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Nanvuranlat (JPH203) LAT1 inhibitor

Name: Nanvuranlat (JPH203)
Brand: Selleck Chemicals
SKU: S8667
Availability: InStock
Rating: 5 (26 reviews)

Cat.No.S8667

Nanvuranlat (JPH203, KYT-0353, JPH-203SBECD), a selective L-type amino acid transporter 1 inhibitor, shows a dramatic inhibition of leucine uptake (IC50=0.06 µM) and cell growth (IC50=4.1 µM) in human colon cancer cells (HT-29), human oral cancer cells (YD-38) and leukemic cells.

Chemical Structure

Molecular Weight: 472.32

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability

Quality Control

Batch: Purity: 99.73%

99.73

Related Targets	CD markers AChR Calcium Channel Sodium Channel Potassium Channel GABA Receptor ATPase TRP Channel GluR NMDAR P2 Receptor Proton Pump P-gp CFTR SGLT Chloride Channel MCT GLUT CRM1 VDAC BCRP NKCC OCT NCX OAT VMAT Aquaporin EAAT GlyT GlyR
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Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Incubation Time	Activity Description	PMID
HT-29	Function assay	1 hr	Inhibition of [14C]-L-leucine uptake at LAT1 in human HT-29 cells after 1 hr by liquid scintillation counting, IC50=0.06μM.	27253989
YD-38	Function assay	1 hr	Inhibition of [14C]-L-leucine uptake at LAT1 in human YD-38 cells after 1 hr by liquid scintillation counting, IC50=0.79μM.	27253989
HT-29	Growth inhibition assay	96 hrs	Growth inhibition of human HT-29 cells measured after 96 hrs by Coulter counter based cell counting method, IC50=4.1μM.	27253989
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	472.32	Formula	C₂₃H₁₉Cl₂N₃O₄	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1037592-40-7	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	KYT-0353, JPH-203SBECD			Smiles	C1=CC=C(C=C1)C2=NC3=CC(=CC(=C3O2)COC4=C(C=C(C=C4Cl)CC(C(=O)O)N)Cl)N

Solubility

In vitro
Batch:

5%TFA : 2.31 mg/mL

DMSO : 0.01 mg/mL ( (0.02 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Clear solution	5%DMSO 1 Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.150mg/ml (0.32mM)	Taking the 1 mL working solution as an example, add 50 μL of 3 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	1.180mg/ml (2.50mM)	Taking the 1 mL working solution as an example, add 50 μL of clarified DMSO stock solution of 23.5 mg/ml to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL of ddH2O to make it clear. Volume up to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	2%DMSO 1 98%Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.420mg/ml (0.89mM)	Taking the 1 mL working solution as an example, add 20 μL of 21 mg/ml clear DMSO stock solution to 980 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	LAT1 ^[1] (Cell-free assay)
In vitro	Nanvuranlat (JPH203) completely and slightly inhibited the L-Leucine uptake in YD-38 cells (IC50 value: 0.79 μM) and NHOKs (IC50 value: >100 μM), respectively. It inhibited HT-29 cell growth, generating an apparent IC50 of 4.1 μM, but the IC50 concentration (0.06 μM) needed to inhibit the L-Leucine uptake did not inhibit HT-29 cell growth, which represents a 68-fold difference in susceptibility^[1]. This compound activated the mitochondria-dependent apoptotic signaling pathway by upregulating pro-apoptotic factors, such as Bad, Bax, and Bak, and the active form of caspase-9, and downregulating anti-apoptotic factors, such as Bcl-2 and Bcl-xL in Saos2 human osteosarcoma cells. It can distinguish relative abundance between LAT1 and LAT2, and has high selectivity for LAT1^[2]. JPH203 was metabolically stable in mouse, rat, dog, monkey and human liver microsomal incubations^[3]. It induces 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].
In vivo	Daily intravenous administration of JPH203 (12.5 and 25 mg/kg) significantly inhibited tumor growth in KKU-213 cholangiocarcinoma cell xenografts in the nude mice model in a dose-dependent manner with no statistically significant change in the animal’s body weight and with no differences in the histology and appearance of the internal organs compared with the control group. Thus, this compound shows anti-tumor efficacy in nude mice bearing human cholangiocarcinom (CCA) cell xenografts without general toxicity^[4].
References	https://pubmed.ncbi.nlm.nih.gov/24492461/ https://pubmed.ncbi.nlm.nih.gov/29200902/ https://pubmed.ncbi.nlm.nih.gov/21914964/ https://pubmed.ncbi.nlm.nih.gov/28347255/

Applications

Methods	Biomarkers	Images	PMID
Western blot	p53 / Bad / Bcl-2 / Bcl-xl / Bax / Bak / Cleaved caspase / Cleaved PARP p70S6K / p-P70S6k / p-S6 / S6 / p-ERK / ERK / p-AKT / AKT' p-GCN2 / GCN2 / p-EIF2α / EIF2α / ATF4		29200902
Growth inhibition assay	Cell viability		29200902

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