Related Experiment Video
Updated: Feb 8, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Evolution strategy of ROS1 kinase inhibitors for use in cancer therapy
Siming Liu1, Haikui Yang1, Ying Jiang1
1Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
Abstract:
The abnormal expression of c-ros oncogene1 receptor tyrosine kinase (ROS1) has been identified as clinically actionable oncogenic driver in non-small-cell lung cancer. Since crizotinib was approved by the US FDA for the treatment of advanced ROS1-positive non-small-cell lung cancer, ROS1 kinase has become a promising therapeutic target. Under the guidance of some advanced computer-assisted technologies, such as structure-based drug design, homology modeling and lipophilic efficiency parameters, several potent and selective inhibitors against wild-type and mutant ROS1 were designed and synthesized. In this article, we will review a series of scaffolds targeting ROS1 kinase from the hit-to-drug evolution strategies of their representative compounds and it is hoped that these design strategies would facilitate medicinal chemists to optimize the process of drug design.
Insights
Abnormal ROS1 (c-ros oncogene1 receptor tyrosine kinase) expression drives non-small-cell lung cancer. Computer-aided design yielded potent ROS1 inhibitors, aiding drug development for this target.
Area of Science:
- Medicinal Chemistry
- Oncology
- Pharmacology
Background:
- Abnormal expression of c-ros oncogene1 receptor tyrosine kinase (ROS1) is a key driver in non-small-cell lung cancer (NSCLC).
- ROS1-positive NSCLC is a target for therapies like crizotinib, highlighting ROS1 kinase as a significant therapeutic target.
Purpose of the Study:
- To review scaffold evolution strategies for developing potent and selective ROS1 kinase inhibitors.
- To explore the application of advanced computer-assisted technologies in drug design against ROS1.
Main Methods:
- Utilized structure-based drug design principles.
- Employed homology modeling techniques.
- Applied lipophilic efficiency (LiP) parameters for inhibitor optimization.
Main Results:
- Successfully designed and synthesized several potent and selective inhibitors targeting both wild-type and mutant ROS1.
- Demonstrated the efficacy of hit-to-drug evolution strategies for representative compounds.
Conclusions:
- Advanced computational approaches facilitate the design of effective ROS1 kinase inhibitors.
- These design strategies can significantly aid medicinal chemists in optimizing drug discovery processes for ROS1-targeted therapies.
Related Concept Videos
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:55The Evidence for Evolution
01:54Convergent Evolution
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:54Protein Kinases and Phosphatases
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
01:26Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
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...