Novel antiplatelet strategies targeting GPVI, CLEC-2 and tyrosine kinases

Discovery of LOU064 (Remibrutinib), a Potent and Highly Selective Covalent Inhibitor of Bruton’s Tyrosine Kinase

(2020) Daniela Angst et al.   JOURNAL OF MEDICINAL CHEMISTRY

A Comprehensive Tyrosine Phosphoproteomic Analysis Reveals Novel Components of the Platelet CLEC-2 Signaling Cascade

(2020) Irene Izquierdo et al.   THROMBOSIS AND HAEMOSTASIS

Discovery of Lanraplenib (GS-9876): A Once-Daily Spleen Tyrosine Kinase Inhibitor for Autoimmune Diseases

(2020) Peter Blomgren et al.   ACS Medicinal Chemistry Letters

Treatment of Patients with Relapsed or Refractory Mantle Cell Lymphoma With Zanubrutinib, a Selective Inhibitor of Bruton's Tyrosine Kinase

(2020) Yuqin Song et al.   CLINICAL CANCER RESEARCH

Heme induces human and mouse platelet activation through C-type-lectin-like receptor-2

(2020) Joshua H. Bourne et al.   HAEMATOLOGICA

ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia

(2020) Paolo Ghia et al.   JOURNAL OF CLINICAL ONCOLOGY

Treatment of relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with the BTK inhibitor zanubrutinib: phase 2, single-arm, multicenter study

(2020) Wei Xu et al.   Journal of Hematology & Oncology

The platelet receptor CLEC-2 blocks neutrophil mediated hepatic recovery in acetaminophen induced acute liver failure

(2020) Abhishek Chauhan et al.   Nature Communications

Fenebrutinib versus Placebo or Adalimumab in Rheumatoid Arthritis: A Randomized, Double-Blind, Phase II Trial (ANDES Study)

(2020) Stanley Cohen et al.   Arthritis & Rheumatology

Pharmacological Blockade of GPVI Promotes Thrombus Disaggregation in the Absence of Thrombin

(2020) Muhammad Usman Ahmed et al.   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

Phosphoproteomic quantitation and causal analysis reveal pathways in GPVI/ITAM-mediated platelet activation programs

(2020) Özgün Babur et al.   BLOOD

Zanubrutinib for the treatment of patients with Waldenström macroglobulinemia: three years of follow-up

(2020) Judith Trotman et al.   BLOOD

A rationale for blocking thromboinflammation in COVID-19 with Btk inhibitors

(2020) Phillip LR. Nicolson et al.   PLATELETS

The collagen receptor glycoprotein VI promotes platelet-mediated aggregation of β-amyloid

(2020) Lili Donner et al.   Science Signaling

Analysis of platelets from a diet-induced obesity rat model: elucidating platelet dysfunction in obesity

(2020) María N. Barrachina et al.   Scientific Reports

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

(2020) Mark Roschewski et al.   Science Immunology

Flow studies on human GPVI-deficient blood under coagulating and noncoagulating conditions

(2020) Magdolna Nagy et al.   Blood Advances

Functional significance of the platelet immune receptors GPVI and CLEC-2

(2019) Julie Rayes et al.   JOURNAL OF CLINICAL INVESTIGATION

Platelet Glycoprotein VI Haplotypes and the Presentation of Paediatric Sepsis

(2019) Ahmed Asfari et al.   THROMBOSIS AND HAEMOSTASIS

Optimizing Platelet GPVI Inhibition versus Haemostatic Impairment by the Btk Inhibitors Ibrutinib, Acalabrutinib, ONO/GS-4059, BGB-3111 and Evobrutinib

(2019) Viola Denzinger et al.   THROMBOSIS AND HAEMOSTASIS

Discovery of Branebrutinib (BMS-986195): A Strategy for Identifying a Highly Potent and Selective Covalent Inhibitor Providing Rapid in Vivo Inactivation of Bruton’s Tyrosine Kinase (BTK)

(2019) Scott H. Watterson et al.   JOURNAL OF MEDICINAL CHEMISTRY

Long‐term fostamatinib treatment of adults with immune thrombocytopenia during the phase 3 clinical trial program

(2019) James B. Bussel et al.   AMERICAN JOURNAL OF HEMATOLOGY

Safety and Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT017, an Antiplatelet GPVI (Glycoprotein VI) Fab

(2019) Christine Voors-Pette et al.   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

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

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

Btk Inhibitors as First Oral Atherothrombosis-Selective Antiplatelet Drugs?

