Related Experiment Video

Updated: Feb 6, 2026

Protein Kinase C-delta Inhibitor Peptide Formulation using Gold Nanoparticles
06:06

Protein Kinase C-delta Inhibitor Peptide Formulation using Gold Nanoparticles

Published on: March 9, 2019

5.9K

Structure-guided design of a potent peptide inhibitor targeting the interaction between CRK and ABL kinase

Qingliang Shen1, Veer S Bhatt1, Inna Krieger1

  • 1Department of Biochemistry and Biophysics , Texas A&M University , College Station , Texas , USA .

Medchemcomm
|August 16, 2018
PubMed

Insights

A new peptide inhibitor, PRM-3, effectively blocks the interaction between CRK proteins and ABL kinase, offering a promising strategy against cancer metastasis and drug resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • CT-10 regulator of kinase (CRK) proteins are implicated in cancer metastasis.
  • CRK proteins are key substrates for ABL and BCR-ABL kinases, crucial in chronic myeloid leukemia.
  • Inhibiting CRK-BCR-ABL interaction is a potential therapeutic strategy for cancer.

Purpose of the Study:

  • To develop a peptide inhibitor targeting the CRK-II and ABL kinase interaction.
  • To evaluate the efficacy of the peptide inhibitor PRM-3 against ABL and BCR-ABL kinases.

Main Methods:

  • Development of a peptide inhibitor, PRM-3.
  • Biochemical assays to assess binding affinity and inhibitory activity.
  • Testing PRM-3 against wild-type ABL and drug-resistant T315I-ABL kinase.

Main Results:

  • PRM-3 binds to the CRK-II nSH3 domain with high affinity (10 nM).
  • PRM-3 inhibits ABL-dependent CRK-II phosphorylation more effectively than imatinib.
  • PRM-3 demonstrates efficacy against the drug-resistant T315I-ABL kinase.

Conclusions:

  • PRM-3 is a potent inhibitor of CRK-II and ABL kinase interaction.
  • PRM-3 offers a potential therapeutic approach to overcome ABL kinase drug resistance in cancer.
  • This study presents a novel strategy against cancers driven by ABL kinase activity.

More Related Videos

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors10:33

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

11.8K
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia10:49

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Published on: September 18, 2013

18.7K

Related Concept Videos

Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.2K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

4.5K
Peptide Bonds02:43

Peptide Bonds

A peptide bond covalently attaches amino acids through a dehydration reaction. One amino acid's carboxyl group and another amino acid's amino group combine, releasing a water molecule. The resulting bond is the peptide bond. The products that such linkages form are peptides. As more amino acids join this growing chain, the resulting chain is a polypeptide. Each polypeptide has a free amino group at one end. This end has the N-terminal, or the amino-terminal, and the other end has a free...
83.2K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.0K
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...
1.8K
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers01:26

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers

Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
550