JPH203 (KYT-0353) (Synonyms: KYT-0353) |
Catalog No.GC32690
One-Click Copy Product Info
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JPH203 (KYT-0353) is an orally active selective inhibitor of L-type amino acid transporter 1 (LAT1). JPH203 inhibits tumor cell growth (IC50=0.06μM) and the uptake of essential amino acids such as leucine (IC50=4.1μM).
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Cas No.: 1037592-40-7
Sample solution is provided at 25 µL, 10mM.
JPH203 (KYT-0353) is an orally active selective inhibitor of L-type amino acid transporter 1 (LAT1). JPH203 inhibits tumor cell growth (IC50=0.06μM) and the uptake of essential amino acids such as leucine (IC50=4.1μM). JPH203 downregulates the mTORC1 pathway to suppress protein synthesis and cell proliferation. JPH203 can be used in research on various malignant tumors including prostate cancer, biliary tract cancer, colorectal cancer, pancreatic cancer, and anaplastic thyroid cancer[1-4].
In vitro, treatment of castration-resistant prostate cancer cells (C4-2, PC-3, LNCaP) with JPH203 (10-50μM) for 12-72h inhibited cell proliferation, migration, and invasion, and suppressed activation of the Wnt/β-catenin signaling pathway[5]. Treatment of C2C12 myotube cells with JPH203 (50μM) for 48h stimulated protein synthesis[6]. Treatment of triple-negative breast cancer cells with JPH203 (5-10μM) for 5min-1h reduced L-Trp and L-Leucine uptake, decreased NAD+ level, increased NADH level, reduced lactate level, and downregulated p-PKM2 and p-LDHA expression[7].
In vivo, intraperitoneal injection of JPH203 (12.5mg/kg) every other day for 16 days in 4T1-BALB/c tumor-bearing mice inhibited tumor growth and reduced essential amino acid levels in tumor tissue[8]. Daily intravenous injection of JPH203 (25mg/kg) for 14 days in B16-F10 melanoma-bearing mice inhibited tumor growth and reduced the formation of lung metastatic nodules[9]. Daily intraperitoneal injection of JPH203 (50mg/kg) for 6.5 weeks (5 days per week) blocked tumor growth in a mouse thyroid cancer model, increased TUNEL-positive apoptotic bodies, and upregulated Atf5 transcription to activate the amino acid stress response[10].
References:
[1] Okunushi K, Furihata T, Morio H,et al. JPH203, a newly developed anti-cancer drug, shows a preincubation inhibitory effect on L-type amino acid transporter 1 function. J Pharmacol Sci. 2020 Sep;144(1):16-22.
[2] Kanai Y. Amino acid transporter LAT1 (SLC7A5) as a molecular target for cancer diagnosis and therapeutics. Pharmacol Ther. 2022 Feb;230:107964.
[3] Choi DW, Kim DK, Kanai Y, 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.
[4] Hu Z, Yan R. Structural basis for the inhibition mechanism of LAT1-4F2hc complex by JPH203. Cell Discov. 2024 Jul 2;10(1):73.
[5] Saito S, Ando K, Sakamoto S, et al. The LAT1 inhibitor JPH203 suppresses the growth of castration-resistant prostate cancer through a CD24-mediated mechanism. Cancer Sci. 2024;115(7):2461-2472.
[6] Takegaki J, Saneyasu T, Honda K, et al. Treatment with L-type amino acid transporter 1 inhibitor JPH203 enhances protein synthesis in C2C12 myotubes. Sci Rep. 2025 Nov 19;15:40805.
[7] Fedoroff MY, Zhao L, Wang S, et al. Amino acid transporter LAT1(SLC7A5) promotes metabolic rewiring in TNBC progression through the L-Trp/QPRT/NAD+ pathway. J Exp Clin Cancer Res. 2025 Jul 3;44:190.
[8] Zhao Y, Pu C, Liu K, et al. Targeting LAT1 with JPH203 to reduce TNBC proliferation and reshape suppressive immune microenvironment by blocking essential amino acid uptake. Amino Acids. 2025;57:27.
