| 包装 | 价格(元) |
| 5mg | 电议 |
| 10mg | 电议 |
| 25mg | 电议 |
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 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. |
| 产品描述 | 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: |
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