The recent advance of Interleukin-1 receptor associated kinase 4 inhibitors for the treatment of inflammation and related diseases

Targeting active sites of inflammation using inherent properties of tissue-resident mast cells

(2023) Shammy Raj et al.   Acta Biomaterialia

Paralog-specific signaling by IRAK1/4 maintains MyD88-independent functions in MDS/AML

(2023) Joshua Ruina Bennett et al.   BLOOD

Oral IRAK-4 Inhibitor CA-4948 Is Blood-Brain Barrier Penetrant and Has Single-Agent Activity against CNS Lymphoma and Melanoma Brain Metastases

(2023) Christina A. Von Roemeling et al.   CLINICAL CANCER RESEARCH

Developments of PROTACs technology in immune-related diseases

(2023) Chao Wang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

IRAK4 inhibition dampens pathogenic processes driving inflammatory skin diseases

(2023) Stéphanie Lavazais et al.   Science Translational Medicine

PROTAC Targeted Degradation of IRAK-4 as Potential Treatment in Cancer

(2023) Robert B. Kargbo   ACS Medicinal Chemistry Letters

PROTAC targeted protein degraders: the past is prologue

(2022) Miklós Békés et al.   NATURE REVIEWS DRUG DISCOVERY

Identification and optimisation of a pyrimidopyridone series of IRAK4 inhibitors

(2022) Iain A. Cumming et al.   BIOORGANIC & MEDICINAL CHEMISTRY

The state of the art of PROTAC technologies for drug discovery

(2022) Chao Wang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

IRAK4 Signaling Drives Resistance to Checkpoint Immunotherapy in Pancreatic Ductal Adenocarcinoma

(2022) Vikas K. Somani et al.   GASTROENTEROLOGY

Doubt cast on inflammation’s stop signals

(2022) Gunjan Sinha   SCIENCE

Discovery of 5-Aryl-2,4-diaminopyrimidine Compounds as Potent and Selective IRAK4 Inhibitors

(2022) Yan Chen et al.   ACS Medicinal Chemistry Letters

Novel Tricyclic Heteroaryl Compounds as IRAK4 Inhibitors for Treating Cancer, Autoimmune and Inflammatory Diseases

(2022) Ram W. Sabnis   ACS Medicinal Chemistry Letters

Discovery of a Highly Potent and Selective Dual PROTAC Degrader of CDK12 and CDK13

(2022) Jianzhang Yang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Novel IRAK4 Inhibitors for Treating Asthma

(2022) Ram W. Sabnis   ACS Medicinal Chemistry Letters

The IRAK4 scaffold integrates TLR4-driven TRIF and MYD88 signaling pathways

(2022) Milton Pereira et al.   Cell Reports

Oral IRAK4 inhibitor BAY-1834845 prevents acute respiratory distress syndrome

(2022) Qianqian Li et al.   BIOMEDICINE & PHARMACOTHERAPY

Bicyclic pyrimidine compounds as potent IRAK4 inhibitors

(2022) Yan Chen et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

A bibliometric analysis of PROTAC from 2001 to 2021

(2022) Deping Li et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Thienopyridinyl and Thiazolopyridinyl Compounds as IRAK4 Inhibitors

(2021) Ram W. Sabnis   ACS Medicinal Chemistry Letters

Diversity-Oriented A3-Macrocyclization for Studying Influences of Ring-Size and Shape of Cyclic Peptides: CD36 Receptor Modulators

(2021) Ragnhild G. Ohm et al.   JOURNAL OF MEDICINAL CHEMISTRY

Activation of TIR signalling boosts pattern-triggered immunity

(2021) Hainan Tian et al.   NATURE

The IRAK4 kinase inhibitor PF‐06650833 blocks inflammation in preclinical models of rheumatologic disease and in humans enrolled in a randomized clinical trial

(2021) Aaron Winkler et al.   Arthritis & Rheumatology

IRAK1 and IRAK4 as emerging therapeutic targets in hematologic malignancies

(2021) Joshua Bennett et al.   CURRENT OPINION IN HEMATOLOGY

Developments of CRBN-based PROTACs as potential therapeutic agents

(2021) Chao Wang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

The spectrum of inflammatory responses

(2021) Ruslan Medzhitov   SCIENCE

Design and synthesis of Imidazo[1,2-b]pyridazine IRAK4 inhibitors for the treatment of mutant MYD88 L265P diffuse large B-cell lymphoma

