General Information of the Protein
Protein ID
PT01881
Protein Name
Hexokinase-4
Secondarily
Protein Name
Glucokinase
Hexokinase type IV
Hexokinase-D
Gene Name
GCK
Sequence
MLDDRARMEAAKKEKVEQILAEFQLQEEDLKKVMRRMQKEMDRGLRLETHEEASVKMLPTYVRSTPEGSEVGDFLSLDLGGTNFRVMLVKVGEGEEGQWSVKTKHQMYSIPEDAMTGTAEMLFDYISECISDFLDKHQMKHKKLPLGFTFSFPVRHEDIDKGILLNWTKGFKASGAEGNNVVGLLRDAIKRRGDFEMDVVAMVNDTVATMISCYYEDHQCEVGMIVGTGCNACYMEEMQNVELVEGDEGRMCVNTEWGAFGDSGELDEFLLEYDRLVDESSANPGQQLYEKLIGGKYMGELVRLVLLRLVDENLLFHGEASEQLRTRGAFETRFVSQVESDTGDRKQIYNILSTLGLRPSTTDCDIVRRACESVSTRAAHMCSAGLAGVINRMRESRSEDVMRITVGVDGSVYKLHPSFKERFHASVRRLTPSCEITFIESEEGSGRGAALVSAVACKKACMLGQ
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
Function
Catalyzes the phosphorylation of hexose, such as D-glucose, D-fructose and D-mannose, to hexose 6-phosphate (D-glucose 6-phosphate, D-fructose 6-phosphate and D-mannose 6-phosphate, respectively) (PubMed:7742312, PubMed:11916951, PubMed:15277402, PubMed:17082186, PubMed:18322640, PubMed:19146401, PubMed:25015100, PubMed:8325892). Compared to other hexokinases, has a weak affinity for D-glucose, and is effective only when glucose is abundant (By similarity). Mainly expressed in pancreatic beta cells and the liver and constitutes a rate-limiting step in glucose metabolism in these tissues (PubMed:18322640, PubMed:25015100, PubMed:8325892, PubMed:11916951, PubMed:15277402). Since insulin secretion parallels glucose metabolism and the low glucose affinity of GCK ensures that it can change its enzymatic activity within the physiological range of glucose concentrations, GCK acts as a glucose sensor in the pancreatic beta cell (By similarity). In pancreas, plays an important role in modulating insulin secretion (By similarity). In liver, helps to facilitate the uptake and conversion of glucose by acting as an insulin-sensitive determinant of hepatic glucose usage (By similarity). Required to provide D-glucose 6-phosphate for the synthesis of glycogen (PubMed:8878425). Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate (PubMed:7742312).
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Uniprot ID
Primary ID:
P35557

Secondarily ID:
A4D2J2
A4D2J3
Q05810
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Ensembl ID
ENSG00000106633
HGNC ID
HGNC:4195
Subcellular Location
Cytoplasm
Nucleus
Mitochondrion
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000011 , CHO
Compound ID Compound Name Compound Formula
CP0846140
3-({5-[4-(Ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1Hbenzimidazol-6-yl}methyl)-1,3-oxazolidine-2,4-dione
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C24H20N4O6S
 2
1
EC50 = 20 nM
   TI
   LI
   LO
   TS
2
EC50 = 90 nM
   TI
   LI
   LO
   TS
CP0375578
1-({5-[4-(Ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1Hbenzimidazol-6-yl}methyl)pyrrolidine-2,5-dione
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C25H22N4O5S
 2
1
EC50 = 40 nM
   TI
   LI
   LO
   TS
2
EC50 = 160 nM
   TI
   LI
   LO
   TS
CP0428948
1-({5-[4-(Ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1Hbenzimidazol-6-yl}methyl)pyrrolidin-2-one
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C25H24N4O4S
 2
1
EC50 = 60 nM
   TI
   LI
   LO
   TS
2
EC50 = 350 nM
   TI
   LI
   LO
   TS
CP0428949
3-({5-[4-(Ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1Hbenzimidazol-6-yl}methyl)-1,3-oxazolidin-2-one
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C24H22N4O5S
 2
1
EC50 = 60 nM
   TI
   LI
   LO
   TS
2
EC50 = 250 nM