(2019) Kristina Busygina et al.   THROMBOSIS AND HAEMOSTASIS

Phase 1 study of selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL

(2019) Constantine Si Lun Tam et al.   BLOOD

Revacept, a Novel Inhibitor of Platelet Adhesion, in Patients Undergoing Elective PCI—Design and Rationale of the Randomized ISAR-PLASTER Trial

(2019) Stefanie Schüpke et al.   THROMBOSIS AND HAEMOSTASIS

Effect of Bruton's tyrosine kinase inhibitors on platelet aggregation in patients with acute myocardial infarction

(2019) Maria Bhatti et al.   THROMBOSIS RESEARCH

Understanding Fc Receptor Involvement in Inflammatory Diseases: From Mechanisms to New Therapeutic Tools

(2019) Sanae Ben Mkaddem et al.   Frontiers in Immunology

From Patients to Platelets and Back Again: Pharmacological Approaches to Glycoprotein VI, a Thrilling Antithrombotic Target with Minor Bleeding Risks

(2019) Augusto Martins Lima et al.   THROMBOSIS AND HAEMOSTASIS

Interspecies differences in protein expression do not impact the spatiotemporal regulation of glycoprotein VI mediated activation

(2019) Joanne L. Dunster et al.   JOURNAL OF THROMBOSIS AND HAEMOSTASIS

Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo-controlled trials

(2018) James Bussel et al.   AMERICAN JOURNAL OF HEMATOLOGY

Platelets play an essential role in murine lung development through Clec-2/podoplanin interaction

(2018) Nagaharu Tsukiji et al.   BLOOD

Oral Bruton tyrosine kinase inhibitors selectively block atherosclerotic plaque–triggered thrombus formation in humans

(2018) Kristina Busygina et al.   BLOOD

The effect of Bruton's tyrosine kinase (BTK) inhibitors on collagen-induced platelet aggregation, BTK, and tyrosine kinase expressed in hepatocellular carcinoma (TEC)

(2018) Jun Chen et al.   EUROPEAN JOURNAL OF HAEMATOLOGY

Immobilized fibrinogen activates human platelets through glycoprotein VI

(2018) Pierre H Mangin et al.   HAEMATOLOGICA

The contribution of platelet glycoprotein receptors to inflammatory bleeding prevention is stimulus and organ dependent

(2018) Julie Rayes et al.   HAEMATOLOGICA

Inhibition of Btk by Btk-specific concentrations of ibrutinib and acalabrutinib delays but does not block platelet aggregation to GPVI

(2018) Phillip L.R. Nicolson et al.   HAEMATOLOGICA

Dimeric Glycoprotein VI Binds to Collagen but Not to Fibrin

(2018) Mariam Ebrahim et al.   THROMBOSIS AND HAEMOSTASIS

Immobilized fibrinogen activates human platelets through glycoprotein VI

(2018) Pierre H Mangin et al.   HAEMATOLOGICA

The contribution of platelet glycoprotein receptors to inflammatory bleeding prevention is stimulus and organ dependent

(2018) Julie Rayes et al.   HAEMATOLOGICA

Inhibition of Btk by Btk-specific concentrations of ibrutinib and acalabrutinib delays but does not block platelet aggregation to GPVI

(2018) Phillip L.R. Nicolson et al.   HAEMATOLOGICA

Risk of Major Bleeding with Ibrutinib

(2018) Joseph Mock et al.   Clinical Lymphoma Myeloma & Leukemia

Effects of GS-9876, a novel spleen tyrosine kinase inhibitor, on platelet function and systemic hemostasis

(2018) Astrid S. Clarke et al.   THROMBOSIS RESEARCH

Salmonella-induced thrombi in mice develop asynchronously in the spleen and liver and are not effective bacterial traps

(2018) Nonantzin Beristain-Covarrubias et al.   BLOOD

GPVI surface expression and signalling pathway activation are increased in platelets from obese patients: Elucidating potential anti-atherothrombotic targets in obesity

(2018) María N. Barrachina et al.   ATHEROSCLEROSIS

Anti-GPVI Fab SAR264565 effectively blocks GPVI function in ex vivo human platelets under arterial shear in a perfusion chamber

(2017) Peter Florian et al.   EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY

Syk Activity Is Dispensable for Platelet GP1b-IX-V Signaling

(2017) Rachit Badolia et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Acalabrutinib (ACP-196): A Covalent Bruton Tyrosine Kinase Inhibitor with a Differentiated Selectivity and In Vivo Potency Profile

(2017) Tjeerd Barf et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Ibrutinib-associated bleeding: pathogenesis, management and risk reduction strategies

(2017) J. J. Shatzel et al.   JOURNAL OF THROMBOSIS AND HAEMOSTASIS

Design, development and characterization of ACT017, a humanized Fab that blocks platelet's glycoprotein VI function without causing bleeding risks

(2017) Kristell Lebozec et al.   mAbs

Soluble glycoprotein VI, a specific marker of platelet activation is increased in the plasma of subjects with seropositive rheumatoid arthritis