(2020) Yun Chen et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Therapeutic effects of interleukin-1 receptor-associated kinase 4 inhibitor AS2444697 on diabetic nephropathy in type 2 diabetic mice

(2020) Mitsuhiro Kondo et al.   NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY

Inflammation’s Epigenetic Footprint in Hematopoietic Stem Cells

(2020) Sarah S. Geiger et al.   Cell Stem Cell

IRAK4 inhibition: a promising strategy for treating RA joint inflammation and bone erosion

(2020) Sadiq Umar et al.   Cellular & Molecular Immunology

Proteolysis-targeting chimera (PROTAC) for targeted protein degradation and cancer therapy

(2020) Xin Li et al.   Journal of Hematology & Oncology

Chimera Induced Protein Degradation: PROTACs and Beyond

(2020) Lina Yin et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Small Molecule NF-κB Pathway Inhibitors in Clinic

(2020) Venkataramanan Ramadass et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Optimization of Nicotinamides as Potent and Selective IRAK4 Inhibitors with Efficacy in a Murine Model of Psoriasis

(2020) Satheesh Nair et al.   ACS Medicinal Chemistry Letters

Role of astroglial toll-like receptors (TLRs) in central nervous system infections, injury and neurodegenerative diseases

(2020) Lun Li et al.   BRAIN BEHAVIOR AND IMMUNITY

Discovery of CA-4948, an Orally Bioavailable IRAK4 Inhibitor for Treatment of Hematologic Malignancies

(2020) Venkateshwar Rao Gummadi et al.   ACS Medicinal Chemistry Letters

Proteolysis targeting chimera (PROTAC) in drug discovery paradigm: Recent progress and future challenges

(2020) Shenxin Zeng et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Design, Synthesis, and Biological Evaluation of IRAK4-Targeting PROTACs

(2020) Yun Chen et al.   ACS Medicinal Chemistry Letters

Structure-Based Macrocycle Design in Small-Molecule Drug Discovery and Simple Metrics To Identify Opportunities for Macrocyclization of Small-Molecule Ligands

(2019) Maxwell D. Cummings et al.   JOURNAL OF MEDICINAL CHEMISTRY

Conformational flexibility and inhibitor binding to unphosphorylated interleukin-1 receptor–associated kinase 4 (IRAK4)

(2019) Li Wang et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

U2AF1 mutations induce oncogenic IRAK4 isoforms and activate innate immune pathways in myeloid malignancies

(2019) Molly A. Smith et al.   NATURE CELL BIOLOGY

Targeting IRAK4 disrupts inflammatory pathways and delays tumor development in chronic lymphocytic leukemia

(2019) Neus Giménez et al.   LEUKEMIA

Targeting IRAK4 for Degradation with PROTACs

(2019) Joao Nunes et al.   ACS Medicinal Chemistry Letters

Overcoming adaptive therapy resistance in AML by targeting immune response pathways

(2019) Katelyn Melgar et al.   Science Translational Medicine

PROTAC Degradation of IRAK4 for the Treatment of Neurodegenerative and Cardiovascular Diseases

(2019) Robert B. Kargbo   ACS Medicinal Chemistry Letters

PROTAC Degradation of IRAK4 for the Treatment of Cancer

(2019) Robert B. Kargbo   ACS Medicinal Chemistry Letters

Discovery of a Series of 5-Azaquinazolines as Orally Efficacious IRAK4 Inhibitors Targeting MyD88L265P Mutant Diffuse Large B Cell Lymphoma

(2019) Sébastien L. Degorce et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Potent Benzolactam IRAK4 Inhibitors with Robust in Vivo Activity

(2019) Naomi S. Rajapaksa et al.   ACS Medicinal Chemistry Letters

Structure-Based Design of a Macrocyclic PROTAC

(2019) Andrea Testa et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Interleukin-1 receptor–associated kinase 4 (IRAK4) plays a dual role in myddosome formation and Toll-like receptor signaling

(2018) Dominic De Nardo et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Mechanism of dysfunction of human variants of the IRAK4 kinase and a role for its kinase activity in interleukin-1 receptor signaling

(2018) Saurav De et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

A Critical Role of the IL-1β-IL-1R Signaling Pathway in Skin Inflammation and Psoriasis Pathogenesis

