Recent advances in targeting mTOR signaling pathway using small molecule inhibitors

Preclinical evaluation of WYE-687, a mTOR kinase inhibitor, as a potential anti-acute myeloid leukemia agent

(2016) Feng Cheng et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway

(2016) Lynne Chantranupong et al.   CELL

Erratum: mTORC2 is a tyrosine kinase

(2016) Xuemin Wang et al.   CELL RESEARCH

A Randomised Phase 2 Study of AZD2014 Versus Everolimus in Patients with VEGF-Refractory Metastatic Clear Cell Renal Cancer

(2016) Thomas Powles et al.   EUROPEAN UROLOGY

Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study

(2016) James C Yao et al.   LANCET

TORC2 Structure and Function

(2016) Christl Gaubitz et al.   TRENDS IN BIOCHEMICAL SCIENCES

Mechanisms of tumor cell resistance to the current targeted-therapy agents

(2016) Gholamreza Khamisipour et al.   TUMOR BIOLOGY

Oral mucosal injury caused by mammalian target of rapamycin inhibitors: emerging perspectives on pathobiology and impact on clinical practice

(2016) Douglas E. Peterson et al.   Cancer Medicine

Toward rapamycin analog (rapalog)-based precision cancer therapy

(2015) Ling-hua Meng et al.   ACTA PHARMACOLOGICA SINICA

Dual mTORC1/2 inhibition by INK-128 results in antitumor activity in preclinical models of osteosarcoma

(2015) Haibin Jiang et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

DNA-PKcs interference sensitizes colorectal cancer cells to a mTOR kinase inhibitor WAY-600

(2015) Ling Wu et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Elevated Rictor expression is associated with tumor progression and poor prognosis in patients with gastric cancer

(2015) Yuhai Bian et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Autophagy inhibition sensitizes KU-0063794-mediated anti-HepG2 hepatocellular carcinoma cell activity in vitro and in vivo

(2015) Tong Yongxi et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Complications of hyperglycaemia with PI3K–AKT–mTOR inhibitors in patients with advanced solid tumours on Phase I clinical trials

(2015) E Geuna et al.   BRITISH JOURNAL OF CANCER

The preclinical evaluation of the dual mTORC1/2 inhibitor INK-128 as a potential anti-colorectal cancer agent

(2015) Chen Li et al.   CANCER BIOLOGY & THERAPY

Suppression of the GTPase-activating protein RGS10 increases Rheb-GTP and mTOR signaling in ovarian cancer cells

(2015) Molly K. Altman et al.   CANCER LETTERS

Pre-clinical evaluation of AZD-2014, a novel mTORC1/2 dual inhibitor, against renal cell carcinoma

(2015) Bing Zheng et al.   CANCER LETTERS

The AMP-activated protein kinase (AMPK) and cancer: Many faces of a metabolic regulator

(2015) Brandon Faubert et al.   CANCER LETTERS

Kinome RNAi Screens Reveal Synergistic Targeting of MTOR and FGFR1 Pathways for Treatment of Lung Cancer and HNSCC

(2015) K. R. Singleton et al.   CANCER RESEARCH

First-in-Human Pharmacokinetic and Pharmacodynamic Study of the Dual m-TORC 1/2 Inhibitor AZD2014

(2015) B. Basu et al.   CLINICAL CANCER RESEARCH

Cellular and molecular effects of the mTOR inhibitor everolimus

(2015) U. Saran et al.   CLINICAL SCIENCE

Results of a phase 1 trial combining ridaforolimus and MK-0752 in patients with advanced solid tumours

(2015) S.A. Piha-Paul et al.   EUROPEAN JOURNAL OF CANCER

Rheb signaling and tumorigenesis: mTORC1 and new horizons

(2015) Marisol E. Armijo et al.   INTERNATIONAL JOURNAL OF CANCER

Ibrutinib-A double-edge sword in cancer and autoimmune disorders

(2015) Parviz Kokhaei et al.   JOURNAL OF DRUG TARGETING

Targeting non-receptor tyrosine kinases using small molecule inhibitors: an overview of recent advances

(2015) Mohammad Hojjat-Farsangi   JOURNAL OF DRUG TARGETING

mTOR Complex 2 Stabilizes Mcl-1 Protein by Suppressing Its Glycogen Synthase Kinase 3-Dependent and SCF-FBXW7-Mediated Degradation

(2015) Junghui Koo et al.   MOLECULAR AND CELLULAR BIOLOGY

AZD2014, an Inhibitor of mTORC1 and mTORC2, Is Highly Effective in ER+ Breast Cancer When Administered Using Intermittent or Continuous Schedules

