Related Experiment Video

Updated: Apr 4, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

11.9K

In vitro inhibition of AKR1Cs by sulphonylureas and the structural basis

Yining Zhao1, Xuehua Zheng1, Hong Zhang1

  • 1School of Pharmaceutical Sciences & Centre for Cellular and Structural Biology of Sun Yat-sen University, Guangzhou 510006, China.

Chemico-Biological Interactions
|September 13, 2015
PubMed

Insights

Sulfonylureas, used for type II diabetes, show varied effects on cancer progression by inhibiting aldo-keto reductases (AKR1Cs). These enzymes are linked to hormone-related cancers, and drug interactions were studied using X-ray crystallography.

Area of Science:

  • Biochemistry
  • Oncology
  • Endocrinology

Background:

  • Conflicting epidemiological data exist on sulfonylureas' impact on cancer progression in type II diabetes patients.
  • The precise mechanisms by which sulfonylureas influence tumor growth remain unclear.

Purpose of the Study:

  • To investigate the in vitro inhibitory effects of seven sulfonylureas on AKR1C enzymes.
  • To analyze the interactions between sulfonylureas and AKR1Cs using X-ray crystallography.

Main Methods:

  • In vitro enzyme inhibition assays were performed for seven sulfonylureas against AKR1C1, AKR1C2, and AKR1C3.
  • X-ray crystallography was employed to visualize and analyze the binding interactions of sulfonylureas with AKR1Cs.

Main Results:

  • Seven sulfonylureas demonstrated differential in vitro inhibition of AKR1C enzymes.
  • X-ray crystallography provided insights into the specific interactions between tested sulfonylureas and AKR1C enzymes.

Conclusions:

  • Sulfonylureas exhibit varied inhibitory profiles against AKR1C enzymes, suggesting potential differential roles in cancer progression.
  • Understanding these interactions is crucial for evaluating the oncological risks or benefits of sulfonylureas in diabetic patients.
Keywords:
AKR1CsCrystal structuresInhibitionSelectivitySulphonylureas

More Related Videos

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

15.3K
Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists10:51

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

13.2K

Related Concept Videos

Oral Hypoglycemic Agents: Sulfonylureas01:17

Oral Hypoglycemic Agents: Sulfonylureas

Sulfonylureas are oral hypoglycemic agents utilized in treating type 2 diabetes. They are characterized by their unique sulfonylurea chemical structure. The family of sulfonylureas is divided into generations. First-generation sulfonylureas, including tolbutamide (Orinase), chlorpropamide (Diabinese), and tolazamide (Tolinase), trigger insulin release from pancreatic β cells and enhance peripheral tissues' insulin sensitivity. The second-generation members, such as glipizide...
1.7K
Oral Hypoglycemic Agents: Glinides01:06

Oral Hypoglycemic Agents: Glinides

Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
958
Structure-Activity Relationships and Drug Design01:28

Structure-Activity Relationships and Drug Design

Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
2.1K
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
6.9K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.2K
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

5.7K