(2018) Yihua Cai et al.   JOURNAL OF INVESTIGATIVE DERMATOLOGY

IRAK4 kinase activity controls Toll-like receptor–induced inflammation through the transcription factor IRF5 in primary human monocytes

(2017) Leah Cushing et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Discovery of Clinical Candidate 1-{[(2S,3S,4S)-3-Ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-7-methoxyisoquinoline-6-carboxamide (PF-06650833), a Potent, Selective Inhibitor of Interleukin-1 Receptor Associated Kinase 4 (IRAK4), by Fragment-Based Drug Design

(2017) Katherine L. Lee et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery and Optimization of Pyrrolopyrimidine Inhibitors of Interleukin-1 Receptor Associated Kinase 4 (IRAK4) for the Treatment of Mutant MYD88L265P Diffuse Large B-Cell Lymphoma

(2017) James S. Scott et al.   JOURNAL OF MEDICINAL CHEMISTRY

Peptide Macrocyclization Inspired by Non-Ribosomal Imine Natural Products

(2017) Lara R. Malins et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Selective IRAK4 Inhibition Attenuates Disease in Murine Lupus Models and Demonstrates Steroid Sparing Activity

(2016) Shailesh Dudhgaonkar et al.   JOURNAL OF IMMUNOLOGY

Recent Progress in the Molecular Recognition and Therapeutic Importance of Interleukin-1 Receptor-Associated Kinase 4

(2016) Mahesh Patra et al.   MOLECULES

Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD and Beyond

(2016) Vasiliki Michopoulos et al.   NEUROPSYCHOPHARMACOLOGY

Identification of N-(1H-pyrazol-4-yl)carboxamide inhibitors of interleukin-1 receptor associated kinase 4: Bicyclic core modifications

(2015) Jongwon Lim et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery and hit-to-lead optimization of 2,6-diaminopyrimidine inhibitors of interleukin-1 receptor-associated kinase 4

(2015) William T. McElroy et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Selective interleukin-1 receptor–associated kinase 4 inhibitors for the treatment of autoimmune disorders and lymphoid malignancy

(2015) Priscilla N. Kelly et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Inflammation's stop signals

(2015) M. Leslie   SCIENCE

Potent and Selective Amidopyrazole Inhibitors of IRAK4 That Are Efficacious in a Rodent Model of Inflammation

(2015) William T. McElroy et al.   ACS Medicinal Chemistry Letters

Discovery and Structure Enabled Synthesis of 2,6-Diaminopyrimidin-4-one IRAK4 Inhibitors

(2015) W. Michael Seganish et al.   ACS Medicinal Chemistry Letters

Identification and optimization of indolo[2,3-c]quinoline inhibitors of IRAK4

(2014) L. Nathan Tumey et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Cancer-related inflammation and treatment effectiveness

(2014) Connie I Diakos et al.   LANCET ONCOLOGY

Renoprotective effects of novel interleukin-1 receptor-associated kinase 4 inhibitor AS2444697 through anti-inflammatory action in 5/6 nephrectomized rats

(2014) Mitsuhiro Kondo et al.   NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY

Innate Immune Interleukin-1 Receptor–Associated Kinase 4 Exacerbates Viral Myocarditis by Reducing CCR5 + CD11b + Monocyte Migration and Impairing Interferon Production

(2013) Alan Valaperti et al.   CIRCULATION

Differential IRAK signaling in hematologic malignancies

(2013) Garrett W. Rhyasen et al.   EXPERIMENTAL HEMATOLOGY

Inflammation's Yin-Yang

(2013) K. Mueller   SCIENCE

IRAK-4 Inhibitors for Inflammation

(2009) Zhulun Wang et al.   CURRENT TOPICS IN MEDICINAL CHEMISTRY

IRAK-4 inhibitors. Part 1: A series of amides

(2008) George M. Buckley et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

IRAK-4 inhibitors. Part II: A structure-based assessment of imidazo[1,2-a]pyridine binding

(2008) George M. Buckley et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Design, Synthesis, and In Vitro Activity of Peptidomimetic Inhibitors of Myeloid Differentiation Factor 88

(2008) Nicola Fantò et al.   JOURNAL OF MEDICINAL CHEMISTRY

Cancer-related inflammation

(2008) Alberto Mantovani et al.   NATURE