655225-01-7Relevant articles and documents
METHODS FOR DELAYING, PREVENTING, AND TREATING ACQUIRED RESISTANCE TO RAS INHIBITORS
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, (2022/01/04)
The present disclosure relates to compositions and methods for the treatment of diseases or disorders (e.g., cancer) with bi-steric inhibitors of mTOR in combination with RAS inhibitors. Specifically, in some embodiments this disclosure includes compositions and methods for inducing apoptosis of tumor cells and/or for delaying, preventing, or treating acquired resistance to RAS inhibitors using bi-steric mTOR inhibitors.
Development of dual inhibitors targeting pyruvate dehydrogenase kinases and human lactate dehydrogenase A: High-throughput virtual screening, synthesis and biological validation
Xiang, Sichuan,Huang, Ding,He, Qiaolin,Li, Jie,Tam, Kin Yip,Zhang, Shao-Lin,He, Yun
, (2020/07/21)
Most cancer cells feature an altered glucose metabolism from oxidative phosphorylation to cytoplasmic glycolysis. Pyruvate dehydrogenase kinases (PDKs) and lactate dehydrogenase A (LDHA) play crucial roles in promotion of glycolysis, thus the inhibition of both enzymes is considered a promising strategy for developing of anticancer therapeutics. Herein, we describe the first discovery of series novel dual inhibitors targeting PDKs and LDHA. We identified 6 hits from a library database containing 485465 compounds through a high-throughput virtual screening assay. Hit-to-lead optimization enabled us to discover two compounds, namely 20e and 20k, which inhibited PDKs with IC50 values of 0.8, and 1.6 μM, respectively, and inhibited LDHA with IC50 values of 0.15 and 0.7 μM, respectively. Meanwhile, the two compounds reduced A549 cell proliferation with EC50 values of 13.2, and 15.7 μM. Furthermore, 20e and 20k decreased the lactate formation, and increased oxygen consumption, suggesting the two compounds modulated the glucose metabolic pathways in cancer cells.
C26-LINKED RAPAMYCIN ANALOGS AS MTOR INHIBITORS
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, (2019/11/21)
The present disclosure relates to mTOR inhibitors. Specifically, the embodiments are directed to compounds and compositions inhibiting mTOR, methods of treating diseases mediated by mTOR, and methods of synthesizing these compounds.
