| Targets |
Human 3-phosphoglycerate dehydrogenase (PHGDH). NCT-502 inhibits PHGDH, which is the first and rate-limiting enzyme in the serine biosynthesis pathway, thereby reducing serine production and inhibiting the growth of cancer cells that are dependent on this pathway.
|
|---|---|
| ln Vitro |
NCT-502 has an EC50 of 15.2 μM, making it cytotoxic to MDA-MB-468[1].
NCT-502 inhibits PHGDH with an IC50 of 3.7 µM. It is cytotoxic to PHGDH-dependent cancer cells and reduces glucose-derived serine production. It is inactive against a panel of other dehydrogenases and shows minimal cross-reactivity with GPCRs. |
| ln Vivo |
Specific in vivo activity data for NCT-502 are not detailed in the available literature. As a PHGDH inhibitor, it would be expected to have antitumor activity in vivo in PHGDH-dependent cancers. However, specific animal model studies are not described.
|
| Enzyme Assay |
The in vitro enzyme inhibition assay for NCT-502 involves measuring the activity of PHGDH in the presence of varying concentrations of the compound. The enzyme is incubated with its substrate (3-phosphoglycerate) and cofactor (NAD+), and the production of phosphohydroxypyruvate is quantified. The IC50 is determined from the dose-response curve.
|
| Cell Assay |
Specific in vitro cell-based assay protocols for NCT-502 are not detailed. Its cytotoxic effects can be assessed in PHGDH-dependent cancer cell lines by treating cells with NCT-502 and measuring cell viability using standard assays such as MTT or CellTiter-Glo. Serine production can also be measured using mass spectrometry.
|
| Animal Protocol |
Specific in vivo animal model protocols for NCT-502 are not described. To evaluate its in vivo efficacy, NCT-502 could be administered to mouse xenograft models of PHGDH-dependent cancers. Tumor growth inhibition would be measured.
|
| ADME/Pharmacokinetics |
Pharmacokinetic data for NCT-502 are not reported in the available literature. As a research compound, its absorption, distribution, metabolism, and excretion (ADME) properties have not been extensively characterized.
|
| Toxicity/Toxicokinetics |
Specific toxicological data for NCT-502 are not available. As a research compound, its safety profile has not been comprehensively characterized. Toxicity studies would be required to determine its safety margin.
|
| References | |
| Additional Infomation |
N-(4,6-dimethyl-2-pyridyl)-4-[5-(trifluoromethyl)-2-pyridyl]-1-piperazine thiocarboxamide is a member of the piperazine and pyridine classes of compounds.
NCT-502 is a research tool for studying cancer metabolism, specifically the serine biosynthesis pathway, and for investigating the potential of PHGDH as a therapeutic target for cancer. It is used to explore metabolic vulnerabilities in tumors reliant on PHGDH-driven pathways. It is not an approved therapeutic agent. |
| Molecular Formula |
C18H20F3N5S
|
|---|---|
| Molecular Weight |
395.445112228394
|
| Exact Mass |
395.139
|
| CAS # |
1542213-00-2
|
| PubChem CID |
49853368
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
3.5
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
27
|
| Complexity |
510
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
N1(C(NC2=NC(C)=CC(C)=C2)=S)CCN(C2=NC=C(C(F)(F)F)C=C2)CC1
|
| InChi Key |
HHKPPMSUPATMKP-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C18H20F3N5S/c1-12-9-13(2)23-15(10-12)24-17(27)26-7-5-25(6-8-26)16-4-3-14(11-22-16)18(19,20)21/h3-4,9-11H,5-8H2,1-2H3,(H,23,24,27)
|
| Chemical Name |
N-(4,6-dimethylpyridin-2-yl)-4-[5-(trifluoromethyl)pyridin-2-yl]piperazine-1-carbothioamide
|
| Synonyms |
NCT502; NCT 502; NCT-502
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~130 mg/mL (~328.74 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (5.49 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.17 mg/mL (5.49 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5288 mL | 12.6438 mL | 25.2876 mL | |
| 5 mM | 0.5058 mL | 2.5288 mL | 5.0575 mL | |
| 10 mM | 0.2529 mL | 1.2644 mL | 2.5288 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.
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