JPH203 free base
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MedKoo CAT#: 406760

CAS#: 1037592-40-7 (free base)

Description: JPH203, also known as KYT-0353, is a potent and selective LAT1 selective ( L-type amino acid transporter 1) inhibitor. JPH203 can very potently inhibit l-leucine uptake. JPH203 inhibits YD-38 cell growth. JPH203 up-regulated the population of apoptotic YD-38 cells through the activation of apoptotic factors, including caspases and PARP.


Chemical Structure

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JPH203 free base
CAS# 1037592-40-7 (free base)

Theoretical Analysis

MedKoo Cat#: 406760
Name: JPH203 free base
CAS#: 1037592-40-7 (free base)
Chemical Formula: C23H19Cl2N3O4
Exact Mass: 471.0753
Molecular Weight: 472.322
Elemental Analysis: C, 58.49; H, 4.05; Cl, 15.01; N, 8.90; O, 13.55

Price and Availability

Size Price Availability Quantity
10.0mg USD 150.0 Ready to ship
25.0mg USD 250.0 Ready to ship
50.0mg USD 450.0 Ready to ship
100.0mg USD 750.0 Ready to ship
200.0mg USD 1250.0 Ready to ship
500.0mg USD 2650.0 Ready to ship
1.0g USD 3750.0 2 weeks
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Related CAS #: 1597402-27-1 (2HCl)   1037592-40-7 (free base)   1597402-28-2 (complex with beta cyclodextrin)    

Synonym: JPH-203; JPH 203; KYT-0353; KYT 0353; KYT0353; nanvuranlat

IUPAC/Chemical Name: (S)-2-amino-3-(4-((5-amino-2-phenylbenzo[d]oxazol-7-yl)methoxy)-3,5-dichlorophenyl)propanoic acid

InChi Key: XNRZJPQTMQZBCE-SFHVURJKSA-N

InChi Code: InChI=1S/C23H19Cl2N3O4/c24-16-6-12(8-18(27)23(29)30)7-17(25)21(16)31-11-14-9-15(26)10-19-20(14)32-22(28-19)13-4-2-1-3-5-13/h1-7,9-10,18H,8,11,26-27H2,(H,29,30)/t18-/m0/s1

SMILES Code: O=C(O)[C@@H](N)CC1=CC(Cl)=C(OCC2=C(OC(C3=CC=CC=C3)=N4)C4=CC(N)=C2)C(Cl)=C1

Appearance: White to off-white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Slightly soluble in DMSO (50mg/mL), not soluble in water. Soluble in 5% hydrochloride

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO with a few drops of 5%HCl

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: JPH203 is a L-type amino acid transporter 1 (LAT-1) inhibitor.
In vitro activity: The specific inhibition of LAT1 with JPH203 decreased LS174T proliferation by 60% (Fig. 3A and B, left). Consistent with the results for mTORC1 and GCN2 activity, LS174T-CD98KOand A549-CD98KD cells were able to maintain their proliferation at the same level as WT cells (Fig. 3A and B and Supplementary Fig. S3C). Furthermore, it was confirmed that this LAT1KO-specific antiproliferative effect (70% reduction) was observed in 3D culture assays (Fig. 3C). These findings demonstrate the essential role of LAT1 for maintenance of tumor cell AA homeostasis and proliferation. Reference: Cancer Res. 2016 Aug 1;76(15):4481-92. https://cancerres.aacrjournals.org/content/76/15/4481.long
In vivo activity: Thyroid tumorigenesis was induced in 6-weeks old adult BrafCA/+;Pik3caLat/+;Thyro::CreERT2 mice by tamoxifen injection, which results in thyrocyte-specific expression of BRAFV600E and PIK3CAH1047R. A cohort of 12 mice was separated into two groups that were treated with either vehicle or 50 mg/kg JPH203 i.p. daily for five days per week during 6.5 weeks (Fig. 5a). Weekly ultrasound imaging revealed that JPH203 exerted an arrest of tumor growth already after 14 days of treatment, whereas tumors of vehicle-treated mice continued to grow until the end of the experiment (Fig. 5c). This data shows that LAT1 plays a critical role in tumor growth in mice, suggesting that LAT1 helps cells grow in the physiological environment that is low in amino acids. Reference: J Exp Clin Cancer Res. 2018 Sep 21;37(1):234. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150977/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 15.23 32.25
DMSO:PBS (pH 7.2) (1:4) 0.2 4.23

