Rapamycin passes the torch: a new generation of mTOR inhibitors

Role of mTOR Signaling in Tumor Cell Motility, Invasion and Metastasis

(2012) Shile Huang et al.   CURRENT PROTEIN & PEPTIDE SCIENCE

Abstract B148: INK128 is a potent and selective TORC1/2 inhibitor with broad oral antitumor activity

(2012) K. Jessen et al.   MOLECULAR CANCER THERAPEUTICS

Benefits of mTOR kinase targeting in oncology: pre-clinical evidence with AZD8055: Figure 1

(2011) Gayle Marshall et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

Reduced VEGF Production, Angiogenesis, and Vascular Regrowth Contribute to the Antitumor Properties of Dual mTORC1/mTORC2 Inhibitors

(2011) B. L. Falcon et al.   CANCER RESEARCH

Activation of mTORC2 by Association with the Ribosome

(2011) Vittoria Zinzalla et al.   CELL

Cardiac Raptor Ablation Impairs Adaptive Hypertrophy, Alters Metabolic Gene Expression, and Causes Heart Failure in Mice

(2011) Pankaj Shende et al.   CIRCULATION

Recent Advances in the Therapeutic Perspectives of Nutlin-3

(2011) Paola Secchiero et al.   CURRENT PHARMACEUTICAL DESIGN

Rictor/mTORC2 Is Essential for Maintaining a Balance Between β-Cell Proliferation and Cell Size

(2011) Yanyun Gu et al.   DIABETES

Targeting the mTOR kinase domain: the second generation of mTOR inhibitors

(2011) Yan-Jie Zhang et al.   DRUG DISCOVERY TODAY

The TORC1/TORC2 inhibitor, Palomid 529, reduces tumor growth and sensitizes to docetaxel and cisplatin in aggressive and hormone-refractory prostate cancer cells

(2011) G. L. Gravina et al.   ENDOCRINE-RELATED CANCER

Recent advances in the discovery of small-molecule ATP competitive mTOR inhibitors: a patent review

(2011) Arie Zask et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

Phospholipase D Regulates Myogenic Differentiation through the Activation of Both mTORC1 and mTORC2 Complexes

(2011) Rami Jaafar et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Role of mTOR in podocyte function and diabetic nephropathy in humans and mice

(2011) Markus Gödel et al.   JOURNAL OF CLINICAL INVESTIGATION

Discovery of 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one (Torin2) as a Potent, Selective, and Orally Available Mammalian Target of Rapamycin (mTOR) Inhibitor for Treatment of Cancer

(2011) Qingsong Liu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Everolimus for Advanced Pancreatic Neuroendocrine Tumors

(2011) James C. Yao et al.   NEW ENGLAND JOURNAL OF MEDICINE

Targeting the Akt/mTOR pathway in Brca1-deficient cancers

(2011) T Xiang et al.   ONCOGENE

Mammalian Target of Rapamycin: Hitting the Bull's-Eye for Neurological Disorders

(2011) Zhao Zhong Chong et al.   Oxidative Medicine and Cellular Longevity

Phosphoproteomic Analysis Identifies Grb10 as an mTORC1 Substrate That Negatively Regulates Insulin Signaling

(2011) Y. Yu et al.   SCIENCE

The mTOR-Regulated Phosphoproteome Reveals a Mechanism of mTORC1-Mediated Inhibition of Growth Factor Signaling

(2011) P. P. Hsu et al.   SCIENCE

Rapamycin Reverses Cellular Phenotypes and Enhances Mutant Protein Clearance in Hutchinson-Gilford Progeria Syndrome Cells

(2011) K. Cao et al.   Science Translational Medicine

Simultaneous inhibition of mTORC1 and mTORC2 by mTOR kinase inhibitor AZD8055 induces autophagy and cell death in cancer cells

(2010) Patrizia Sini et al.   Autophagy

Genetic Dissection of the Oncogenic mTOR Pathway Reveals Druggable Addiction to Translational Control via 4EBP-eIF4E

(2010) Andrew C. Hsieh et al.   CANCER CELL

Beyond Rapalog Therapy: Preclinical Pharmacology and Antitumor Activity of WYE-125132, an ATP-Competitive and Specific Inhibitor of mTORC1 and mTORC2

(2010) K. Yu et al.   CANCER RESEARCH

Ragulator-Rag Complex Targets mTORC1 to the Lysosomal Surface and Is Necessary for Its Activation by Amino Acids

(2010) Yasemin Sancak et al.   CELL

Metformin, Independent of AMPK, Inhibits mTORC1 in a Rag GTPase-Dependent Manner

(2010) Adem Kalender et al.   Cell Metabolism

Vertical Targeting of the Phosphatidylinositol-3 Kinase Pathway as a Strategy for Treating Melanoma

