NCT-503 is an inhibitor of phosphoglycerate dehydrogenase (PHGDH), which catalyzes the first, rate-limiting step of glucose-derived serine synthesis. NCT-503 reduced glucose-derived serine production and suppressed the growth of both PHGDH-dependent cancer cells in culture and in xenograft tumors, and caused G1/S cell cycle arrest in MDA-MB-468 cells. NCT-503 reduced the incorporation of one-carbon units from glucose-derived and exogenous serine into nucleotides, which may contribute to its anticancer activity. NCT-503 had an IC50 value of 2.5 μM for PHGDH and was inactive against a panel of other dehydrogenases and minimal cross-reactivity in a panel of 168 G-protein-coupled receptors (GPCRs). NCT-503 was found to be noncompetitive with respect to both 3-PG and NAD+, and exhibit good stability (>98% after 48 hrs in assay buffer) and aqueous solubility.
| Cell Experiment | |
|---|---|
| Cell lines | MDA-MB-468, BT-20, MT-3 cells |
| Preparation method | MDA-MB-468, BT-20, MT-3 cells are seeded in white 96-well plates allowed to attach for 24 hours. Cells are treated with NCT-503 for four days. Cell viability is assessed with Cell Titer-Glo and luminescence measured with a plate reader. |
| Concentrations | |
| Incubation time | 4 days |
| Animal Experiment | |
|---|---|
| Animal models | Female NOD.CB17-Prkdcscid/J mice |
| Formulation | 5% ethanol, 35% PEG 300, and 60% of an aqueous 30% hydroxypropyl-β-cyclodextrin solution |
| Dosages | |
| Administration | injected intraperitoneally once daily |
| Molecular Weight | 408.48 |
| Formula | C20H23F3N4S |
| CAS Number | 1916571-90-8 |
| Solubility (25°C) | DMSO 45 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
| Related PHGDH Products |
|---|
| PKUMDL-WQ-2101
PKUMDL-WQ-2101 is a non-NAD+-competing allosteric phosphoglycerate dehydrogenase (PHGDH) inhibitor with an IC50 of 34.8 μM. PKUMDL-WQ-2101 exhibits antitumor activity. |
| PHGDH-inactive
PHGDH-inactive has no activity against PHGDH and serves as a negative control of NCT-502 and NCT-503. |
| NCT-502
NCT-502 is a human phosphoglycerate dehydrogenase (PHGDH) inhibitor, cytotoxic to PHGDH-dependent cancer cells, and reduces glucose-derived serine production, with an IC50 of 3.7 μM against PHGDH. |
| BI-4924
BI-4924 is a lipophilic, highly plasma protein bound selective phosphoglycerate dehydrogenase (PHGDH) inhibitor (IC50=3 nM) with excellent microsomal, as well as hepatocytic stability. |
| BI-4916
BI-4916 is a prodrug of BI-4924. BI-4924 is a NADH/NAD+-competitive PHGDH inhibitor. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.