(2015) S. M. Guichard et al.   MOLECULAR CANCER THERAPEUTICS

Combination of mTOR Inhibitors Augments Potency while Activating PI3K Signaling in Pituitary Tumors

(2015) Hadara Rubinfeld et al.   NEUROENDOCRINOLOGY

Abrogation of Autophagy by Chloroquine Alone or in Combination with mTOR Inhibitors Induces Apoptosis in Neuroendocrine Tumor Cells

(2015) Shani Avniel-Polak et al.   NEUROENDOCRINOLOGY

Impact of Prior Chemotherapy Use on the Efficacy of Everolimus in Patients With Advanced Pancreatic Neuroendocrine Tumors

(2015) Catherine Lombard-Bohas et al.   PANCREAS

Sestrin2 is a leucine sensor for the mTORC1 pathway

(2015) R. L. Wolfson et al.   SCIENCE

Regulation of mTORC1 by PI3K signaling

(2015) Christian C. Dibble et al.   TRENDS IN CELL BIOLOGY

The anti-ovarian cancer activity by WYE-132, a mTORC1/2 dual inhibitor

(2015) Dan Zhang et al.   TUMOR BIOLOGY

Novel and emerging targeted-based cancer therapy agents and methods

(2015) Mohammad Hojjat-Farsangi   TUMOR BIOLOGY

Dual targeting of mTORC1 and mTORC2 by INK-128 potently inhibits human prostate cancer cell growth in vitro and in vivo

(2015) Shang-jun Jiang et al.   TUMOR BIOLOGY

A high-throughput kinome screen reveals serum/glucocorticoid-regulated kinase 1 as a therapeutic target for NF2-deficient meningiomas

(2015) Roberta L. Beauchamp et al.   Oncotarget

Point mutations of the mTOR-RHEB pathway in renal cell carcinoma

(2015) Arindam P. Ghosh et al.   Oncotarget

Rheb Inhibits Protein Synthesis by Activating the PERK-eIF2α Signaling Cascade

(2015) Richa Tyagi et al.   Cell Reports

A Positive Feedback Loop between Akt and mTORC2 via SIN1 Phosphorylation

(2015) Guang Yang et al.   Cell Reports

The Changes of Lipid Metabolism in Advanced Renal Cell Carcinoma Patients Treated with Everolimus: A New Pharmacodynamic Marker?

(2015) Francesco Pantano et al.   PLoS One

mLST8 Promotes mTOR-Mediated Tumor Progression

(2015) Kyoko Kakumoto et al.   PLoS One

Synergistic induction of apoptosis by combination of BTK and dual mTORC1/2 inhibitors in diffuse large B cell lymphoma

(2015) Scott A. Ezell et al.   Oncotarget

An Evolving Role for DEPTOR in Tumor Development and Progression

(2015) Zhiwei Wang et al.   NEOPLASIA

Incidence and risk of rash to mTOR inhibitors in cancer patients – a meta-analysis of randomized controlled trials

(2014) Raji Shameem et al.   ACTA ONCOLOGICA

Leucine facilitates the insulin-stimulated glucose uptake and insulin signaling in skeletal muscle cells: involving mTORC1 and mTORC2

(2014) Hui Liu et al.   AMINO ACIDS

PTEN

(2014) Carolyn A. Worby et al.   Annual Review of Biochemistry

PI3K/AKT/mTOR signaling pathway as a therapeutic target for ovarian cancer

(2014) HaiXia Li et al.   ARCHIVES OF GYNECOLOGY AND OBSTETRICS

The novel mTORC1/2 dual inhibitor INK-128 suppresses survival and proliferation of primary and transformed human pancreatic cancer cells

(2014) Hai-zhou Lou et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

The PI3K/AKT/mTOR pathway is involved in direct apoptosis of CLL cells induced by ROR1 monoclonal antibodies

(2014) Amir Hossein Daneshmanesh et al.   BRITISH JOURNAL OF HAEMATOLOGY

Feedback regulation of mTORC1 by Grb10 in metabolism and beyond

(2014) Bilian Liu et al.   CELL CYCLE

Small-Molecule Inhibitors of the Receptor Tyrosine Kinases: Promising Tools for Targeted Cancer Therapies

(2014) Mohammad Hojjat-Farsangi   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Efficacy, safety, pharmacokinetics and pharmacodynamics of SAR245409 (voxtalisib, XL765), an orally administered phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor: a phase 1 expansion cohort in patients with relapsed or refractory lymphoma

(2014) Kyriakos P. Papadopoulos et al.   LEUKEMIA & LYMPHOMA

Hyperactivation of mTORC1 and mTORC2 by multiple oncogenic events causes addiction to eIF4E-dependent mRNA translation in T-cell leukemia

(2014) A Schwarzer et al.   ONCOGENE

A Year in Structural Signaling: mTOR--The PIKK of the Bunch?

