Related Experiment Video

Updated: May 14, 2026

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

Recent advancements in small molecule inhibitors of insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase as

Arvind Negi1, P Ramarao, Raj Kumar

  • 1Laboratory for Drug Design and Synthesis, Centre for Chemical and Pharmaceutical Sciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda 151 001, India.

Mini Reviews in Medicinal Chemistry
|February 5, 2013
PubMed

Insights

Targeting the insulin-like growth factor 1 receptor (IGF-1R) with small molecules offers a promising, cost-effective approach for cancer chemotherapy. This review highlights recent discoveries and binding interactions of small molecules targeting IGF-1R.

Area of Science:

  • Oncology
  • Biochemistry
  • Pharmacology

Background:

  • Cancer chemotherapy is shifting towards targeted therapies, with protein tyrosine kinases (PTKs) as key targets.
  • Insulin receptors (IRs), insulin-like growth factor 1 receptors (IGF-1R), and their hybrids are PTKs that promote cancer cell growth and survival.
  • Inhibiting the IGF-1R signaling pathway is a crucial strategy in cancer treatment.

Purpose of the Study:

  • To provide an overview of small molecule inhibitors targeting IGF-1R.
  • To discuss recent discoveries, structure-activity relationship (SAR) studies, and binding interactions of these inhibitors.
  • To highlight the advantages of small molecule inhibitors over other therapeutic strategies.

Main Methods:

  • Review of existing literature on IGF-1R inhibitors.
  • Analysis of SAR studies for small molecule compounds.
  • Examination of binding interactions with IGF-1R active and allosteric sites.

Main Results:

  • Small molecules targeting IGF-1R have gained attention due to favorable ADMET properties, oral bioavailability, and cost-effectiveness.
  • Various strategies have been explored to inhibit IGF-1R signaling, including antibodies and antisense approaches.
  • Small molecules offer advantages in terms of synthesis, optimization, and reduced side effects compared to other modalities.

Conclusions:

  • Small molecule inhibitors represent a significant advancement in targeting IGF-1R for cancer therapy.
  • Further research into SAR and binding interactions will facilitate the development of more effective IGF-1R-targeted drugs.
  • Targeting IGF-1R with small molecules holds promise for improved cancer treatment outcomes.

Related Concept Videos

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...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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:
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...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
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...