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An updated patent review of small-molecule ROS1 kinase inhibitors (2015-2021)
Meng Liu1, Jintian Dai1, Mudan Wei1
1Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang, Jiangxi China.
Introduction:
C-ros oncogene 1 (ROS1) is the sole member of the ROS1 receptor tyrosine kinase (ROS1-RTK) family, which is involved in the formation of non-small cell lung cancer (NSCLC), gastric adenocarcinoma, colorectal cancer, and other malignant tumors. At present, only crizotinib was approved for the treatment of advanced ROS1-positive NSCLC, and there have been reports of ROS1 mutations resulting in drug resistance. Consequently, it is necessary to develop new generations of inhibitors to overcome the existing problems.
Areas Covered:
This review summarizes the inhibitors with ROS1 inhibitory activity which are undergoing clinical trials and recent advances in patented ROS1 small molecular inhibitors from 2015 to 2021.
Expert Opinion:
ROS1 rearrangements have been found in approximately 1%-2% of patients with NSCLC. Since the approval of crizotinib as multi-targeted ALK/MET/ROS1 kinase inhibitor for ALK-mutated NSCLC therapy, the researchers are focusing on ROS1-mutated tumors, especially NSCLC. However, drug-resistant mutations have already been found in clinical application. Therefore, it is still urgent to develop new generation of ROS1 inhibitors.
Insights
New ROS1 inhibitors are crucial for treating non-small cell lung cancer (NSCLC) due to drug resistance. This review covers recent advances in patented ROS1 inhibitors and those in clinical trials.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- C-ros oncogene 1 (ROS1) receptor tyrosine kinase (ROS1-RTK) is implicated in various cancers, including non-small cell lung cancer (NSCLC).
- ROS1 rearrangements occur in 1-2% of NSCLC patients.
- Crizotinib is the only approved ROS1 inhibitor, but drug resistance is a growing concern.
Purpose of the Study:
- To review inhibitors with ROS1 inhibitory activity currently in clinical trials.
- To summarize recent advancements in patented ROS1 small molecular inhibitors from 2015 to 2021.
Main Methods:
- Literature review of clinical trials involving ROS1 inhibitors.
- Analysis of patented small molecular ROS1 inhibitors published between 2015 and 2021.
Main Results:
- Identified several ROS1 inhibitors in various phases of clinical trials.
- Detailed recent patented small molecular inhibitors targeting ROS1, highlighting their chemical structures and mechanisms.
Conclusions:
- There is an urgent need for novel ROS1 inhibitors to overcome drug resistance in ROS1-positive NSCLC.
- Ongoing research and development are crucial for advancing ROS1-targeted therapies.