(2017) John R. Stack et al.   PLoS One

Recombinant GPVI-Fc added to single or dual antiplatelet therapy in vitro prevents plaque-induced platelet thrombus formation

(2017) Ann-Katrin Mojica Muñoz et al.   THROMBOSIS AND HAEMOSTASIS

Discovery of Potent and Selective Tricyclic Inhibitors of Bruton’s Tyrosine Kinase with Improved Druglike Properties

(2017) Xiaojing Wang et al.   ACS Medicinal Chemistry Letters

The podoplanin-CLEC-2 axis inhibits inflammation in sepsis

(2017) Julie Rayes et al.   Nature Communications

ADPase CD39 Fused to Glycoprotein VI‐Fc Boosts Local Antithrombotic Effects at Vascular Lesions

(2017) Heidrun Degen et al.   Journal of the American Heart Association

Syk Inhibition in Ischemic Stroke

(2016) Steven E. McKenzie   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

The Novel Oral Syk Inhibitor, Bl1002494, Protects Mice From Arterial Thrombosis and Thromboinflammatory Brain InfarctionHighlights

(2016) Judith M.M. van Eeuwijk et al.   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

Platelet Hyperreactivity in Diabetes: Focus on GPVI Signaling—Are Useful Drugs Already Available?

(2016) Jane F. Arthur et al.   DIABETES

Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor

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

Mechanical circulatory support is associated with loss of platelet receptors glycoprotein Ibα and glycoprotein VI

(2016) P. Lukito et al.   JOURNAL OF THROMBOSIS AND HAEMOSTASIS

Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia

(2016) John C. Byrd et al.   NEW ENGLAND JOURNAL OF MEDICINE

Platelet Activation: The Mechanisms and Potential Biomarkers

(2016) Seong-Hoon Yun et al.   Biomed Research International

Ibrutinib Inhibits Platelet Integrin αIIbβ3Outside-In Signaling and Thrombus Stability But Not Adhesion to CollagenSignificance

(2015) Alexander P. Bye et al.   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

Impact of the PI3-kinase/Akt pathway on ITAM and hemITAM receptors: Haemostasis, platelet activation and antithrombotic therapy

(2015) Alyssa J. Moroi et al.   BIOCHEMICAL PHARMACOLOGY

An open-label phase 2 trial of entospletinib (GS-9973), a selective spleen tyrosine kinase inhibitor, in chronic lymphocytic leukemia

(2015) J. Sharman et al.   BLOOD

Platelet glycoprotein VI binds to polymerized fibrin and promotes thrombin generation

(2015) E. Mammadova-Bach et al.   BLOOD

Fibrin activates GPVI in human and mouse platelets

(2015) O. M. Alshehri et al.   BLOOD

A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies

(2015) H. S. Walter et al.   BLOOD

Three-year follow-up of treatment-naive and previously treated patients with CLL and SLL receiving single-agent ibrutinib

(2015) J. C. Byrd et al.   BLOOD

Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results

(2015) M. L. Wang et al.   BLOOD

The expression of mouse CLEC-2 on leucocyte subsets varies according to their anatomical location and inflammatory state

(2015) Kate L. Lowe et al.   EUROPEAN JOURNAL OF IMMUNOLOGY

Antiplatelet therapy in acute coronary syndromes

(2015) Erik L Grove et al.   EXPERT OPINION ON PHARMACOTHERAPY

The platelet Fc receptor, FcγRIIa

(2015) Jianlin Qiao et al.   IMMUNOLOGICAL REVIEWS

Inflammation drives thrombosis after Salmonella infection via CLEC-2 on platelets

(2015) Jessica R. Hitchcock et al.   JOURNAL OF CLINICAL INVESTIGATION

Prolonged and tunable residence time using reversible covalent kinase inhibitors

(2015) J Michael Bradshaw et al.   Nature Chemical Biology

The role of platelets in inflammation

(2015) Robert Storey et al.   THROMBOSIS AND HAEMOSTASIS

Targeting Glycoprotein VI and the Immunoreceptor Tyrosine-Based Activation Motif Signaling Pathway

(2014) David Stegner et al.   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

CLEC-2 expression is maintained on activated platelets and on platelet microparticles

(2014) E. Gitz et al.   BLOOD

Ibrutinib treatment affects collagen and von Willebrand factor-dependent platelet functions

(2014) M. Levade et al.   BLOOD

Ibrutinib increases the risk of atrial fibrillation, potentially through inhibition of cardiac PI3K-Akt signaling

(2014) J. R. McMullen et al.   BLOOD

Src family kinases: at the forefront of platelet activation

(2014) Y. A. Senis et al.   BLOOD

New advances in treating thrombotic diseases: GPVI as a platelet drug target

(2014) Peng Jiang et al.   DRUG DISCOVERY TODAY

Copy Number Analysis of the Murine Platelet Proteome Spanning the Complete Abundance Range