(2010) S. A. Aziz et al.   CLINICAL CANCER RESEARCH

NVP-BEZ235 as a New Therapeutic Option for Sarcomas

(2010) M. C. Manara et al.   CLINICAL CANCER RESEARCH

Targeting Eukaryotic Translation Initiation Factor 4E (eIF4E) in Cancer

(2010) A. C. Hsieh et al.   CLINICAL CANCER RESEARCH

mTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt polypeptide

(2010) Won Jun Oh et al.   EMBO JOURNAL

mTOR regulation of autophagy

(2010) Chang Hwa Jung et al.   FEBS LETTERS

WJD008, a Dual Phosphatidylinositol 3-Kinase (PI3K)/Mammalian Target of Rapamycin Inhibitor, Prevents PI3K Signaling and Inhibits the Proliferation of Transformed Cells with Oncogenic PI3K Mutant

(2010) T. Li et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Insights into the domain and repeat architecture of target of rapamycin

(2010) Bruce A. Knutson   JOURNAL OF STRUCTURAL BIOLOGY

The Rapamycin-sensitive Phosphoproteome Reveals That TOR Controls Protein Kinase A Toward Some But Not All Substrates

(2010) Alexandre Soulard et al.   MOLECULAR BIOLOGY OF THE CELL

Dual Inhibition of Akt/Mammalian Target of Rapamycin Pathway byNanoparticle Albumin-Bound–Rapamycin and Perifosine Induces Antitumor Activity in Multiple Myeloma

(2010) Diana Cirstea et al.   MOLECULAR CANCER THERAPEUTICS

Antitumor Efficacy Profile of PKI-402, a Dual Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Inhibitor

(2010) Robert Mallon et al.   MOLECULAR CANCER THERAPEUTICS

Structure of the Human mTOR Complex I and Its Implications for Rapamycin Inhibition

(2010) Calvin K. Yip et al.   MOLECULAR CELL

Activation of a Metabolic Gene Regulatory Network Downstream of mTOR Complex 1

(2010) Katrin Düvel et al.   MOLECULAR CELL

mTORC1 controls fasting-induced ketogenesis and its modulation by ageing

(2010) Shomit Sengupta et al.   NATURE

Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor

(2010) Matthew R Janes et al.   NATURE MEDICINE

mTOR: from growth signal integration to cancer, diabetes and ageing

(2010) Roberto Zoncu et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Genome-wide shRNA screen reveals increased mitochondrial dependence upon mTORC2 addiction

(2010) M Colombi et al.   ONCOGENE

Everolimus: A Proliferation Signal Inhibitor with Clinical Applications in Organ Transplantation, Oncology, and Cardiology

(2010) Steven Gabardi et al.   PHARMACOTHERAPY

Critical roles for mTORC2- and rapamycin-insensitive mTORC1-complexes in growth and survival of BCR-ABL-expressing leukemic cells

(2010) Nathalie Carayol et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

mTORC1-Mediated Cell Proliferation, But Not Cell Growth, Controlled by the 4E-BPs

(2010) R. J. O. Dowling et al.   SCIENCE

Activating Mutations in TOR Are in Similar Structures As Oncogenic Mutations in PI3KCα

(2009) Thomas W. Sturgill et al.   ACS Chemical Biology

Myeloma cell growth inhibition is augmented by synchronous inhibition of the insulin-like growth factor-1 receptor by NVP-AEW541 and inhibition of mammalian target of rapamycin by Rad001

(2009) Philipp Baumann et al.   ANTI-CANCER DRUGS

Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR)

(2009) Juan M. García-Martínez et al.   BIOCHEMICAL JOURNAL

The novel Akt inhibitor Palomid 529 (P529) enhances the effect of radiotherapy in prostate cancer

(2009) R Diaz et al.   BRITISH JOURNAL OF CANCER

Metformin use and prostate cancer in Caucasian men: results from a population-based case–control study

(2009) Jonathan L. Wright et al.   CANCER CAUSES & CONTROL

mTOR Complex 2 Is Required for the Development of Prostate Cancer Induced by Pten Loss in Mice

(2009) David A. Guertin et al.   CANCER CELL

AZD8055 Is a Potent, Selective, and Orally Bioavailable ATP-Competitive Mammalian Target of Rapamycin Kinase Inhibitor with In vitro and In vivo Antitumor Activity

(2009) C. M. Chresta et al.   CANCER RESEARCH

Biochemical, Cellular, and In vivo Activity of Novel ATP-Competitive and Selective Inhibitors of the Mammalian Target of Rapamycin

(2009) K. Yu et al.   CANCER RESEARCH

New Users of Metformin Are at Low Risk of Incident Cancer: A cohort study among people with type 2 diabetes

(2009) G. Libby et al.   DIABETES CARE

The influence of glucose-lowering therapies on cancer risk in type 2 diabetes

(2009) C. J. Currie et al.   DIABETOLOGIA

Antidiabetic Therapies Affect Risk of Pancreatic Cancer

(2009) Donghui Li et al.   GASTROENTEROLOGY

Characterization of the rapamycin-sensitive phosphoproteome reveals that Sch9 is a central coordinator of protein synthesis

(2009) A. Huber et al.   GENES & DEVELOPMENT

GCN2 Protein Kinase Is Required to Activate Amino Acid Deprivation Responses in Mice Treated with the Anti-cancer Agent l-Asparaginase

