CBR-5884 Chemical Properties

Boiling point:

378.1±42.0 °C(Predicted)

Density 

1.43±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

Soluble in DMSO (up to 50 mg/ml) or in DMF (up to 50 mg/ml).

form 

paste

pka

11.25±0.70(Predicted)

color 

white to beige

Stability:

Stable for 2 years from date of purchase as supplied. Solutions in DMSO or DMF may be stored at -20°C for up to 2 months.

InChI

1S/C14H12N2O4S2/c1-3-19-14(18)11-8(2)10(21-7-15)13(22-11)16-12(17)9-5-4-6-20-9/h4-6H,3H2,1-2H3,(H,16,17)

InChIKey

QBVIRPJBDIZKBC-UHFFFAOYSA-N

SMILES

CC1=C(C(OCC)=O)SC(NC(C2=CC=CO2)=O)=C1SC#N

Safety Information

WGK Germany 

WGK 3

Storage Class

11 - Combustible Solids

Hazard Classifications

Eye Irrit. 2
Skin Irrit. 2
STOT SE 3

CBR-5884 Usage And Synthesis

Description

CBR-5884 (681159-27-3) is a potent and selective inhibitor of 3-phosphoglycerate dehydrogenase (PHGDH), IC50=33 μM.1?The action of PHGDH is the first committed step of serine biosynthesis2?and certain cancer cells overexpress PHGDH3. CBR-5884 inhibits serine biosynthesis in cells with no effect on two other dehydrogenases, lactate dehydrogenase and MDH1 and without general cytotoxic effects up to 40 μM. CBR-5884 is selectively toxic to tumor cells with high serine synthesis activity. A novel tool for selective inhibition of serine biosynthesis in cells which also provides further proof that PHGDH is a viable target for the development of novel anticancer agents.1

Uses

CBR-5884 has been used as a 3-phosphoglycerate dehydrogenase (PHGDH) inhibitor to explore the role of PHGDH in Müller cells from different retinal regions and also used in trypan blue exclusion assay to determine the number of viable MYCN cells.

Biochem/physiol Actions

CBR-5884 is a cell penetrant, potent and selective noncompetitive inhibitor of 3-phosphoglycerate dehydrogenase (PHGDH) that inhibits proliferation of melanoma and breast cancer lines. CBR-5884 inhibits de novo serine synthesis in in cancer cells.

Background

CBR-5884 is a small-molecule inhibitor of phosphoglycerate dehydrogenase, which catalyzes the first step in the serine biosynthesis pathway. An increase in serine biosynthesis supports growth and proliferation of cancer cells, which is seen by amplification and overexpression of PHGDH in some melanoma and breast cancers. CBR-5884 inhibited the proliferation of melanoma and breast cancers that displayed increased levels of serine synthesis, but had no effect on cells that rely on extracellular serine uptake. CBR-5884 disrupted PHGDH oligomerization and decreased serine biosynthesis by 30% in cancer cells. CBR-5884 treatment of teratocarcinoma cells significantly decreased the growth rate in a dose-dependent manner. Inhibition of PHGDH and serine biosynthesis caused accumulation of reactive oxygen species, DNA damage, and apoptosis in leukemic cells. Treating human myeloma cells with CBR-5884 reduced proliferation, while inhibition of PHGDH by CBR-5884 reduced proliferation and sensitized glioblastoma cells to hypoxia-induced cell death.

References

[1] EDOUARD MULLARKY. Identification of a small molecule inhibitor of 3-phosphoglycerate dehydrogenase to target serine biosynthesis in cancers[J]. Proceedings of the National Academy of Sciences of the United States of America, 2016, 113 1: 1778-1783. DOI:10.1073/pnas.1521548113
[2] SNELL K. The duality of pathways for serine biosynthesis is a fallacy[J]. Trends in Biochemical Sciences, 1986, 11 6: Pages 241-243. DOI:10.1016/0968-0004(86)90184-2
[3] GINA M DENICOLA. NRF2 regulates serine biosynthesis in non–small cell lung cancer[J]. Nature genetics, 2015, 47 12: 1475-1481. DOI:10.1038/ng.3421

CBR-5884(681159-27-3)Related Product Information

• Troglitazone
• Geldanamycin
• Imatinib mesylate
• Cantharidin