| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
SLC6A19[1].
JNT-517 specifically targets SLC6A19 (B0AT1), a sodium-dependent neutral amino acid transporter expressed in the kidney and intestine. By allosterically inhibiting this transporter, JNT-517 blocks the reabsorption of neutral amino acids, including phenylalanine, in the proximal tubules of the kidney. This leads to increased urinary excretion of phenylalanine and reduced plasma phenylalanine levels. The compound's selectivity for SLC6A19 over other amino acid transporters is a key feature that minimizes off-target effects. SLC6A19 is a well-validated target for PKU treatment. |
|---|---|
| ln Vitro |
In vitro studies have shown that JNT-517 is a highly potent and selective inhibitor of human SLC6A19, with an IC50 of 47 nM in the isoleucine transport assay. The compound exhibits excellent selectivity for SLC6A19 over other SLC6 family transporters. In cell-based assays, JNT-517 effectively inhibits the uptake of neutral amino acids, including phenylalanine and isoleucine, into cells expressing SLC6A19. The compound's allosteric mechanism of action allows for potent inhibition without competing with the natural substrates of the transporter. These in vitro properties support its development as a therapeutic agent for PKU.
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| ln Vivo |
In vivo studies in a mouse model of phenylketonuria have demonstrated that JNT-517 treatment increases urinary excretion of phenylalanine and significantly reduces plasma phenylalanine levels. The compound is orally bioavailable and shows good exposure following oral administration. These in vivo efficacy data support the potential of JNT-517 as a novel therapeutic approach for PKU. The compound is currently being evaluated in clinical trials for the treatment of phenylketonuria. Further studies are ongoing to characterize its full pharmacological profile.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for JNT-517 typically involve measuring the inhibition of SLC6A19-mediated amino acid transport in cell lines expressing the transporter. A typical assay protocol includes incubating cells with radiolabeled or fluorescently labeled isoleucine or phenylalanine in the presence of varying concentrations of JNT-517. The uptake is measured, and the IC50 is calculated from the concentration-response curve. The compound's allosteric binding mode can be confirmed through radioligand binding studies or kinetic analyses that demonstrate non-competitive inhibition.
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| Cell Assay |
In vitro cell-based experiments for JNT-517 involve the use of cell lines engineered to express human SLC6A19. Cells are plated in 96-well plates and incubated with the compound at various concentrations. Amino acid uptake is measured using radiolabeled substrates or fluorescent probes. The inhibition of uptake is quantified, and the IC50 is determined. Cytotoxicity assays are also performed to ensure that the observed effects are not due to cell death. These cell-based assays are essential for characterizing the compound's potency and selectivity.
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| Animal Protocol |
In vivo animal experiments for JNT-517 are typically conducted in a mouse model of phenylketonuria (PKU), such as the PAH-deficient mouse. Animals are administered JNT-517 orally at various doses, and blood and urine samples are collected at different time points. Plasma phenylalanine levels are measured using LC-MS/MS or enzymatic assays. Urinary phenylalanine excretion is also quantified. The compound's efficacy in reducing plasma phenylalanine levels is assessed, and pharmacokinetic parameters are determined from plasma concentration data.
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| ADME/Pharmacokinetics |
JNT-517 is orally bioavailable with favorable pharmacokinetic properties. Following oral administration, the compound is absorbed and distributed to target tissues, including the kidney. Its half-life and clearance are consistent with once-daily dosing. The compound's pharmacokinetic profile supports its development as an oral therapeutic for PKU. Detailed pharmacokinetic data, including Cmax, AUC, and bioavailability, are available from preclinical studies and are being further characterized in clinical trials.
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| Toxicity/Toxicokinetics |
Toxicological studies of JNT-517 have been conducted in preclinical species to support its clinical development. The compound has shown a favorable safety profile in animal studies, with no significant off-target effects due to its high selectivity for SLC6A19. Standard toxicology studies, including acute and repeat-dose toxicity, genotoxicity, and safety pharmacology, have been performed. The compound is well-tolerated at therapeutic doses, and the no-observed-adverse-effect level (NOAEL) has been established for use in clinical trials.
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| References | |
| Additional Infomation |
JNT-517 is a first-in-class allosteric inhibitor of SLC6A19 being developed for the treatment of phenylketonuria. Its CAS number is 2837993-05-0. The compound is in clinical development and has shown promising results in reducing plasma phenylalanine levels in preclinical models and clinical trials. It represents a novel therapeutic approach for PKU that does not require dietary phenylalanine restriction. The compound is for research use only and is not yet approved for human use.
|
| Molecular Formula |
C18H22F4N4O3
|
|---|---|
| Molecular Weight |
418.39
|
| Exact Mass |
418.162
|
| CAS # |
2837993-05-0
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| PubChem CID |
168510630
|
| Appearance |
White to off-white solid powder
|
| LogP |
2.4
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
29
|
| Complexity |
602
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
FC1C=C(C=CC=1CNC(N([C@H]1CN(C(N)=O)CCC1)C1CC1)=O)OC(F)(F)F
|
| InChi Key |
FNRHWODWSBDOOY-CYBMUJFWSA-N
|
| InChi Code |
InChI=1S/C18H22F4N4O3/c19-15-8-14(29-18(20,21)22)6-3-11(15)9-24-17(28)26(12-4-5-12)13-2-1-7-25(10-13)16(23)27/h3,6,8,12-13H,1-2,4-5,7,9-10H2,(H2,23,27)(H,24,28)/t13-/m1/s1
|
| Chemical Name |
(3R)-3-[cyclopropyl-[[2-fluoro-4-(trifluoromethoxy)phenyl]methylcarbamoyl]amino]piperidine-1-carboxamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3901 mL | 11.9506 mL | 23.9011 mL | |
| 5 mM | 0.4780 mL | 2.3901 mL | 4.7802 mL | |
| 10 mM | 0.2390 mL | 1.1951 mL | 2.3901 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Link: https://clinicaltrials.gov/ct2/show/NCT07446400
Conditions:Healthy VolunteersLink: https://clinicaltrials.gov/ct2/show/NCT05781399
Conditions:PhenylketonuriaLink: https://clinicaltrials.gov/ct2/show/NCT06971731
Conditions:Phenylketonuria
Title:A Long-Term Study of JNT-517 in Participants With Phenylketonuria
Status:Recruiting
updateDate:2026-05-01
Ctid:NCT06628128
Link: https://clinicaltrials.gov/ct2/show/NCT06628128
Conditions:Phenylketonuria (PKU)Link: https://clinicaltrials.gov/ct2/show/NCT06637514
Conditions:Phenylketonuria (PKU)Products are for research use only; We do not sell to patients
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