(2009) Piyawan Bunpo et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

An ATP-competitive Mammalian Target of Rapamycin Inhibitor Reveals Rapamycin-resistant Functions of mTORC1

(2009) Carson C. Thoreen et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Muscle inactivation of mTOR causes metabolic and dystrophin defects leading to severe myopathy

(2009) Valérie Risson et al.   JOURNAL OF CELL BIOLOGY

Phase III Study to Evaluate Temsirolimus Compared With Investigator's Choice Therapy for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma

(2009) Georg Hess et al.   JOURNAL OF CLINICAL ONCOLOGY

Metformin and Pathologic Complete Responses to Neoadjuvant Chemotherapy in Diabetic Patients With Breast Cancer

(2009) Sao Jiralerspong et al.   JOURNAL OF CLINICAL ONCOLOGY

Hybrid Inhibitors of Phosphatidylinositol 3-Kinase (PI3K) and the Mammalian Target of Rapamycin (mTOR): Design, Synthesis, and Superior Antitumor Activity of Novel Wortmannin−Rapamycin Conjugates

(2009) Semiramis Ayral-Kaloustian et al.   JOURNAL OF MEDICINAL CHEMISTRY

Targeting Melanoma with Dual Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitors

(2009) R. Marone et al.   MOLECULAR CANCER RESEARCH

Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941

(2009) F. I. Raynaud et al.   MOLECULAR CANCER THERAPEUTICS

Mysterious Metformin

(2009) C. R. Chong et al.   ONCOLOGIST

mTOR complex 2 in adipose tissue negatively controls whole-body growth

(2009) N. Cybulski et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Differential Requirement of mTOR in Postmitotic Tissues and Tumorigenesis

(2009) C. Nardella et al.   Science Signaling

Active-Site Inhibitors of mTOR Target Rapamycin-Resistant Outputs of mTORC1 and mTORC2

(2009) Morris E Feldman et al.   PLOS BIOLOGY

mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1)

(2008) Juan M. García-Martínez et al.   BIOCHEMICAL JOURNAL

A Vascular Targeted Pan Phosphoinositide 3-Kinase Inhibitor Prodrug, SF1126, with Antitumor and Antiangiogenic Activity

(2008) J. R. Garlich et al.   CANCER RESEARCH

Palomid 529, a Novel Small-Molecule Drug, Is a TORC1/TORC2 Inhibitor That Reduces Tumor Growth, Tumor Angiogenesis, and Vascular Permeability

(2008) Q. Xue et al.   CANCER RESEARCH

ABT-263: A Potent and Orally Bioavailable Bcl-2 Family Inhibitor

(2008) C. Tse et al.   CANCER RESEARCH

Adipose-Specific Knockout of raptor Results in Lean Mice with Enhanced Mitochondrial Respiration

(2008) Pazit Polak et al.   Cell Metabolism

Mediobasal Hypothalamic p70 S6 Kinase 1 Modulates the Control of Energy Homeostasis

(2008) Clémence Blouet et al.   Cell Metabolism

Skeletal Muscle-Specific Ablation of raptor, but Not of rictor, Causes Metabolic Changes and Results in Muscle Dystrophy

(2008) C. Florian Bentzinger et al.   Cell Metabolism

Temsirolimus, an Inhibitor of Mammalian Target of Rapamycin

(2008) B. I. Rini   CLINICAL CANCER RESEARCH

Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling

(2008) Tsuneo Ikenoue et al.   EMBO JOURNAL

The novel orally bioavailable inhibitor of phosphoinositol-3-kinase and mammalian target of rapamycin, NVP-BEZ235, inhibits growth and proliferation in multiple myeloma

(2008) Philipp Baumann et al.   EXPERIMENTAL CELL RESEARCH

Deforolimus (AP23573) a novel mTOR inhibitor in clinical development

(2008) Monica Mita et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Dose- and Schedule-Dependent Inhibition of the Mammalian Target of Rapamycin Pathway With Everolimus: A Phase I Tumor Pharmacodynamic Study in Patients With Advanced Solid Tumors

(2008) Josep Tabernero et al.   JOURNAL OF CLINICAL ONCOLOGY

First-in-class, first-in-human phase I results of targeted agents: Highlights of the 2008 American Society of Clinical Oncology meeting

(2008) Andrea Molckovsky et al.   Journal of Hematology & Oncology

Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial

(2008) Robert J Motzer et al.   LANCET

AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint

(2008) Dana M. Gwinn et al.   MOLECULAR CELL

Regulation of TORC1 by Rag GTPases in nutrient response

(2008) Eunjung Kim et al.   NATURE CELL BIOLOGY

Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases

(2008) Beth Apsel et al.   Nature Chemical Biology

Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers

(2008) Jeffrey A Engelman et al.   NATURE MEDICINE

Sirolimus for Angiomyolipoma in Tuberous Sclerosis Complex or Lymphangioleiomyomatosis

(2008) John J. Bissler et al.   NEW ENGLAND JOURNAL OF MEDICINE

Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation

(2008) A. Y. Choo et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1

(2008) Y. Sancak et al.   SCIENCE