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Literature summary for 1.1.1.95 extracted from

  • Zhao, X.; Fu, J.; Du, J.; Xu, W.
    The role of D-3-phosphoglycerate dehydrogenase in Cancer (2020), Int. J. Biol. Sci., 16, 1495-1506 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
expression in Escherichia coli Rosetta (DE3) pLysS competent cells Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
2-chloro-4-(5-[(Z)-[2-(ethylcarbamothioyl)hydrazinylidene]methyl]furan-3-yl)benzoic acid i.e. PKUMDL-WQ-2101, specifically binds to the enzyme (PHGDH) in PHGDH-amplified breast cancer cells with EC50 values less than 0.010 mM in serine-replete media. Mainly inhibits PHGDH activity by forming hydrogen-bond networks with R134, K57, and T59 of site I and T59, T56, and K57 of site II, respectively Homo sapiens
3-[(E)-(5-cyano-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazenyl]benzoic acid i.e. PKUMDL-WQ-2201, specifically binds to the enzyme (PHGDH) in PHGDH-amplified breast cancer cells with EC50 values less than 0.010 mM in serine-replete media. Mainly inhibits PHGDH activity by forming hydrogen-bond networks with R134, K57, and T59 of site I and T59, T56, and K57 of site II, respectively Homo sapiens
5-[(2-furanylcarbonyl)amino]-3-methyl-4-thiocyanato-2-thiophenecarboxylic acid ethyl ester i.e. CBR-5884, covalent inhibitor that binds to a Cys in the non-active site and disrupts its oligomeric state. CBR-5884 inhibits the growth of cells by 35% to 60% in serine-abundant media, and by 80% to 90% in serine-depleted media at 0.030 mM Homo sapiens
azacoccone E non-competitive inhibitor in a time-dependent manner Homo sapiens
BI-4916
-
Homo sapiens
ixocarpalactone A non-competitive inhibitor relative to the substrate of NAD coenzyme Homo sapiens
N-(4,6-dimethylpyridin-2-yl)-4-(4-(trifluoromethyl)benzyl)piperazine-1-carbothioamide i.e. NCT-503, non-competitive inhibitor in regards to substrates and cofactors, closely binds to the active site Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3-phospho-D-glycerate + NAD+ Homo sapiens
-
3-phosphooxypyruvate + NADH + H+
-
r

Organism

Organism UniProt Comment Textmining
Homo sapiens O43175
-
-

Purification (Commentary)

Purification (Comment) Organism
-
Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3-phospho-D-glycerate + NAD+
-
Homo sapiens 3-phosphooxypyruvate + NADH + H+
-
r

Synonyms

Synonyms Comment Organism
D-3-phosphoglycerate dehydrogenase
-
Homo sapiens
Phgdh
-
Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00166
-
pH and temperature not specified in the publication Homo sapiens ixocarpalactone A
0.0025
-
pH and temperature not specified in the publication Homo sapiens N-(4,6-dimethylpyridin-2-yl)-4-(4-(trifluoromethyl)benzyl)piperazine-1-carbothioamide
0.0098
-
pH and temperature not specified in the publication Homo sapiens azacoccone E
0.033
-
pH and temperature not specified in the publication Homo sapiens 5-[(2-furanylcarbonyl)amino]-3-methyl-4-thiocyanato-2-thiophenecarboxylic acid ethyl ester

Expression

Organism Comment Expression
Homo sapiens the enzyme is highly expressed in tumors as a result of amplification, transcription, or its degradation and stability alteration, which dysregulates the serine biosynthesis pathway via metabolic enzyme activity to nourish tumors. High expression of the enzyme is dramatically related to tumor resistance to chemotherapies up

General Information

General Information Comment Organism
drug target high expression of the enzyme (PHGDH) is dramatically related to tumor resistance to chemotherapies, and treatment with PHGDH inhibitor works synergistically with chemotherapy drugs and may be an effective approach to improve overall patient survival Homo sapiens
metabolism the first and only rate-limiting enzyme in the de novo serine biosynthetic pathway Homo sapiens
physiological function the enzyme promotes some tumors growth via non-metabolic way by upregulating target cancer-promoting genes Homo sapiens