Emerging small-molecule inhibitors of the Bruton’s Tyrosine Kinase (BTK): current development

Zanubrutinib: First Approval

(2020) Yahiya Y. Syed   DRUGS

Ibrutinib in Chronic Lymphocytic Leukemia: Clinical Applications, Drug Resistance, and Prospects

(2020) Hong Zhou et al.   OncoTargets and Therapy

Acalabrutinib and Its Therapeutic Potential in the Treatment of Chronic Lymphocytic Leukemia: A Short Review on Emerging Data

(2020) Krista Isaac et al.   Cancer Management and Research

The role of Bruton’s tyrosine kinase inhibitors in the management of mantle cell lymphoma

(2020) Kirollos S Hanna et al.   JOURNAL OF ONCOLOGY PHARMACY PRACTICE

Discovery of quinoline-based irreversible BTK inhibitors

(2020) Gerjan de Bruin et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery of potent and highly selective covalent inhibitors of Bruton’s tyrosine kinase bearing triazine scaffold

(2020) Yu Teng et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Evaluating the Therapeutic Potential of Zanubrutinib in the Treatment of Relapsed/Refractory Mantle Cell Lymphoma: Evidence to Date

(2020) Yazeed Sawalha et al.   OncoTargets and Therapy

Inhibition of Bruton tyrosine kinase in patients with severe COVID-19

(2020) Mark Roschewski et al.   Science Immunology

ZYBT1, a potent, irreversible Bruton’s Tyrosine Kinase (BTK) inhibitor that inhibits the C481S BTK with profound efficacy against arthritis and cancer

(2020) Krishnarup Ghoshdastidar et al.   Pharmacology Research & Perspectives

Potent, non-covalent reversible BTK inhibitors with 8-amino-imidazo[1,5-a]pyrazine core featuring 3-position bicyclic ring substitutes

(2020) Jian Liu et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Kinase inhibition in autoimmunity and inflammation

(2020) Ali A. Zarrin et al.   NATURE REVIEWS DRUG DISCOVERY

HZ-A-005, a potent, selective, and covalent Bruton’s tyrosine kinase inhibitor in preclinical development

(2020) Wenhai Huang et al.   BIOORGANIC CHEMISTRY

Synthesis and biological activity of imidazole group-substituted arylaminopyrimidines (IAAPs) as potent BTK inhibitors against B-cell lymphoma and AML

(2020) Si Li et al.   BIOORGANIC CHEMISTRY

Managing toxicities of Bruton tyrosine kinase inhibitors

(2020) Andrew Lipsky et al.   Hematology-American Society of Hematology Education Program

Bruton’s tyrosine kinase (BTK) inhibitors in treating cancer: a patent review (2010-2018)

(2019) Yifan Feng et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

Optimization of novel reversible Bruton’s tyrosine kinase inhibitors identified using Tethering-fragment-based screens

(2019) Brian T. Hopkins et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Discovery of pyrazolopyrimidine derivatives as potent BTK inhibitors with effective anticancer activity in MCL

(2019) Fansheng Ran et al.   BIOORGANIC CHEMISTRY

Review of Bruton tyrosine kinase inhibitors for the treatment of relapsed or refractory mantle cell lymphoma

(2019) C. Owen et al.   Current Oncology

Design, synthesis and evaluation of novel 7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives as potent, selective and reversible Bruton's tyrosine kinase (BTK) inhibitors for the treatment of rheumatoid arthritis

(2019) Chufeng Zhang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Efficacy and Pharmacodynamic Modeling of the BTK Inhibitor Evobrutinib in Autoimmune Disease Models

(2019) Philipp Haselmayer et al.   JOURNAL OF IMMUNOLOGY

Placebo-Controlled Trial of an Oral BTK Inhibitor in Multiple Sclerosis

(2019) Xavier Montalban et al.   NEW ENGLAND JOURNAL OF MEDICINE

Discovery and biological evaluation of N-(3-(7-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)-4-methyl-2-oxo-2H-pyrimido[4,5-d][1,3]oxazin-1(4H)-yl)phenyl)acrylamide as potent Bruton’s tyrosine kinase inhibitors

(2019) Meng-zhen Lai et al.   ACTA PHARMACOLOGICA SINICA

Design, synthesis and biological evaluation of novel dithiocarbamate-substituted diphenylaminopyrimidine derivatives as BTK inhibitors

