Biochemical, cellular, and in vivo activity of novel ATP-competitive and selective inhibitors of the mammalian target of rapamycin.
- Ker Yu, L. Toral-Barza, A. Zask
- Biology, ChemistryCancer Research
- 1 August 2009
Three pyrazolopyrimidine ATP-competitive mTOR inhibitors are reported, with significant selectivity over phosphatidylinositol 3-kinase (PI3K) isofoms (>100-fold), to highlight mechanistic differentiation between rapalogs and mTOR kinase inhibitors in targeting cancer cell growth and survival and provide support for clinical development of mTORKinase inhibitors as new cancer therapy.
Requirement of the mTOR Kinase for the Regulation of Maf1 Phosphorylation and Control of RNA Polymerase III-dependent Transcription in Cancer Cells
- Boris Shor, Jiang Wu, Ker Yu
- Biology, ChemistryJournal of Biological Chemistry
- 16 March 2010
The mammalian target of rapamycin (mTOR) regulates growth via promoting translation and transcription. Here, employing an mTOR active-site inhibitor WYE-125132 (WYE-132), we have performed…
Cpc2/RACK1 Is a Ribosome-associated Protein That Promotes Efficient Translation in Schizosaccharomyces pombe*
- Boris Shor, J. Calaycay, J. Rushbrook, M. Mcleod
- BiologyJournal of Biological Chemistry
- 5 December 2003
Evidence is provided that Cpc2 is associated with the ribosome, a highly conserved WD domain protein found in all eucaryotes that functions on mammalian signal transduction pathways and which is probably regulated at the level of translation.
Targeting mTOR globally in cancer: Thinking beyond rapamycin
- Boris Shor, J. Gibbons, R. Abraham, Ker Yu
- Biology, ChemistryCell Cycle
- 1 December 2009
Recent studies that highlight the emergence of rapamycin-resistant mTOR function in protein synthesis, cell growth, survival and metabolism are discussed, and it is shown that these rap amycin- resistant mTOR functions are profoundly inhibited by TKIs.
Beyond rapalog therapy: preclinical pharmacology and antitumor activity of WYE-125132, an ATP-competitive and specific inhibitor of mTORC1 and mTORC2.
- Ker Yu, C. Shi, J. Gibbons
- Biology, MedicineCancer Research
- 15 January 2010
The results further validate mTOR as a critical driver for tumor growth, establish WYE-132 as a potent and profound anticancer agent, and provide a strong rationale for clinical development of specific mTOR kinase inhibitors as new cancer therapy.
A new pharmacologic action of CCI-779 involves FKBP12-independent inhibition of mTOR kinase activity and profound repression of global protein synthesis.
- Boris Shor, Wei-guo Zhang, Ker Yu
- Biology, ChemistryCancer Research
- 15 April 2008
It is reported that, at clinically relevant low micromolar concentrations, CCI-779 completely suppressed proliferation of a broad panel of tumor cells and suggests that high-dose CCi-779 inhibits mTOR signaling through an FKBP12-independent mechanism that leads to profound translational repression.
Preclinical and clinical development of inotuzumab-ozogamicin in hematological malignancies.
- Boris Shor, H. Gerber, P. Sapra
- Biology, ChemistryMolecular Immunology
- 1 October 2015
Monoclonal antibody-based therapies in cancer: advances and challenges.
- P. Sapra, Boris Shor
- BiologyPharmacology and Therapeutics
- 1 June 2013
Cpc2, a Fission Yeast Homologue of Mammalian RACK1 Protein, Interacts with Ran1 (Pat1) Kinase To Regulate Cell Cycle Progression and Meiotic Development
- M. Mcleod, Boris Shor, A. Caporaso, Wei Wang, H. Chen, Lin Hu
- BiologyMolecular and Cellular Biology
- 1 June 2000
Fission yeast cpc2 may function as an anchoring protein for Ran1 (Pat1) kinase, in parallel with the proposed role of RACK1 in mammalian cells, and all defects associated with loss of cPC2 are reversed in cells expressing mammalian Rack1, demonstrating that the fission yeast and mammalian gene products are indeed functional homologues.
Preclinical to Clinical Translation of Antibody-Drug Conjugates Using PK/PD Modeling: a Retrospective Analysis of Inotuzumab Ozogamicin
- A. Betts, N. Haddish-Berhane, T. R. Johnson
- Biology, ChemistryAAPS Journal
- 19 May 2016
A multiscale, mechanism-based model has been developed for inotuzumab ozogamicin, which can integrate preclinical biomeasures and PK/PD data to predict clinical response and indicated that tumor growth is a highly sensitive parameter and predictive of successful outcome.
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