(2014) Marlis Zeiler et al.   MOLECULAR & CELLULAR PROTEOMICS

Ibrutinib versus Ofatumumab in Previously Treated Chronic Lymphoid Leukemia

(2014) John C. Byrd et al.   NEW ENGLAND JOURNAL OF MEDICINE

Combined In Vivo Depletion of Glycoprotein VI and C-Type Lectin-Like Receptor 2 Severely Compromises Hemostasis and Abrogates Arterial Thrombosis in Mice

(2013) Markus Bender et al.   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

Platelet receptors activated via mulitmerization: glycoprotein VI, GPIb-IX-V, and CLEC-2

(2013) Y. Ozaki et al.   JOURNAL OF THROMBOSIS AND HAEMOSTASIS

Targeting BTK with Ibrutinib in Relapsed or Refractory Mantle-Cell Lymphoma

(2013) Michael L. Wang et al.   NEW ENGLAND JOURNAL OF MEDICINE

Targeting BTK with Ibrutinib in Relapsed Chronic Lymphocytic Leukemia

(2013) John C. Byrd et al.   NEW ENGLAND JOURNAL OF MEDICINE

The GPVI-Fc Fusion Protein Revacept Improves Cerebral Infarct Volume and Functional Outcome in Stroke

(2013) Silvia Goebel et al.   PLoS One

The GPVI – Fc Fusion Protein Revacept Reduces Thrombus Formation and Improves Vascular Dysfunction in Atherosclerosis without Any Impact on Bleeding Times

(2013) Martin Ungerer et al.   PLoS One

The dimeric platelet collagen receptor GPVI-Fc reduces platelet adhesion to activated endothelium and preserves myocardial function after transient ischemia in mice

(2012) Tanja Schönberger et al.   AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY

The first comprehensive and quantitative analysis of human platelet protein composition allows the comparative analysis of structural and functional pathways

(2012) J. M. Burkhart et al.   BLOOD

The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia

(2012) M. F. M. de Rooij et al.   BLOOD

The future of glycoprotein VI as an antithrombotic target

(2012) M. ZAHID et al.   JOURNAL OF THROMBOSIS AND HAEMOSTASIS

Critical role for Syk in responses to vascular injury

(2011) P. Andre et al.   BLOOD

Novel Antiplatelet Drug Revacept (Dimeric Glycoprotein VI-Fc) Specifically and Efficiently Inhibited Collagen-Induced Platelet Aggregation Without Affecting General Hemostasis in Humans

(2011) Martin Ungerer et al.   CIRCULATION

PRT-060318, a novel Syk inhibitor, prevents heparin-induced thrombocytopenia and thrombosis in a transgenic mouse model

(2010) M. P. Reilly et al.   BLOOD

CLEC-2 activates Syk through dimerization

(2010) C. E. Hughes et al.   BLOOD

Synergism between platelet collagen receptors defined using receptor-specific collagen-mimetic peptide substrata in flowing blood

(2010) N. Pugh et al.   BLOOD

Essentialin VivoRoles of the C-type Lectin Receptor CLEC-2

(2010) Katsue Suzuki-Inoue et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Syk-dependent Phosphorylation of CLEC-2

(2010) Sonia Séverin et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Impact of glycoprotein VI and platelet adhesion on atherosclerosis—A possible role of fibronectin

(2010) Andreas Bültmann et al.   JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY

GPVI and CLEC-2 in hemostasis and vascular integrity

(2010) S. P. WATSON et al.   JOURNAL OF THROMBOSIS AND HAEMOSTASIS

CLEC-2 is not required for platelet aggregation at arteriolar shear

(2010) C. E. HUGHES et al.   JOURNAL OF THROMBOSIS AND HAEMOSTASIS

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

CLEC-2 is an essential platelet-activating receptor in hemostasis and thrombosis

(2009) F. May et al.   BLOOD

Design and humanization of a murine scFv that blocks human platelet glycoprotein VIin vitro

(2009) Julien Muzard et al.   FEBS Journal

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

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

The novel Syk inhibitor R406 reveals mechanistic differences in the initiation of GPVI and CLEC-2 signaling in platelets

(2009) J. C. SPALTON et al.   JOURNAL OF THROMBOSIS AND HAEMOSTASIS

The immunoadhesin glycoprotein VI-Fc regulates arterial remodelling after mechanical injury in ApoE−/− mice

(2008) Tanja Schönberger et al.   CARDIOVASCULAR RESEARCH

Compromised ITAM-based platelet receptor function in a patient with immune thrombocytopenic purpura

(2008) E. E. GARDINER et al.   JOURNAL OF THROMBOSIS AND HAEMOSTASIS