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| | NCT-503 Basic information |
| Product Name: | NCT-503 | | Synonyms: | NCT-503;9-(6-aminopyridin-3-yl)-1-(4-fluoro-3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one;NCT 503;NCT503;CS-2612;NCT-503; NCT 503; NCT503.;1-Piperazinecarbothioamide, N-(4,6-dimethyl-2-pyridinyl)-4-[[4-(trifluoromethyl)phenyl]methyl]-;NCT-503 >=98% (HPLC);inhibit,NCT-503,NCT503,Inhibitor | | CAS: | 1916571-90-8 | | MF: | C20H23F3N4S | | MW: | 408.48 | | EINECS: | | | Product Categories: | | | Mol File: | 1916571-90-8.mol |  |
| | NCT-503 Chemical Properties |
| Boiling point | 474.3±55.0 °C(Predicted) | | density | 1.306±0.06 g/cm3(Predicted) | | storage temp. | 2-8°C | | solubility | ≥40.9 mg/mL in DMSO; insoluble in H2O; ≥20.33 mg/mL in EtOH | | form | powder | | pka | 12.99±0.20(Predicted) | | color | white to beige |
| | NCT-503 Usage And Synthesis |
| Description | NCT-503 is an inhibitor of 3-phosphoglycerate dehydrogenase (PHGDH), inhibiting serine synthesis from 3-phosphoglycerate in cells with an IC50 value of 2.5 μM. It has been shown to reduce the production of glucose-derived serine in cells and to suppress the growth of PHGDH-dependent MDA-MB-468 cancer cells both in vitro and in mice bearing orthotopic xenograft tumors. | | Uses | NCT-503 is a novel inhibitor of human Phosphoglycerate Dehydrogenase (PHGDH). | | Biochem/physiol Actions | 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. | | in vitro | nct-503 was identified as an inhibitor of phgdh and was found to be inactive against a panel of other dehydrogenases and showed minimal cross-reactivity in a panel of g-protein-coupled receptors. in addition, 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]. | | in vivo | to evaluate nct-503 in-vivo activity, nod.scid mice bearing mda-mb-231 and mda-mb-468 orthotopic xenografts were treated with vehicle or nct-503. results showed that nct-503 treatment reduced the growth and weight of phgdh-dependent xenografts but did not affect those of phgdh-independent xenografts. importantly, mice treated with nct-503 did not lose weight during the 24-d treatment in spite of the potential systemic toxicities of inhibiting serine biosynthesis [1]. | | IC 50 | 2.5 μm for inhibiting serine synthesis from 3-phosphoglycerate in cells | | references | [1] pacold, m. e.,brimacombe, k.r.,chan, s.h., et al. a phgdh inhibitor reveals coordination of serine synthesis and one-carbon unit fate. nature chemical biology 12(6), 452-458 (2016). |
| | NCT-503 Preparation Products And Raw materials |
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