NCT-503 |
| Katalog-Nr.GC15943 |
NCT-503 ist ein Phosphoglycerat-Dehydrogenase (PHGDH)-Hemmer mit einem IC50-Wert von 2,5 μM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1916571-90-8
Sample solution is provided at 25 µL, 10mM.
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NCT-503 is a phosphoglycerate dehydrogenase (PHGDH) inhibitor with an IC50 of 2.5 µM[1]
Treatment of three PHGDH-independent cell lines and five PHGDHdependent cell lines with NCT-503 demonstrated that NCT-503 had EC50 values of 8-16 μM for the PHGDH-dependent cell lines, and no toxicity toward other PHGDH-independent cell lines [1]. When determined the GI50 of NCT-503 in the MHCC97L cell line and found that treatment of NCT-503 significantly reduced the relative ratio of NADPH/NADP+ in cells. NCT-503 could double the number of the apoptotic cells induced by Sorafenib[2]
Primary MM cells are sensitive to doses of the PHGDH inhibitor NCT-503, that are tolerated by PBMCs[4].PHGDH level was significantly increased in the lung adenocarcinoma PC9ER4 cells that acquired resistance to erlotinib. Perturbation of PHGDH by NCT-503, augmented the tumoricidal effect and restored sensitivity to erlotinib in cell lines and xenografts. ROS stress and DNA damage marker γH2AX were enhanced by NCT-503 [3].The combination treatment of NCT-503 and Physcion substantially inhibited hepatocellular carcinoma growth in vitro and in vivo[7]
In mice, NCT-503 exhibits favorable absorption, distribution, metabolism and excretion (ADME) properties. NCT-503 has good exposure, half-life (2.5 hr) and Cmax (20 uM in plasma) following intraperitoneal administration with significant partitioning into the liver and brain. NCT-503 treatment reduces the growth and weight of PHGDH-dependent MDA-MB-468 xenografts but does not affect the growth or weight of PHGDH-independent MDA-MB-231 xenografts[1].In C57BL/KaLwRij mice were injected with 5T33MM cells model, NCT-503 treatment did not reduce tumor load at the doses used but reduced tumor growth in combination with bortezomib[4,5].Adding NCT-503 to the diet of mice increased body weight and liver weight, and increased triglyceride content in liver. NCT-503 supplementation significantly inhibited PHGDH activity and decreased the serine content in the liver[6].Treatment of murine and human lung fibroblasts with NCT-503 decreased TGF-β-induced collagen protein synthesis. Mice treated with the PHGDH inhibitor NCT-503 beginning 7 days after intratracheal instillation of bleomycin had attenuation of lung fibrosis[8]
References:
[1]: Pacold ME, Brimacombe KR, et,al. A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate. Nat Chem Biol. 2016 Jun;12(6):452-8. doi: 10.1038/nchembio.2070. Epub 2016 Apr 25. Erratum in: Nat Chem Biol. 2016 Jul 19;12 (8):656. PMID: 27110680; PMCID: PMC4871733.
[2]: Wei L, Lee D, et,al. Genome-wide CRISPR/Cas9 library screening identified PHGDH as a critical driver for Sorafenib resistance in HCC. Nat Commun. 2019 Oct 15;10(1):4681. doi: 10.1038/s41467-019-12606-7. PMID: 31615983; PMCID: PMC6794322.
[3]: Dong JK, Lei HM, et,al. Overcoming erlotinib resistance in EGFR mutation-positive lung adenocarcinomas through repression of phosphoglycerate dehydrogenase. Theranostics. 2018 Feb 12;8(7):1808-1823. doi: 10.7150/thno.23177. Erratum in: Theranostics. 2021 Feb 9;11(8):3963. PMID: 29556358; PMCID: PMC5858502.
[4]: Elsaadi S, Steiro I, et,al. Targeting phosphoglycerate dehydrogenase in multiple myeloma. Exp Hematol Oncol. 2021 Jan 4;10(1):3. doi: 10.1186/s40164-020-00196-w. PMID: 33397437; PMCID: PMC7784327.
[5]: Dong JK, Lei HM, et,al. Overcoming erlotinib resistance in EGFR mutation-positive lung adenocarcinomas through repression of phosphoglycerate dehydrogenase. Theranostics. 2018 Feb 12;8(7):1808-1823. doi: 10.7150/thno.23177. Erratum in: Theranostics. 2021 Feb 9;11(8):3963. PMID: 29556358; PMCID: PMC5858502.
[6]: He L, Liu Y, et,al. Exogenous and Endogenous Serine Deficiency Exacerbates Hepatic Lipid Accumulation. Oxid Med Cell Longev. 2021 Oct 19;2021:4232704. doi: 10.1155/2021/4232704. PMID: 34712382; PMCID: PMC8548146.
[7]: Dewdney B, Alanazy M, et,al. The effects of fructose and metabolic inhibition on hepatocellular carcinoma. Sci Rep. 2020 Oct 7;10(1):16769. doi: 10.1038/s41598-020-73653-5. PMID: 33028928; PMCID: PMC7541473.
[8]:Hamanaka RB, Nigdelioglu R, et,al. Inhibition of Phosphoglycerate Dehydrogenase Attenuates Bleomycin-induced Pulmonary Fibrosis. Am J Respir Cell Mol Biol. 2018 May;58(5):585-593. doi: 10.1165/rcmb.2017-0186OC. PMID: 29019702; PMCID: PMC5946329
| Cell experiment [1]: | |
|
Cell lines |
MDA-MB-468 cells |
|
Preparation Method |
Cells were pretreated with 10 μM compound or an equivalent volume of DMSO in RPMI for 1 h. |
|
Reaction Conditions |
10 μM NCT-503,1h |
|
Applications |
NCT-503 treatment did not change intracellular glucose concentration |
| Animal experiment [2]: | |
|
Animal models |
Female NOD.CB17-Prkdcscid/J mice, 6–8 weeks old |
|
Preparation Method |
NCT-503 was prepared in a vehicle of 5% ethanol, 35% PEG 300, and 60% of an aqueous 30% hydroxypropyl-β-cyclodextrin (Sigma) solution, and injected intraperitoneally once daily. |
|
Dosage form |
30 mg/kg NCT-503 injected intraperitoneally once daily |
|
Applications |
NCT-503 treatment reduced the growth and weight of PHGDH-dependent MDA-MB-468 xenografts but did not affect those of PHGDH-independent MDA-MB-231 xenografts. PHGDH inhibition(NCT-503) also selectively increased necrosis in MDA-MB-468 but not MDA-MB-231 xenografts . Importantly, mice treated with the compound did not lose weight during the 24d treatment. Levels of NCT-503 in tumors were 3 μM at the conclusion of the experiment, validating exposure of the tumor to compound. |
|
References: [1]. Pacold ME, Brimacombe KR,et,al. A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate. Nat Chem Biol. 2016 Jun;12(6):452-8. doi: 10.1038/nchembio.2070. Epub 2016 Apr 25. Erratum in: Nat Chem Biol. 2016 Jul 19;12 (8):656. PMID: 27110680; PMCID: PMC4871733. |
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| Cas No. | 1916571-90-8 | SDF | |
| Chemical Name | N-(4,6-dimethyl-2-pyridinyl)-4-[[4-(trifluoromethyl)phenyl]methyl]-1-piperazinecarbothioamide | ||
| Canonical SMILES | S=C(N1CCN(CC2=CC=C(C(F)(F)F)C=C2)CC1)NC3=NC(C)=CC(C)=C3 | ||
| Formula | C20H23F3N4S | M.Wt | 408.5 |
| Löslichkeit | ≥ 40.9mg/mL in DMSO | 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. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.448 mL | 12.2399 mL | 24.4798 mL |
| 5 mM | 0.4896 mL | 2.448 mL | 4.896 mL |
| 10 mM | 0.2448 mL | 1.224 mL | 2.448 mL |
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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. )
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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.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 32 reference(s) in Google Scholar.)
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