PMID- 32286938
OWN - NLM
STAT- MEDLINE
DCOM- 20201222
LR  - 20201222
IS  - 1873-4286 (Electronic)
IS  - 1381-6128 (Linking)
VI  - 26
IP  - 21
DP  - 2020
TI  - Recent Developments in Medicinal Chemistry of Allosteric Activators of Human 
      Glucokinase for Type 2 Diabetes Mellitus Therapeutics.
PG  - 2510-2552
LID - 10.2174/1381612826666200414163148 [doi]
AB  - BACKGROUND: Glucokinase (GK), a cytoplasmic enzyme catalyzes the metabolism of 
      glucose to glucose- 6-phosphate with the help of ATP and aids in the controlling 
      of blood glucose levels within the normal range in humans. In pancreatic beta-cells, 
      it plays a chief role by controlling the glucose-stimulated secretion of insulin 
      and in liver hepatocyte cells, it controls the metabolism of carbohydrates. GK 
      acts as a promising drug target for the pharmacological treatment of patients 
      with type 2 diabetes mellitus (T2DM) as it plays an important role in the control 
      of carbohydrate metabolism. METHODS: Data used for this review was based on the 
      search from several science databases as well as various patent databases. The 
      main data search terms used were allosteric GK activators, diabetes mellitus, 
      type 2 diabetes, glucokinase, glucokinase activators and human glucokinase. 
      RESULTS: This article discusses an overview of T2DM, the biology of GK, the role 
      of GK in T2DM, recent updates in the development of small molecule GK activators 
      reported in recent literature, mechanism of action of GK activators and their 
      clinical status. CONCLUSION: GK activators are the novel class of pharmacological 
      agents that enhance the catalytic activity of GK enzyme and display their 
      antihyperglycemic effects. Broad diversity of chemical entities including 
      benzamide analogues, carboxamides, acrylamides, benzimidazoles, quinazolines, 
      thiazoles, pyrimidines, pyridines, orotic acid amides, amino acid derivatives, 
      amino phosphates and urea derivatives have been synthesized in past two decades 
      as potent allosteric activators of GK. Presently, the pharmaceutical companies 
      and researchers are focusing on the design and development of liver-selective GK 
      activators for preventing the possible adverse effects associated with GK 
      activators for the long-term treatment of T2DM.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.net.
FAU - Grewal, Ajmer S
AU  - Grewal AS
AD  - Chitkara College of Pharmacy, Chitkara University, Punjab, India.
FAU - Lather, Viney
AU  - Lather V
AD  - Amity Institute of Pharmacy, Amity University, Noida, Uttar Pradesh, India.
FAU - Charaya, Neha
AU  - Charaya N
AD  - Jan Nayak Ch. Devi Lal Memorial College of Pharmacy, Haryana, India.
FAU - Sharma, Neelam
AU  - Sharma N
AD  - Chitkara College of Pharmacy, Chitkara University, Punjab, India.
FAU - Singh, Sukhbir
AU  - Singh S
AD  - Chitkara College of Pharmacy, Chitkara University, Punjab, India.
FAU - Kairys, Visvaldas
AU  - Kairys V
AD  - Department of Bioinformatics, Institute of Biotechnology, Vilnius University, 
      Vilnius, Lithuania.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Curr Pharm Des
JT  - Current pharmaceutical design
JID - 9602487
RN  - 0 (Enzyme Activators)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - EC 2.7.1.2 (Glucokinase)
SB  - IM
MH  - Chemistry, Pharmaceutical
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Enzyme Activators/pharmacology
MH  - *Glucokinase
MH  - Humans
MH  - Hypoglycemic Agents/pharmacology
MH  - Insulin
OTO - NOTNLM
OT  - Allosteric
OT  - GK activators
OT  - Glucokinase (GK)
OT  - antidiabetic
OT  - diabetes mellitus
OT  - type 2 diabetes mellitus.
EDAT- 2020/04/15 06:00
MHDA- 2020/12/23 06:00
CRDT- 2020/04/15 06:00
PHST- 2019/11/10 00:00 [received]
PHST- 2020/04/07 00:00 [accepted]
PHST- 2020/04/15 06:00 [pubmed]
PHST- 2020/12/23 06:00 [medline]
PHST- 2020/04/15 06:00 [entrez]
AID - CPD-EPUB-105815 [pii]
AID - 10.2174/1381612826666200414163148 [doi]
PST - ppublish
SO  - Curr Pharm Des. 2020;26(21):2510-2552. doi: 10.2174/1381612826666200414163148.