(2019) Zheng Zhai et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Discovery of 4-Aminoquinoline-3-carboxamide Derivatives as Potent Reversible Bruton’s Tyrosine Kinase Inhibitors for the Treatment of Rheumatoid Arthritis

(2019) Xia Yao et al.   JOURNAL OF MEDICINAL CHEMISTRY

Ibrutinib related bleeding complications in elderly patients with B cell malignancies

(2019) Roberto Castelli et al.   JOURNAL OF THROMBOSIS AND THROMBOLYSIS

Discovery and Biological evaluation of pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione derivatives as potent Bruton’s tyrosine kinase inhibitors

(2019) Yanyan Diao et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Discovery and structure-activity relationship of novel diphenylthiazole derivatives as BTK inhibitor with potent activity against B cell lymphoma cell lines

(2019) Xiaofeng Guo et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Design of Potent and Selective Covalent Inhibitors of Bruton’s Tyrosine Kinase Targeting an Inactive Conformation

(2019) Robert Pulz et al.   ACS Medicinal Chemistry Letters

Design and synthesis of boron-containing diphenylpyrimidines as potent BTK and JAK3 dual inhibitors

(2019) Jing Ren et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Design and synthesis of novel 1-substituted 3-(6-phenoxypyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine analogs as selective BTK inhibitors for the treatment of mantle cell lymphoma

(2019) Fansheng Ran et al.   BIOORGANIC CHEMISTRY

New 2,6,9-trisubstituted purine derivatives as Bcr-Abl and Btk inhibitors and as promising agents against leukemia

(2019) Jeanluc Bertrand et al.   BIOORGANIC CHEMISTRY

Design, synthesis and biological evaluation of novel 3-substituted pyrazolopyrimidine derivatives as potent Bruton’s tyrosine kinase (BTK) inhibitors

(2018) Nan Zheng et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Novel amino acid-substituted diphenylpyrimidine derivatives as potent BTK inhibitors against B cell lymphoma cell lines

(2018) Changyuan Wang et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Discovery of potent, highly selective covalent irreversible BTK inhibitors from a fragment hit

(2018) Hui Qiu et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Design and synthesis of novel pyrimidine analogs as highly selective, non-covalent BTK inhibitors

(2018) Wataru Kawahata et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Design, synthesis and biological evaluation of 7 H -pyrrolo[2,3- d ]pyrimidin-4-amine derivatives as selective Btk inhibitors with improved pharmacokinetic properties for the treatment of rheumatoid arthritis

(2018) Linhong He et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Identification of highly potent BTK and JAK3 dual inhibitors with improved activity for the treatment of B-cell lymphoma

(2018) Yang Ge et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of 4,7-Diamino-5-(4-phenoxyphenyl)-6-methylene-pyrimido[5,4-b]pyrrolizines as Novel Bruton’s Tyrosine Kinase Inhibitors

(2018) Yu Xue et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery and biological evaluation of N5-substituted 6,7-dioxo-6,7-dihydropteridine derivatives as potent Bruton's tyrosine kinase inhibitors

(2018) Haiyang Chen et al.   MedChemComm

Anti-cancer effect of a novel 2,3-didithiocarbamate-substituted naphthoquinone as a tumor metabolic suppressor in vitro and in vivo

(2018) Xianling Ning et al.   MedChemComm

Design and synthesis of benzofuro[3,2-b]pyridin-2(1H)-one derivatives as anti-leukemia agents by inhibiting Btk and PI3Kδ

(2018) Linyi Liu et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Optimization of the efflux ratio and permeability of covalent irreversible BTK inhibitors

(2018) Hui Qiu et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery of a novel series of pyridine and pyrimidine carboxamides as potent and selective covalent inhibitors of Btk

(2018) Richard Caldwell et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Design and Synthesis of Novel Amino-triazine Analogues as Selective Bruton’s Tyrosine Kinase Inhibitors for Treatment of Rheumatoid Arthritis

(2018) Wataru Kawahata et al.   JOURNAL OF MEDICINAL CHEMISTRY

Aminopyrazole Carboxamide Bruton’s Tyrosine Kinase Inhibitors. Irreversible to Reversible Covalent Reactive Group Tuning

(2018) Mark E. Schnute et al.   ACS Medicinal Chemistry Letters

Optimization of novel benzofuro[3,2-b]pyridin-2(1H)-one derivatives as dual inhibitors of BTK and PI3Kδ

