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Updated: Jul 11, 2025

A Semi-Quantitative Drug Affinity Responsive Target Stability DARTS assay for studying Rapamycin/mTOR interaction
Published on: August 27, 2019
Optimization of mTOR Inhibitors Using Property-Based Drug Design and Free-Wilson Analysis for Improved In Vivo
Sean T Murphy1, Joy Atienza1, Jason W Brown1
1Takeda California, 9625 Towne Centre Drive, San Diego, California 92121, United States.
Abstract:
The mTOR kinase regulates a variety of critical cellular processes and has become a target for the treatment of various cancers. Using a combination of property-based drug design and Free-Wilson analysis, we further optimized a series of selective mTOR inhibitors based on the (S)-6a-methyl-6a,7,9,10-tetrahydro[1,4]oxazino[3,4-h]pteridin-6(5H)-one scaffold. Our efforts resulted in 14c, which showed similar in vivo efficacy compared to previous lead 1 at 1/15 the dose, a result of its improved drug-like properties.
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