Preparing Stock Solutions

The following data is based on the product molecular weight 472.322 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Oda K, Hosoda N, Endo H, Saito K, Tsujihara K, Yamamura M, Sakata T, Anzai N, Wempe MF, Kanai Y, Endou H. 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. 2. Cormerais Y, Giuliano S, LeFloch R, Front B, Durivault J, Tambutté E, Massard PA, de la Ballina LR, Endou H, Wempe MF, Palacin M, Parks SK, Pouyssegur J. Genetic Disruption of the Multifunctional CD98/LAT1 Complex Demonstrates the Key Role of Essential Amino Acid Transport in the Control of mTORC1 and Tumor Growth. Cancer Res. 2016 Aug 1;76(15):4481-92. doi: 10.1158/0008-5472.CAN-15-3376. Epub 2016 Jun 14. Erratum in: Cancer Res. 2017 Jul 1;77(13):3721. PMID: 27302165. 3. Häfliger P, Graff J, Rubin M, Stooss A, Dettmer MS, Altmann KH, Gertsch J, Charles RP. The LAT1 inhibitor JPH203 reduces growth of thyroid carcinoma in a fully immunocompetent mouse model. J Exp Clin Cancer Res. 2018 Sep 21;37(1):234. doi: 10.1186/s13046-018-0907-z. PMID: 30241549; PMCID: PMC6150977.
In vitro protocol: 1. Oda K, Hosoda N, Endo H, Saito K, Tsujihara K, Yamamura M, Sakata T, Anzai N, Wempe MF, Kanai Y, Endou H. 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. 2. Cormerais Y, Giuliano S, LeFloch R, Front B, Durivault J, Tambutté E, Massard PA, de la Ballina LR, Endou H, Wempe MF, Palacin M, Parks SK, Pouyssegur J. Genetic Disruption of the Multifunctional CD98/LAT1 Complex Demonstrates the Key Role of Essential Amino Acid Transport in the Control of mTORC1 and Tumor Growth. Cancer Res. 2016 Aug 1;76(15):4481-92. doi: 10.1158/0008-5472.CAN-15-3376. Epub 2016 Jun 14. Erratum in: Cancer Res. 2017 Jul 1;77(13):3721. PMID: 27302165.
In vivo protocol: 1. Häfliger P, Graff J, Rubin M, Stooss A, Dettmer MS, Altmann KH, Gertsch J, Charles RP. The LAT1 inhibitor JPH203 reduces growth of thyroid carcinoma in a fully immunocompetent mouse model. J Exp Clin Cancer Res. 2018 Sep 21;37(1):234. doi: 10.1186/s13046-018-0907-z. PMID: 30241549; PMCID: PMC6150977.

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1. Morio H, Reien Y, Hirayama Y, Hashimoto H, Anzai N. Protein kinase C activation upregulates human L-type amino acid transporter 2 function. J Physiol Sci. 2021 Mar 31;71(1):11. doi: 10.1186/s12576-021-00795-0. PMID: 33789576.

1: Otsuki H, Kimura T, Yamaga T, Kosaka T, Suehiro JI, Sakurai H. Prostate Cancer Cells in Different Androgen Receptor Status Employ Different Leucine Transporters. Prostate. 2016 Oct 3. doi: 10.1002/pros.23263. [Epub ahead of print] PubMed PMID: 27696482.

2: Cormerais Y, Giuliano S, LeFloch R, Front B, Durivault J, Tambutté E, Massard PA, de la Ballina LR, Endou H, Wempe MF, Palacin M, Parks SK, Pouyssegur J. Genetic Disruption of the Multifunctional CD98/LAT1 Complex Demonstrates the Key Role of Essential Amino Acid Transport in the Control of mTORC1 and Tumor Growth. Cancer Res. 2016 Aug 1;76(15):4481-92. doi: 10.1158/0008-5472.CAN-15-3376. PubMed PMID: 27302165.

3: Ueno S, Kimura T, Yamaga T, Kawada A, Ochiai T, Endou H, Sakurai H. Metformin enhances anti-tumor effect of L-type amino acid transporter 1 (LAT1) inhibitor. J Pharmacol Sci. 2016 Jun;131(2):110-7. doi: 10.1016/j.jphs.2016.04.021. PubMed PMID: 27262901.

4: Rosilio C, Nebout M, Imbert V, Griessinger E, Neffati Z, Benadiba J, Hagenbeek T, Spits H, Reverso J, Ambrosetti D, Michiels JF, Bailly-Maitre B, Endou H, Wempe MF, Peyron JF. 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. 2015 Jun;29(6):1253-66. doi: 10.1038/leu.2014.338. PubMed PMID: 25482130.

5: Yun DW, Lee SA, Park MG, Kim JS, Yu SK, Park MR, Kim SG, Oh JS, Kim CS, Kim HJ, Kim JS, Chun HS, Kanai Y, Endou H, Wempe MF, Kim DK. 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. PubMed PMID: 24492461.

6: Toyoshima J, Kusuhara H, Wempe MF, Endou H, Sugiyama Y. Investigation of the role of transporters on the hepatic elimination of an LAT1 selective inhibitor JPH203. J Pharm Sci. 2013 Sep;102(9):3228-38. doi: 10.1002/jps.23601. PubMed PMID: 23712732.

7: Wempe MF, Rice PJ, Lightner JW, Jutabha P, Hayashi M, Anzai N, Wakui S, Kusuhara H, Sugiyama Y, Endou H. Metabolism and pharmacokinetic studies of JPH203, an L-amino acid transporter 1 (LAT1) selective compound. Drug Metab Pharmacokinet. 2012;27(1):155-61. PubMed PMID: 21914964.

8: Oda K, Hosoda N, Endo H, Saito K, Tsujihara K, Yamamura M, Sakata T, Anzai N, Wempe MF, Kanai Y, Endou H. 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. PubMed PMID: 19900191.



Additional Information

The intellectual property of JPH203 belongs to J-Pharma and Dr. Hitoshi Endou. The related patents are JP4705756, EP1481965, ZL03803549, KR100948278, AU2003208105, CA2475435, US7345068. This product is not sold to customers in Japan, UK, France, Germany, Switzerland, China, South Korea, Australia and Canada.

In the United States, customer may buy this product only if the customer is engaged in IND (Investigational New Drug application) or NDA (New Drug Application) for obtaining a marketing approval of JPH203.