(2014) S. J. Smerdon   Science Signaling

Furthering the design and the discovery of small molecule ATP-competitive mTOR inhibitors as an effective cancer treatment

(2013) Xiaoqing Lv et al.   Expert Opinion on Drug Discovery

Rapamycin Induces Mitogen-activated Protein (MAP) Kinase Phosphatase-1 (MKP-1) Expression through Activation of Protein Kinase B and Mitogen-activated Protein Kinase Kinase Pathways

(2013) Ruchi Rastogi et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Discovery of a Novel Class of Highly Potent, Selective, ATP-Competitive, and Orally Bioavailable Inhibitors of the Mammalian Target of Rapamycin (mTOR)

(2013) Craig S. Takeuchi et al.   JOURNAL OF MEDICINAL CHEMISTRY

Sin1 phosphorylation impairs mTORC2 complex integrity and inhibits downstream Akt signalling to suppress tumorigenesis

(2013) Pengda Liu et al.   NATURE CELL BIOLOGY

The mTORC1/mTORC2 inhibitor AZD2014 enhances the radiosensitivity of glioblastoma stem-like cells

(2013) Jenna Kahn et al.   NEURO-ONCOLOGY

Different Patterns of Akt and ERK Feedback Activation in Response to Rapamycin, Active-Site mTOR Inhibitors and Metformin in Pancreatic Cancer Cells

(2013) Heloisa P. Soares et al.   PLoS One

TSC1 Controls Distribution of Actin Fibers through Its Effect on Function of Rho Family of Small GTPases and Regulates Cell Migration and Polarity

(2013) Maki Ohsawa et al.   PLoS One

Functional Role of mTORC2 versus Integrin-Linked Kinase in Mediating Ser473-Akt Phosphorylation in PTEN-Negative Prostate and Breast Cancer Cell Lines

(2013) Su-Lin Lee et al.   PLoS One

Targeting mTOR to Overcome Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Resistance in Non-Small Cell Lung Cancer Cells

(2013) Shi-Jiang Fei et al.   PLoS One

A Tumor Suppressor Complex with GAP Activity for the Rag GTPases That Signal Amino Acid Sufficiency to mTORC1

(2013) L. Bar-Peled et al.   SCIENCE

Regulation of Immune Responses by mTOR

(2012) Jonathan D. Powell et al.   Annual Review of Immunology

Serum and glucocorticoid-regulated kinase 1 (SGK1) activation in breast cancer: requirement for mTORC1 activity associates with ER-alpha expression

(2012) Ben A. Hall et al.   BREAST CANCER RESEARCH AND TREATMENT

Safety, tolerability, pharmacokinetics and pharmacodynamics of AZD8055 in advanced solid tumours and lymphoma

(2012) A Naing et al.   BRITISH JOURNAL OF CANCER

mTOR Signaling in Growth Control and Disease

(2012) Mathieu Laplante et al.   CELL

Dual mTORC1/2 and HER2 Blockade Results in Antitumor Activity in Preclinical Models of Breast Cancer Resistant to Anti-HER2 Therapy

(2012) C. Garcia-Garcia et al.   CLINICAL CANCER RESEARCH

Connecting mTORC1 signaling to SREBP-1 activation

(2012) Inan Bakan et al.   CURRENT OPINION IN LIPIDOLOGY

Targeting mTOR Pathways in Human Malignancies

(2012) Angelica Fasolo et al.   CURRENT PHARMACEUTICAL DESIGN

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

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

The mTOR Signalling Pathway in Human Cancer

(2012) Helena Pópulo et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Inhibition of mTORC1 Kinase Activates Smads 1 and 5 but Not Smad8 in Human Prostate Cancer Cells, Mediating Cytostatic Response to Rapamycin

(2012) Reema S. Wahdan-Alaswad et al.   MOLECULAR CANCER RESEARCH

TBC1D7 Is a Third Subunit of the TSC1-TSC2 Complex Upstream of mTORC1

(2012) Christian C. Dibble et al.   MOLECULAR CELL

ULK1 inhibits the kinase activity of mTORC1 and cell proliferation

(2011) Chang Hwa Jung et al.   Autophagy

ULK1 inhibits mTORC1 signaling, promotes multisite Raptor phosphorylation and hinders substrate binding