   TI
   LI
   LO
   TS
CP0860857
3-({5-[4-(Ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1Hbenzimidazol-6-yl}methyl)-1-methylimidazolidine-2,4-dione
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C25H23N5O5S
 2
1
EC50 = 60 nM
   TI
   LI
   LO
   TS
2
EC50 = 180 nM
   TI
   LI
   LO
   TS
CP0381151
5-(4-(ethylsulfonyl)phenoxy)-6-((1-methyl-1H-tetrazol-5-yl)methyl)-2-(pyridin-2-yl)-1H-benzo[d]imidazole
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C23H21N7O3S
 2
1
EC50 = 70 nM
   TI
   LI
   LO
   TS
2
EC50 = 410 nM
   TI
   LI
   LO
   TS
CP0470279
N-[[6-(4-ethylsulfonylphenoxy)-2-pyridin-2-yl-3H-benzimidazol-5-yl]methyl]-N-methylacetamide
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C24H24N4O4S
 2
1
EC50 = 70 nM
   TI
   LI
   LO
   TS
2
EC50 = 300 nM
   TI
   LI
   LO
   TS
CP0507293
1-({5-[4-(Ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1Hbenzimidazol-6-yl}methyl)-3-methylimidazolidin-2-one
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C25H25N5O4S
 2
1
EC50 = 80 nM
   TI
   LI
   LO
   TS
2
EC50 = 320 nM
   TI
   LI
   LO
   TS
CP0428952
6-[(1,1-Dioxidoisothiazolidin-2-yl)methyl]-5-[4-(ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1H-benzimidazole
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C24H24N4O5S2
 2
1
EC50 = 90 nM
   TI
   LI
   LO
   TS
2
EC50 = 460 nM
   TI
   LI
   LO
   TS
CP0375572
4-({5-[4-(Ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1Hbenzimidazol-6-yl}methyl)morpholin-3-one
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C25H24N4O5S
 2
1
EC50 = 100 nM
   TI
   LI
   LO
   TS
2
EC50 = 280 nM
   TI
   LI
   LO
   TS
CP0430706
N-ethyl-N-[[6-(4-ethylsulfonylphenoxy)-2-pyridin-2-yl-3H-benzimidazol-5-yl]methyl]acetamide
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C25H26N4O4S
 2
1
EC50 = 110 nM
   TI
   LI
   LO
   TS
2
EC50 = 500 nM
   TI
   LI
   LO
   TS
CP0375580
5-[4-(Ethylsulfonyl)phenoxy]-6-(1H-imidazol-1-ylmethyl)-2-(pyridin-2-yl)-1H-benzimidazole
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C24H21N5O3S
 2
1
EC50 = 120 nM
   TI
   LI
   LO
   TS
2
EC50 = 430 nM
   TI
   LI
   LO
   TS
CP0405514
3-(5-(4-(ethylsulfonyl)phenoxy)-2-(pyridin-2-yl)-1H-benzo[d]imidazol-6-yl)-N,N-dimethylpropanamide
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C25H26N4O4S
 2
1
EC50 = 120 nM
   TI
   LI
   LO
   TS
2
EC50 = 620 nM
   TI
   LI
   LO
   TS
CP0470280
N-[[6-(4-ethylsulfonylphenoxy)-2-pyridin-2-yl-3H-benzimidazol-5-yl]methyl]acetamide
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C23H22N4O4S
 2
1
EC50 = 220 nM
   TI
   LI
   LO
   TS
2
EC50 = 1410 nM
   TI
   LI
   LO
   TS
CP0375579
5-[4-(Ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-6-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
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C25H26N4O3S
 1
1
EC50 > 5000 nM
   TI
   LI
   LO
   TS
CP0428951
1-({5-[4-(Ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1Hbenzimidazol-6-yl}methyl)imidazolidin-2-one
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C24H23N5O4S
 1
1
EC50 > 5000 nM
   TI
   LI
   LO
   TS
Clinical Information about the Protein
Target 1 ( Glucokinase (GCK) )
Target Type Clinical trial Target
Disease 2 Target-related Diseases  2
1 Diabetic complication [ICD-11: 5A2Y]
2 Type-2 diabetes [ICD-11: 5A11]
Clinical Trial Drug(s) 3 Clinical Trial Drugs  3
1 AZD1656 Phase 2
Diabetic complication
2 PF-04937319 Phase 2
Type-2 diabetes
3 PF-04991532 Phase 2
Diabetic complication