Investigation of morpholine isosters for the development of a potent, selective and metabolically stable mTOR kinase inhibitor

The Tetrahydrofuran Motif in Polyketide Marine Drugs

(2022) Laura Fernández-Peña et al.   Marine Drugs

Covalent Proximity Scanning of a Distal Cysteine to Target PI3Kα

(2022) Chiara Borsari et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Challenges and Emerging Opportunities for Targeting mTOR in Cancer

(2022) Kris C. Wood et al.   CANCER RESEARCH

Brain-restricted mTOR inhibition with binary pharmacology

(2022) Ziyang Zhang et al.   NATURE

Advances in drug development for hepatocellular carcinoma: clinical trials and potential therapeutic targets

(2021) Xiang-Yuan Luo et al.   JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

Chemical and Structural Strategies to Selectively Target mTOR Kinase

(2021) Chiara Borsari et al.   ChemMedChem

Long-term Follow-up of Patients with Relapsed or Refractory Non–Hodgkin Lymphoma Treated with Venetoclax in a Phase I, First-in-Human Study

(2021) Matthew S. Davids et al.   CLINICAL CANCER RESEARCH

BH3 Mimetics in Hematologic Malignancies

(2021) Pavel Klener et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

The Anti-Non-Small Cell Lung Cancer Cell Activity by a mTOR Kinase Inhibitor PQR620

(2021) Jian-hua Zha et al.   Frontiers in Oncology

Targeting Phosphoinositide 3-Kinase – Five Decades of Chemical Space Exploration

(2021) Chiara Borsari et al.   CHIMIA

Morpholine as ubiquitous pharmacophore in medicinal chemistry: Deep insight into the structure-activity relationship (SAR)

(2020) Archana Kumari et al.   BIOORGANIC CHEMISTRY

Is There a Role for Dual PI3K/mTOR Inhibitors for Patients Affected with Lymphoma?

(2020) Chiara Tarantelli et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Discovery of a Brain-Penetrant ATP-Competitive Inhibitor of the Mechanistic Target of Rapamycin (mTOR) for CNS Disorders

(2020) Simone Bonazzi et al.   JOURNAL OF MEDICINAL CHEMISTRY

mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges

(2020) Zhilin Zou et al.   Cell and Bioscience

Novel brain permeant mTORC1/2 inhibitors are as efficacious as rapamycin or everolimus in mouse models of acquired partial epilepsy and tuberous sclerosis complex

(2020) Wiebke Theilmann et al.   NEUROPHARMACOLOGY

Discovery of 3-Oxabicyclo[4.1.0]heptane, a Non-nitrogen Containing Morpholine Isostere, and Its Application in Novel Inhibitors of the PI3K-AKT-mTOR Pathway

(2019) Heather Hobbs et al.   JOURNAL OF MEDICINAL CHEMISTRY

(S)-4-(Difluoromethyl)-5-(4-(3-methylmorpholino)-6-morpholino-1,3,5-triazin-2-yl)pyridin-2-amine (PQR530), a Potent, Orally Bioavailable, and Brain-Penetrable Dual Inhibitor of Class I PI3K and mTOR Kinase

(2019) Denise Rageot et al.   JOURNAL OF MEDICINAL CHEMISTRY

The Novel TORC1/2 Kinase Inhibitor PQR620 Has Anti-Tumor Activity in Lymphomas as a Single Agent and in Combination with Venetoclax

(2019) Chiara Tarantelli et al.   Cancers

A Conformational Restriction Strategy for the Identification of a Highly Selective Pyrimido-pyrrolo-oxazine mTOR Inhibitor

(2019) Chiara Borsari et al.   JOURNAL OF MEDICINAL CHEMISTRY

Preclinical Development of PQR514, a Highly Potent PI3K Inhibitor Bearing a Difluoromethyl–Pyrimidine Moiety

(2019) Chiara Borsari et al.   ACS Medicinal Chemistry Letters

Scalable, Economical, and Practical Synthesis of 4-(Difluoromethyl)pyridin-2-amine, a Key Intermediate for Lipid Kinase Inhibitors

(2019) Denise Rageot et al.   ORGANIC PROCESS RESEARCH & DEVELOPMENT

Brain-penetrant PQR620 mTOR and PQR530 PI3K/mTOR inhibitor reduce huntingtin levels in cell models of HD

(2019) Elisabeth Singer et al.   NEUROPHARMACOLOGY

Mercury 4.0: from visualization to analysis, design and prediction

(2019) Clare F. Macrae et al.   JOURNAL OF APPLIED CRYSTALLOGRAPHY

Discovery of a Potent, Orally Bioavailable PI4KIIIβ Inhibitor (UCB9608) Able To Significantly Prolong Allogeneic Organ Engraftment in Vivo

