Target Information
Target General Infomation | |||||
---|---|---|---|---|---|
Target ID |
T87166
|
||||
Former ID |
TTDC00141
|
||||
Target Name |
Glucokinase
|
||||
Gene Name |
GCK
|
||||
Synonyms |
HK IV; HK4; Hexokinase D; Hexokinase type IV; GCK
|
||||
Target Type |
Clinical Trial
|
||||
Disease | Diabetes [ICD9: 253.5, 588.1; ICD10: E23.2, N25.1] | ||||
Non-insulin dependent diabetes [ICD10: E11.9] | |||||
Obesity; Diabetes [ICD9: 250, 278; ICD10: E08-E13, E66] | |||||
Type 2 diabetes [ICD9: 250; ICD10: E11] | |||||
Unspecified [ICD code not available] | |||||
Function |
Catalyzes the initial step in utilization of glucose by the beta-cell and liver at physiological glucose concentration. Glucokinase has a high Km for glucose, and so it is effective only when glucose is abundant. The role of GCK is to provide G6P for the synthesis of glycogen. Pancreatic glucokinase plays an important role in modulating insulin secretion. Hepatic glucokinase helps to facilitate the uptake and conversion of glucose by acting asan insulin-sensitive determinant of hepatic glucose usage.
|
||||
BioChemical Class |
Kinase
|
||||
Target Validation |
T87166
|
||||
UniProt ID | |||||
EC Number |
EC 2.7.1.2
|
||||
Sequence |
MLDDRARMEAAKKEKVEQILAEFQLQEEDLKKVMRRMQKEMDRGLRLETHEEASVKMLPT
YVRSTPEGSEVGDFLSLDLGGTNFRVMLVKVGEGEEGQWSVKTKHQMYSIPEDAMTGTAE MLFDYISECISDFLDKHQMKHKKLPLGFTFSFPVRHEDIDKGILLNWTKGFKASGAEGNN VVGLLRDAIKRRGDFEMDVVAMVNDTVATMISCYYEDHQCEVGMIVGTGCNACYMEEMQN VELVEGDEGRMCVNTEWGAFGDSGELDEFLLEYDRLVDESSANPGQQLYEKLIGGKYMGE LVRLVLLRLVDENLLFHGEASEQLRTRGAFETRFVSQVESDTGDRKQIYNILSTLGLRPS TTDCDIVRRACESVSTRAAHMCSAGLAGVINRMRESRSEDVMRITVGVDGSVYKLHPSFK ERFHASVRRLTPSCEITFIESEEGSGRGAALVSAVACKKACMLGQ |
||||
Drugs and Mode of Action | |||||
Drug(s) | AMG 151 | Drug Info | Phase 2 | Type 2 diabetes | [523678] |
AZD1656 | Drug Info | Phase 2 | Diabetes | [523091], [542677] | |
GK1-399 | Drug Info | Phase 2 | Diabetes | [525135] | |
LY-2599506 | Drug Info | Phase 2 | Diabetes | [522877] | |
LY-2608204 | Drug Info | Phase 2 | Type 2 diabetes | [523573] | |
PF-04937319 | Drug Info | Phase 2 | Type 2 diabetes | [523774] | |
PF-04991532 | Drug Info | Phase 2 | Diabetes | [523436] | |
ADV-1002401 | Drug Info | Phase 1 | Type 2 diabetes | [549053] | |
AZD5658 | Drug Info | Phase 1 | Obesity; Diabetes | [550290] | |
BMS-820132 | Drug Info | Phase 1 | Type 2 diabetes | [523348] | |
DS-7309 | Drug Info | Phase 1 | Diabetes | [524456] | |
TAK-329 | Drug Info | Phase 1 | Diabetes | [523386] | |
TTP-547 | Drug Info | Phase 1 | Diabetes | [551801] | |
ZYGK-1 | Drug Info | Phase 1 | Diabetes | [523690] | |
AZD6370 | Drug Info | Discontinued in Phase 2 | Type 2 diabetes | [548122] | |
TTP-355 | Drug Info | Discontinued in Phase 2 | Diabetes | [548396] | |
AZD-6714 | Drug Info | Discontinued in Phase 1 | Type 2 diabetes | [522643] | |
Inhibitor | ADV-1002401 | Drug Info | [544410] | ||
AMG 151 | Drug Info | [551195] | |||
Beta-D-Glucose | Drug Info | [551393] | |||
BMS-820132 | Drug Info | [533272] | |||
DS-7309 | Drug Info | [551209] | |||
GK1-399 | Drug Info | [550110] | |||
LY-2599506 | Drug Info | [551195] | |||
TAK-329 | Drug Info | [551984] | |||
Stimulator | AZD-6714 | Drug Info | [551194] | ||
Activator | AZD1656 | Drug Info | [550288] | ||
AZD5658 | Drug Info | [550290] | |||
AZD6370 | Drug Info | [550288] | |||
GKA-23 | Drug Info | [543714] | |||
GKA1 | Drug Info | [535916] | |||
LY-2608204 | Drug Info | [551101] | |||
PF-04991532 | Drug Info | [532788], [533022] | |||
PSN-101 | Drug Info | [550543] | |||
SKL-19014 | Drug Info | [543714] | |||
TTP-355 | Drug Info | [548397] | |||
TTP-547 | Drug Info | [543714] | |||
ZYGK-1 | Drug Info | [543714] | |||
Modulator | PF-04937319 | Drug Info | [533212] | ||
Piragliatin | Drug Info | ||||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | Glycolysis / Gluconeogenesis | ||||
Galactose metabolism | |||||
Starch and sucrose metabolism | |||||
Amino sugar and nucleotide sugar metabolism | |||||
Butirosin and neomycin biosynthesis | |||||
Metabolic pathways | |||||
Biosynthesis of antibiotics | |||||
Carbon metabolism | |||||
Insulin signaling pathway | |||||
Insulin secretion | |||||
Prolactin signaling pathway | |||||
Glucagon signaling pathway | |||||
Type II diabetes mellitus | |||||
Maturity onset diabetes of the young | |||||
Central carbon metabolism in cancer | |||||
Pathway Interaction Database | FOXA2 and FOXA3 transcription factor networks | ||||
HIF-1-alpha transcription factor network | |||||
PathWhiz Pathway | Nucleotide Sugars Metabolism | ||||
Starch and Sucrose Metabolism | |||||
Galactose Metabolism | |||||
Trehalose Degradation | |||||
Reactome | Regulation of gene expression in beta cells | ||||
Glucose transport | |||||
Glycolysis | |||||
WikiPathways | SIDS Susceptibility Pathways | ||||
Glycolysis and Gluconeogenesis | |||||
MAPK Signaling Pathway | |||||
Regulation of beta-cell development | |||||
Metabolism of carbohydrates | |||||
Hexose transport | |||||
References | |||||
Ref 522643 | ClinicalTrials.gov (NCT00886366) Single Ascending Dose Study With Healthy Male Volunteers and Type II Diabetic Patients. U.S. National Institutes of Health. | ||||
Ref 522877 | ClinicalTrials.gov (NCT01024244) A Study of LY2599506 in Patients With Type 2 Diabetes. U.S. National Institutes of Health. | ||||
Ref 523091 | ClinicalTrials.gov (NCT01152385) Japan Dose Regimen Study of AZD1656 in Japanese Type 2 Diabetes Mellitus Patients. U.S. National Institutes of Health. | ||||
Ref 523348 | ClinicalTrials.gov (NCT01290575) Multiple Ascending Dose Study of BMS-820132 in Patients With Type 2 Diabetes. U.S. National Institutes of Health. | ||||
Ref 523386 | ClinicalTrials.gov (NCT01311076) TAK-329 Glucose Clamp Study. U.S. National Institutes of Health. | ||||
Ref 523436 | ClinicalTrials.gov (NCT01338870) Study of Safety and Efficacy of PF-04991532 in Subjects With Type 2 Diabetes. U.S. National Institutes of Health. | ||||
Ref 523573 | ClinicalTrials.gov (NCT01408095) A Study in Patients With Type 2 Diabetes. U.S. National Institutes of Health. | ||||
Ref 523678 | ClinicalTrials.gov (NCT01464437) AMG 151 Amgen Protocol Number 20100761. U.S. National Institutes of Health. | ||||
Ref 523690 | ClinicalTrials.gov (NCT01472809) A Clinical Study to Evaluate Safety, Tolerability and Pharmacokinetics of Oral ZYGK1 in Healthy Volunteers. U.S. National Institutes of Health. | ||||
Ref 523774 | ClinicalTrials.gov (NCT01517373) Study To Understand Efficacy And Safety Of Investigational Agent (PF-04937319) Compared To Approved Agent (Glimepiride) In Patients With Diabetes On Metformin. U.S. National Institutes of Health. | ||||
Ref 524456 | ClinicalTrials.gov (NCT01956305) Randomized, Placebo-controlled, 2 Period, Single-blind, Sequential, Multiple Ascending Dose Study. U.S. National Institutes of Health. | ||||
Ref 525135 | ClinicalTrials.gov (NCT02405260) Add Glucokinase Activator to Target A1c. U.S. National Institutes of Health. | ||||
Ref 542677 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7701). | ||||
Ref 548122 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022135) | ||||
Ref 548396 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025266) | ||||
Ref 532788 | The hepatoselective glucokinase activator PF-04991532 ameliorates hyperglycemia without causing hepatic steatosis in diabetic rats. PLoS One. 2014 May 23;9(5):e97139. | ||||
Ref 533022 | Comparison of the circulating metabolite profile of PF-04991532, a hepatoselective glucokinase activator, across preclinical species and humans: potential implications in metabolites in safety testing assessment. Drug Metab Dispos. 2015 Feb;43(2):190-8. | ||||
Ref 533212 | Two dose-ranging studies with PF-04937319, a systemic partial activator of glucokinase, as add-on therapy to metformin in adults with type 2 diabetes. Diabetes Obes Metab. 2015 Aug;17(8):751-9. | ||||
Ref 533272 | Utilization of the Zucker Diabetic Fatty (ZDF) Rat Model for Investigating Hypoglycemia-related Toxicities. Toxicol Pathol. 2015 Aug;43(6):825-37. | ||||
Ref 535916 | Stimulation of hepatocyte glucose metabolism by novel small molecule glucokinase activators. Diabetes. 2004 Mar;53(3):535-41. | ||||
Ref 543714 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2798). | ||||
Ref 544410 | The Hepatoselective Glucokinase Activator PF-04991532 Ameliorates Hyperglycemia without Causing Hepatic Steatosis in Diabetic Rats. PLoS One. 2014; 9(5): e97139. | ||||
Ref 548397 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025266) | ||||
Ref 550110 | Clinical pipeline report, company report or official report of vTv Therapeutics, NCT02405260. |
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.