(2011) Elaine A. Dunlop et al.   Autophagy

Activation of mTORC2 by Association with the Ribosome

(2011) Vittoria Zinzalla et al.   CELL

mTOR Complex 1 Regulates Lipin 1 Localization to Control the SREBP Pathway

(2011) Timothy R. Peterson et al.   CELL

ATP-Competitive Inhibitors of mTOR: An Update

(2011) S. Schenone et al.   CURRENT MEDICINAL CHEMISTRY

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

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

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

Ridaforolimus (AP23573; MK-8669), a Potent mTOR Inhibitor, Has Broad Antitumor Activity and Can Be Optimally Administered Using Intermittent Dosing Regimens

(2011) V. M. Rivera et al.   MOLECULAR CANCER THERAPEUTICS

Preclinical Characterization of OSI-027, a Potent and Selective Inhibitor of mTORC1 and mTORC2: Distinct from Rapamycin

(2011) S. V. Bhagwat et al.   MOLECULAR CANCER THERAPEUTICS

Pushing the Envelope in the mTOR Pathway: The Second Generation of Inhibitors

(2011) E. Vilar et al.   MOLECULAR CANCER THERAPEUTICS

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

(2011) Y. Yu et al.   SCIENCE

Hypoxia and mitochondrial oxidative metabolism

(2010) Giancarlo Solaini et al.   BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS

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

Amino Acids Activate Mammalian Target of Rapamycin Complex 2 (mTORC2) via PI3K/Akt Signaling

(2010) Irantzu Tato et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Tti1 and Tel2 Are Critical Factors in Mammalian Target of Rapamycin Complex Assembly

(2010) Takeshi Kaizuka et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Multicenter Phase II Study of Everolimus in Patients With Previously Treated Metastatic Gastric Cancer

(2010) Toshihiko Doi et al.   JOURNAL OF CLINICAL ONCOLOGY

Bis(morpholino-1,3,5-triazine) Derivatives: Potent Adenosine 5′-Triphosphate Competitive Phosphatidylinositol-3-kinase/Mammalian Target of Rapamycin Inhibitors: Discovery of Compound26(PKI-587), a Highly Efficacious Dual Inhibitor

(2010) Aranapakam M. Venkatesan et al.   JOURNAL OF MEDICINAL CHEMISTRY

Single amino-acid changes that confer constitutive activation of mTOR are discovered in human cancer

(2010) T Sato et al.   ONCOGENE

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

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

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

DEPTOR Is an mTOR Inhibitor Frequently Overexpressed in Multiple Myeloma Cells and Required for Their Survival

(2009) Timothy R. Peterson et al.   CELL

A Phase I Trial to Determine the Safety, Tolerability, and Maximum Tolerated Dose of Deforolimus in Patients with Advanced Malignancies

(2009) C. M. Hartford et al.   CLINICAL CANCER RESEARCH

PI3K and mTOR inhibitors—a new generation of targeted anticancer agents

(2009) Saskia Brachmann et al.   CURRENT OPINION IN CELL BIOLOGY

Growth suppressive cytokines and the AKT/mTOR pathway

(2009) Barbara Kroczynska et al.   CYTOKINE

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

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

Targeting the phosphoinositide 3-kinase pathway in cancer

(2009) Pixu Liu et al.   NATURE REVIEWS DRUG DISCOVERY

Molecular mechanisms of mTOR-mediated translational control

(2009) Xiaoju Max Ma et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

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

(2009) Morris E Feldman et al.   PLOS BIOLOGY

The TSC1–TSC2 complex: a molecular switchboard controlling cell growth

(2008) Jingxiang Huang et al.   BIOCHEMICAL JOURNAL

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

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

A New Pharmacologic Action of CCI-779 Involves FKBP12-Independent Inhibition of mTOR Kinase Activity and Profound Repression of Global Protein Synthesis

(2008) B. Shor et al.   CANCER RESEARCH

mTOR Pathway and mTOR Inhibitors as Agents for Cancer Therapy

(2008) Paolo Baldo et al.   CURRENT CANCER DRUG TARGETS

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

(2008) Tsuneo Ikenoue et al.   EMBO JOURNAL

Class IA phosphatidylinositol 3-kinase: from their biologic implication in human cancers to drug discovery

(2008) Sauveur-Michel Maira et al.   EXPERT OPINION ON THERAPEUTIC TARGETS

Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity

(2008) S.-M. Maira et al.   MOLECULAR CANCER THERAPEUTICS

AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint

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

PI3K/Akt mediates expression of TNF-α mRNA and activation of NF-κB in calyculin A-treated primary osteoblasts

(2008) L Qiu et al.   ORAL DISEASES

Role of the Akt pathway in mRNA translation of interferon-stimulated genes

(2008) S. Kaur 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