(2018) Linyi Liu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of novel naphthoquinone derivatives as inhibitors of the tumor cell specific M2 isoform of pyruvate kinase

(2017) Xianling Ning et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Design and synthesis of formononetin-dithiocarbamate hybrids that inhibit growth and migration of PC-3 cells via MAPK/Wnt signaling pathways

(2017) Dong-Jun Fu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Structural optimization of diphenylpyrimidine derivatives (DPPYs) as potent Bruton's tyrosine kinase (BTK) inhibitors with improved activity toward B leukemia cell lines

(2017) Dan Zhao et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Enhanced Bruton's Tyrosine Kinase Activity in Peripheral Blood B Lymphocytes From Patients With Autoimmune Disease

(2017) Odilia B. J. Corneth et al.   Arthritis & Rheumatology

Structure-Guided Design of C4-alkyl-1,4-dihydro-2H-pyrimido[4,5-d][1,3]oxazin-2-ones as Potent and Mutant-Selective Epidermal Growth Factor Receptor (EGFR) L858R/T790M Inhibitors

(2017) Yongjia Hao et al.   Scientific Reports

Synthesis and biological evaluation of azole-diphenylpyrimidine derivatives (AzDPPYs) as potent T790M mutant form of epidermal growth factor receptor inhibitors

(2016) Zhendong Song et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Second-generation inhibitors of Bruton tyrosine kinase

(2016) Jingjing Wu et al.   Journal of Hematology & Oncology

Challenges and Perspectives on the Development of Small-Molecule EGFR Inhibitors against T790M-Mediated Resistance in Non-Small-Cell Lung Cancer

(2016) Zhendong Song et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery and Structural Optimization of N5-Substituted 6,7-Dioxo-6,7-dihydropteridines as Potent and Selective Epidermal Growth Factor Receptor (EGFR) Inhibitors against L858R/T790M Resistance Mutation

(2016) Yongjia Hao et al.   JOURNAL OF MEDICINAL CHEMISTRY

From identification of the BTK kinase to effective management of leukemia

(2016) C I E Smith   ONCOGENE

Discovery of Novel Bruton’s Tyrosine Kinase (BTK) Inhibitors Bearing a N,9-Diphenyl-9H-purin-2-amine Scaffold

(2016) Yang Ge et al.   ACS Medicinal Chemistry Letters

Fragment-Based Discovery of a Small Molecule Inhibitor of Bruton’s Tyrosine Kinase

(2015) Christopher R. Smith et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of a Potent, Covalent BTK Inhibitor for B-Cell Lymphoma

(2014) Hong Wu et al.   ACS Chemical Biology

Src family kinases: at the forefront of platelet activation

(2014) Y. A. Senis et al.   BLOOD

Structure-Based Drug Design of RN486, a Potent and Selective Bruton’s Tyrosine Kinase (BTK) Inhibitor, for the Treatment of Rheumatoid Arthritis

(2014) Yan Lou et al.   JOURNAL OF MEDICINAL CHEMISTRY

Selective Antitumor Activity of Ibrutinib in EGFR-Mutant Non–Small Cell Lung Cancer Cells

(2014) Wen Gao et al.   JNCI-Journal of the National Cancer Institute

A review of a novel, Bruton’s tyrosine kinase inhibitor, ibrutinib

(2014) Chung-Shien Lee et al.   JOURNAL OF ONCOLOGY PHARMACY PRACTICE

The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo

(2011) S. Ponader et al.   BLOOD

Neutrophil development and function critically depend on Bruton tyrosine kinase in a mouse model of X-linked agammaglobulinemia

(2010) K. Fiedler et al.   BLOOD

Specific Btk inhibition suppresses B cell– and myeloid cell–mediated arthritis

(2010) Julie A Di Paolo et al.   Nature Chemical Biology

The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy

(2010) L. A. Honigberg et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Structures of human Bruton's tyrosine kinase in active and inactive conformations suggest a mechanism of activation for TEC family kinases

(2010) Douglas J. Marcotte et al.   PROTEIN SCIENCE

Bruton’s tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain

(2009) Abdalla J. Mohamed et al.   IMMUNOLOGICAL REVIEWS

Novel mutant-selective EGFR kinase inhibitors against EGFR T790M

(2009) Wenjun Zhou et al.   NATURE

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