Related Experiment Video

Updated: May 24, 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

Small-molecule ATP-competitive dual IGF-1R and insulin receptor inhibitors: structural insights, chemical diversity

Meizhong Jin1, Jing Wang, Elizabeth Buck

  • 1OSI Pharmaceuticals LLC, Farmingdale, NY 11735, USA.

Future Medicinal Chemistry
|March 8, 2012
PubMed

Insights

Targeting both insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (IR) with dual inhibitors offers enhanced cancer therapy. This review details small-molecule dual inhibitors, focusing on their binding interactions and selectivity.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Insulin-like growth factor-1 receptor (IGF-1R) is a key target in cancer drug discovery.
  • Preclinical data show IGF-1R's significant role in tumorigenesis.
  • Compensatory crosstalk between IGF-1R and insulin receptor (IR) signaling pathways is increasingly recognized.

Purpose of the Study:

  • To review recent developments in small-molecule dual IGF-1R and IR inhibitors.
  • To focus on the binding modes and interactions of these inhibitors.
  • To discuss the selectivity profiles of dual inhibitors in kinase inhibitor drug discovery.

Main Methods:

  • Literature review of preclinical data and recent research.
  • Analysis of binding modes and interactions with IGF-1R and IR.
  • Evaluation of selectivity profiles for dual kinase inhibitors.

Main Results:

  • Discovery of various small-molecule dual IGF-1R and IR inhibitors.
  • Detailed understanding of inhibitor binding to IGF-1R and/or IR.
  • Discussion on the importance of selectivity in developing effective kinase inhibitors.

Conclusions:

  • Dual targeting of IGF-1R and IR presents a more therapeutically beneficial strategy than single-target approaches.
  • Small-molecule dual inhibitors offer a promising avenue for cancer therapy.
  • Optimizing selectivity is a critical challenge and focus in developing these dual inhibitors.

More Related Videos

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

Related Concept Videos

Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but this inhibition is released...
G Protein-coupled Receptors01:15

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
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 its...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...