(2018) James Reuberson et al.   JOURNAL OF MEDICINAL CHEMISTRY

Suppression of insulin feedback enhances the efficacy of PI3K inhibitors

(2018) Benjamin D. Hopkins et al.   NATURE

The novel, catalytic mTORC1/2 inhibitor PQR620 and the PI3K/mTORC1/2 inhibitor PQR530 effectively cross the blood-brain barrier and increase seizure threshold in a mouse model of chronic epilepsy

(2018) Claudia Brandt et al.   NEUROPHARMACOLOGY

Discovery and Preclinical Characterization of 5-[4,6-Bis({3-oxa-8-azabicyclo[3.2.1]octan-8-yl})-1,3,5-triazin-2-yl]-4-(difluoromethyl)pyridin-2-amine (PQR620), a Highly Potent and Selective mTORC1/2 Inhibitor for Cancer and Neurological Disorders

(2018) Denise Rageot et al.   JOURNAL OF MEDICINAL CHEMISTRY

5-(4,6-Dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine (PQR309), a Potent, Brain-Penetrant, Orally Bioavailable, Pan-Class I PI3K/mTOR Inhibitor as Clinical Candidate in Oncology

(2017) Florent Beaufils et al.   JOURNAL OF MEDICINAL CHEMISTRY

A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis

(2017) Ujjini H. Manjunatha et al.   NATURE

Deconvolution of Buparlisib’s mechanism of action defines specific PI3K and tubulin inhibitors for therapeutic intervention

(2017) Thomas Bohnacker et al.   Nature Communications

Pharmacological use of a novel scaffold, anomeric N,N-diarylamino tetrahydropyran: molecular similarity search, chemocentric target profiling, and experimental evidence

(2017) Arramshetti Venkanna et al.   Scientific Reports

Toward rapamycin analog (rapalog)-based precision cancer therapy

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

CC-223, a Potent and Selective Inhibitor of mTOR Kinase: In Vitro and In Vivo Characterization

(2015) D. S. Mortensen et al.   MOLECULAR CANCER THERAPEUTICS

Crystal structure refinement withSHELXL

(2015) George M. Sheldrick   Acta Crystallographica Section C-Structural Chemistry

Clinical activity of everolimus in relapsed/refractory marginal zone B-cell lymphomas: results of a phase II study of the International Extranodal Lymphoma Study Group

(2014) Annarita Conconi et al.   BRITISH JOURNAL OF HAEMATOLOGY

MLN0128, an ATP-Competitive mTOR Kinase Inhibitor with Potent In Vitro and In Vivo Antitumor Activity, as Potential Therapy for Bone and Soft-Tissue Sarcoma

(2014) E. K. Slotkin et al.   MOLECULAR CANCER THERAPEUTICS

Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: The discovery of AZD8055 and AZD2014

(2013) Kurt G. Pike et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

mTOR kinase structure, mechanism and regulation

(2013) Haijuan Yang et al.   NATURE

Targeting Plasmodium PI(4)K to eliminate malaria

(2013) Case W. McNamara et al.   NATURE

EDMA: a computer program for topological analysis of discrete electron densities

(2012) Lukáš Palatinus et al.   JOURNAL OF APPLIED CRYSTALLOGRAPHY

Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks

(2011) Brian Magnuson et al.   BIOCHEMICAL JOURNAL

Triazines incorporating (R)-3-methylmorpholine are potent inhibitors of the mammalian target of rapamycin (mTOR) with selectivity over PI3Kα

(2010) David J. Richard et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

PKI-179: An orally efficacious dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor

(2010) Aranapakam M. Venkatesan et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

FDA Approval Summary: Temsirolimus as Treatment for Advanced Renal Cell Carcinoma

(2010) V. E. Kwitkowski et al.   ONCOLOGIST

Discovery of 2-arylthieno[3,2-d]pyrimidines containing 8-oxa-3-azabi-cyclo[3.2.1]octane in the 4-position as potent inhibitors of mTOR with selectivity over PI3K

(2009) Jeroen C. Verheijen et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery of 3,6-dihydro-2H-pyran as a morpholine replacement in 6-aryl-1H-pyrazolo[3,4-d]pyrimidines and 2-arylthieno[3,2-d]pyrimidines: ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR)

(2009) Joshua Kaplan et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Hydrogen-bond directionality at the donor H atom—analysis of interaction energies and database statistics

(2009) Peter A. Wood et al.   CRYSTENGCOMM

OLEX2: a complete structure solution, refinement and analysis program

(2009) Oleg V. Dolomanov et al.   JOURNAL OF APPLIED CRYSTALLOGRAPHY

Morpholine Derivatives Greatly Enhance the Selectivity of Mammalian Target of Rapamycin (mTOR) Inhibitors

(2009) Arie Zask et al.   JOURNAL OF MEDICINAL CHEMISTRY

A quantitative analysis of kinase inhibitor selectivity

(2008) Mazen W Karaman et al.   NATURE BIOTECHNOLOGY

Lipid signalling in disease

(2008) Matthias P. Wymann et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY