Last update 01 Nov 2024

GK

Last update 01 Nov 2024

Basic Info

Synonyms

ATP:glycerol 3-phosphotransferase, GK, GK1

+ [3]

Introduction

Key enzyme in the regulation of glycerol uptake and metabolism.

Drugs associated with GK

AMG-1694

Target

GK x GKRP

Mechanism

GK modulators [+1]

Active Org.-

Originator Org.

Amgen, Inc.

Active Indication-

Inactive Indication

Diabetes Mellitus

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

AMG-3969

Target

GK x GKRP

Mechanism

GK modulators [+1]

Active Org.-

Originator Org.

Nanjing Anjin Pharmaceutical Co., Ltd.

Active Indication-

Inactive Indication

Diabetes Mellitus

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GK

100 Translational Medicine associated with GK

0 Patents (Medical) associated with GK

2,714

Literatures (Medical) associated with GK

30 Sep 2024·Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Molecular Docking, Pharmacophore Modeling, and ADMET Prediction of Novel Heterocyclic Leads as Glucokinase Activators

Article

Author: Mehra, Anuradha ; Mittal, Amit ; Singh, Shivangi

aims:To address type 2 diabetes, as well as minimize unwanted side effects, this research endeavor aimed to develop activators of glucokinase.background:A pivotal impetus has driven the development of numerous small molecules aiming to improve therapeutic strategies for type 2 diabetes. Glucokinase (GK) activation has been offered a new realm of therapeutic antidiabetic activity with novel heterocyclic derivatives. In the context of antidiabetic drug design, GK is an interesting and newly validated target. A key enzyme needed for blood glucose homeostasis is Glucokinase, which is dysfunctional in individuals with type 2 diabetes. Heterocyclic derivatives are utilized in this innovative approach to activate GK enzymes as medicinal agents that will significantly improve type 2 diabetes management.objective:To address type 2 diabetes, as well as minimize unwanted side effects, this research endeavor aimed to develop activators of glucokinase.method:A rigorous scrutiny was conducted of the Maybridge online repository which houses a formidable collection of 53,000 lead compounds. A collection of 125 compounds that contain the thiazolidinedione core was selected from this extensive collection. The structures were generated using Chemdraw 2D, stabilize conformation with ChemBioDraw Ultra and docked using Auto Dock Vina 1.5.6 in this this methodology. In addition, log P was predicted online using the Swiss ADME algorithm. The PKCSM software was used to predict the toxicity of the leading compounds.result:The highest binding affinity was found for AS72 and AS108 to GK receptors. GI absorption and excretion of these compounds are efficient due to Lipinski Rule of Five compliance. When compared with the standard drugs Dorzagliatin (GKA) and MRK (co-crystallized ligand), these substances demonstrate a notable lack of AMES toxicity, skin sensitization, and hepatotoxicity.conclusion:In recent studies, lead molecules that possess enhanced pharmacokinetic profiles, increased binding affinity, and lower toxicity were developed to act as glucokinase activators.other:-

21 Sep 2024·International journal of molecular sciences

Exploring the Kinetics and Thermodynamics of a Novel Histidine Ammonia-Lyase from Geobacillus kaustophilus.

Article

Author: Las Heras-Vázquez, Francisco Javier ; Clemente-Jiménez, Josefa María ; Salas-Garrucho, Francisco Manuel ; Contreras, Lellys M ; Rodríguez-Vico, Felipe ; Carrillo-Moreno, Alba

Histidine ammonia-lyase (HAL) plays a pivotal role in the non-oxidative deamination of L-histidine to produce trans-urocanic, a crucial process in amino acid metabolism. This study examines the cloning, purification, and biochemical characterization of a novel HAL from Geobacillus kaustophilus (GkHAL) and eight active site mutants to assess their effects on substrate binding, catalysis, thermostability, and secondary structure. The GkHAL enzyme was successfully overexpressed and purified to homogeneity. Its primary sequence displayed 40.7% to 43.7% similarity with other known HALs and shared the same oligomeric structure in solution. Kinetic assays showed that GkHAL has optimal activity at 85 °C and pH 8.5, with high thermal stability even after preincubation at high temperatures. Mutations at Y52, H82, N194, and E411 resulted in a complete loss of catalytic activity, underscoring their essential role in enzyme function, while mutations at residues Q274, R280, and F325 did not abolish activity but did reduce catalytic efficiency. Notably, mutants R280K and F325Y displayed novel activity with L-histidinamide, expanding the substrate specificity of HAL enzymes. Circular dichroism (CD) analysis showed minor secondary structure changes in the mutants but no significant effect on global GkHAL folding. These findings suggest that GkHAL could be a promising candidate for potential biotechnological applications.

01 Sep 2024·Acta Pharmaceutica Sinica B

Glycodiversification of gentamicins through in vivo glycosyltransferase swapping enabled the creation of novel hybrid aminoglycoside antibiotics with potent activity and low ototoxicity

Article

Author: Jian, Xinyun ; Wang, Cheng ; Wu, Shijuan ; Leadlay, Peter F ; Zhou, Fuling ; Huang, Chuan ; Liu, Dong ; Deng, Zixin ; Sun, Guo ; Sun, Yuhui ; Qiu, Chengbing ; Liu, Yuanzheng

Aminoglycosides (AGs) are a class of antibiotics with a broad spectrum of activity. However, their use is limited by safety concerns associated with nephrotoxicity and ototoxicity, as well as drug resistance. To address these issues, semi-synthetic approaches for modifying natural AGs have generated new generations of AGs, however, with limited types of modification due to significant challenges in synthesis. This study explores a novel approach that harness the bacterial biosynthetic machinery of gentamicins and kanamycins to create hybrid AGs. This was achieved by glycodiversification of gentamicins via swapping the glycosyltransferase (GT) in their producer with the GT from kanamycins biosynthetic pathway and resulted in the creation of a series of novel AGs, therefore referred to as genkamicins (GKs). The manipulation of the hybrid biosynthetic pathway enabled the targeted accumulation of different GK species and the isolation and characterization of six GK components. These compounds display retained antimicrobial activity against a panel of World Health Organization (WHO) critical priority pathogens, and GK-C2a, in particular, demonstrates low ototoxicity compared to clinical drugs in zebrafish embryos. This study provides a new strategy for diversifying the structure of AGs and a potential avenue for developing less toxic AG drugs to combat infectious diseases.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

GK

Basic Info

Related

Analysis