[9] Shi Z, Kaneda-Nakashima K, Ohgaki R, et al. Inhibition of cancer-type amino acid transporter LAT1 suppresses B16-F10 melanoma metastasis in mouse models. Sci Rep. 2023 Aug 25;13:13943.
[10] Haffiger P, Graff J, Rubin M, et al. The LAT1 inhibitor JPH203 reduces growth of thyroid carcinoma in a fully immunocompetent mouse model. J Exp Clin Cancer Res. 2018;37:234.
| Cell experiment [1]: | |
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Cell lines |
C4-2 cells, PC-3 cells, LNCaP cells (human castration-sensitive prostate cancer cell line) |
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Preparation Method |
C4-2, PC-3 and LNCaP cells were cultured in RPMI-1640 medium supplemented with 10% FBS at 37°C, 5% CO₂. C4-2 and PC-3 cells were treated with JPH203 at 10 or 30μM for 72h for proliferation assays, 48h for migration and invasion assays, 12h for mTOR signaling pathway analysis, and 24h for RNA-seq analysis. L-leucine uptake assay was performed after 48h of JPH203 treatment. |
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Reaction Conditions |
10μM or 30μM |
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Applications |
JPH203 significantly inhibited [14C]leucine uptake in C4-2 and PC-3 cells. JPH203 inhibited proliferation, migration and invasion of C4-2 and PC-3 cells, with IC50 values of 17.3μM and 12.0μM respectively. JPH203 downregulated phosphorylation of S6K1 and 4EBP1 in the mTOR signaling pathway. Through RNA-seq analysis, JPH203 downregulated CD24 expression in a concentration-dependent manner and suppressed activation of the Wnt/β-catenin signaling pathway in C4-2 cells. |
| Animal experiment [2]: | |
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Animal models |
6-weeks old adult BrafCA;Pik3caLat;Thyro::CreERT2 mice |
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Preparation Method |
Thyroid tumorigenesis was induced by intraperitoneal injection of 1mg tamoxifen dissolved in 100μl peanut oil for five consecutive days. Two months after tumor induction, mice were intraperitoneally administered JPH203 diluted in 40%(w/v) Captisol at a concentration of 7.5mg/ml, 200μl per mouse, 5 consecutive days per week for 6.5 weeks. |
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Dosage form |
50mg/kg; i.p.; 5 days/week for 6.5 weeks |
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Applications |
JPH203 treatment exerted an arrest of tumor growth after 14 days of treatment. JPH203 reduced the number of Ki67-positive cells and BrdU-positive cells in thyroid tumors. JPH203 significantly elevated TUNEL-positive bodies in tumors. JPH203 significantly increased Atf5 transcript levels. JPH203 treatment did not cause significant difference in body weight compared to vehicle-treated mice. |
References: [1] Saito S, Ando K, Sakamoto S, et al. The LAT1 inhibitor JPH203 suppresses the growth of castration-resistant prostate cancer through a CD24-mediated mechanism. Cancer Sci. 2024;115(7):2461-2472. [2] Haffiger P, Graff J, Rubin M, et al. The LAT1 inhibitor JPH203 reduces growth of thyroid carcinoma in a fully immunocompetent mouse model. J Exp Clin Cancer Res. 2018;37:234. | |
| Cas No. | 1037592-40-7 | SDF | |
| Synonyms | 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 | ||
| Formula | C23H19Cl2N3O4 | M.Wt | 472.32 |
| Solubility | 0.1N hydrochloric acid : 7.3 mg/mL (15.46 mM);Methanol : 6.4 mg/mL (13.55 mM);DMSO : <1mg/mL (insoluble or slightly soluble） | 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 | 2.1172 mL | 10.586 mL | 21.1721 mL |
| 5 mM | 423.4 μL | 2.1172 mL | 4.2344 mL |
| 10 mM | 211.7 μL | 1.0586 mL | 2.1172 mL |
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Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 20 reference(s) in Google Scholar.)