mTOR kinase is a highly conserved central regulator of cell growth and metabolism, and a key cancer drug target. Numerous mTOR kinase inhibitors have been developed but have not been approved by FDA. A new screening tool for mTOR kinase inhibitors will facilitate mTOR therapeutic development and related pharmacology studies.
Rutgers scientists have developed a novel humanized yeast model by engineering a yeast TOR2 kinase-human TOR kinase (yTOR2-mTOR) fusion. TOR2-mTOR fusion genes are expressed in the tor2-dg strain whose growth is dependent on an active mTOR kinase, indicating that mTOR kinase domain complements the essential function of TOR2 kinase in yeast. This humanized yeast strain is sensitive to mTOR inhibitors. A series of derivatives of this yeast system has been also generated with inactive mTOR kinase or drug-resistant mutations in mTOR kinase.
- Discovery of new inhibitors for wildtype mTOR kinase or drug-resistant mutant mTOR kinase
- Evaluation of new mTOR kinase inhibitors
- Pharmacological analysis of mTOR kinase inhibitors
- Companion cancer cell lines available that carry wild type and drug-resistant mutant mTOR generated by Crispr/Cas9 knockin
- In vitro mTOR kinase inhibitors screening
- Profiling of drug-resistant mutations
- Potential to be developed into high-throughput screening systems
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