CBR-5884 |
Catalog No.GC13336 |
Le CBR-5884 est un inhibiteur actif et sélectif de la phosphoglycérate déshydrogénase (PHGDH) avec une IC50 de 33 μM. Le CBR-5884 inhibe la synthèse de novo de la sérine dans les cellules cancéreuses et est sélectivement toxique pour les lignées cellulaires cancéreuses ayant une activité biosynthétique élevée de la sérine. Le CBR-5884 inhibe sélectivement la prolifération des lignées de mélanome et de cancer du sein qui ont une forte propension À la synthèse de sérine.
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Cas No.: 681159-27-3
Sample solution is provided at 25 µL, 10mM.
CBR-5884 is a selective inhibitor of 3-phosphoglycerate dehydrogenase (PHGDH) with IC50 of 7 μM. PHGDH catalyzes the first committed step of serine biosynthesis, is overexpressed in tumors and cancer cell lines via focal amplification and nuclear factor erythroid-2-related factor 2 (NRF2)-mediated up-regulation. So CBR-5884 can inhibit de novo serine synthesis in cancer cells.
CBR5884 selectively inhibits the proliferation of breast and melanoma cancer lines that have a high propensity for serine synthesis but has no effect on lines that rely on extracellular serine uptake. CBR-5884 is a noncompetitive and time-dependent inhibitor of PHGDH and disrupts its oligomerization state. The dose at which CBR-5884 has an effect on serine labeling was consistent with the in vitro biochemical IC50 of 33 ± 12 μM for PHGDH. At such concentrations, CBR-5884 has no effect on two other NAD+-dependent dehydrogenases, lactate dehydrogenase (LDH) and MDH1. The Ki value are 50 ± 20 μM and 50 ± 3 μM for 3-PG and NAD+, respectively. CBR-5884 is not generally cytotoxic at concentrations up to 40 μM as determined by two independent cellular viability assays. Treating the breast lines with CBR-5884 in serine-replete media inhibited growth of the four lines that grew without extracellular serine in a dose-dependent manner, with growth inhibition ranging from 35% to 60% at 30 μM CBR-5884. Serine depletion increases the efficacy of CBR-5884 in lines already sensitive under serine-replete conditions as evidenced by an 80–90% decrease in proliferation with 30 μM CBR-5884. [1]
Reference:
1.Identification of a small molecule inhibitor of 3-phosphoglycerate dehydrogenase to target serine biosynthesis in cancers. Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):1778-83.
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