MTT is aspirated off. Cells are mixed (5 min) with DMSO (200 μL) and optical density read (540 nm) using a microtiter plate reader Emax. Subsequently, IC50 values are determined [1]. |
| Animal experiments | HT-29 tumor blocks are injected subcutaneously to the right flank of male nude mice. After tumor volumes reach 100 to 300 mm3, the mice are divided into groups (n = 6). On the day of grouping (day 0), JPH203 is administered intravenously daily for 14 days at three different doses (6.3, 12.5, and 25.0 mg/kg). Tumor volumes and body weights are measured two or three times a week for 42 days. Tumor volumes are expressed relative to initial tumor volume (day 0). Growth inhibition ratios for each treatment group is obtained from the mean tumor volume of the treated group compared to that of the control group [1]. |
| Synonyms | KYT-0353 |
| molecular weight | 472.32 |
| Molecular formula | C23H19Cl2N3O4 |
| CAS | 1037592-40-7 |
| Storage | store under nitrogen | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility | DMSO: 100 mg/mL (211.7 mM), Sonication is recommended. 5%TFA: 2.31 mg/mL (4.89 mM), Heating at 50℃ is recommended. 5% DMSO+40% PEG300+5% Tween 80+50% Saline: 5 mg/mL, Sonication is recommended. |
| References | 1. Oda K, et al. L-type amino acid transporter 1 inhibitors inhibit tumor cell growth. Cancer Sci. 2010 Jan;101(1):173-9. 2. Choi DW, 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. 3. Otani R, et al. The Anti-Tumor Effect of the Newly Developed LAT1 Inhibitor JPH203 in Colorectal Carcinoma, According to a Comprehensive Analysis. Cancers (Basel). 2023 Feb 22;15(5):1383. |