Profiling of small‐molecule necroptosis inhibitors based on the subpockets of kinase–ligand interactions

Targeting Necroptosis as a Promising Therapy for Alzheimer’s Disease

(2022) Wenli Zhao et al.   ACS Chemical Neuroscience

Principles of Kinase Allosteric Inhibition and Pocket Validation

(2022) Yue Pan et al.   JOURNAL OF MEDICINAL CHEMISTRY

Reversible lysine-targeted probes reveal residence time-based kinase selectivity

(2022) Tangpo Yang et al.   Nature Chemical Biology

Kinase-targeting small-molecule inhibitors and emerging bifunctional molecules

(2022) Georg L. Goebel et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Orally effective FDA-approved protein kinase targeted covalent inhibitors (TCIs)

(2021) Robert Roskoski   PHARMACOLOGICAL RESEARCH

Ring Closure Strategy Leads to Potent RIPK3 Inhibitors

(2021) Shuwei Wu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Structure-based optimizations of a necroptosis inhibitor (SZM594) as novel protective agents of acute lung injury

(2021) Lijuan Xu et al.   CHINESE CHEMICAL LETTERS

Structure-based bioisosterism design of thio-benzoxazepinones as novel necroptosis inhibitors

(2021) Chunnian Xia et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Hydrophobic and polar interactions of FDA-approved small molecule protein kinase inhibitors with their target enzymes

(2021) Robert Roskoski   PHARMACOLOGICAL RESEARCH

Discovery of a cooperative mode of inhibiting RIPK1 kinase

(2021) Huyan Meng et al.   Cell Discovery

Potent and Selective RIPK1 Inhibitors Targeting Dual‐Pockets for the Treatment of Systemic Inflammatory Response Syndrome and Sepsis

(2021) Xiangbo Yang et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Human RIPK3 maintains MLKL in an inactive conformation prior to cell death by necroptosis

(2021) Yanxiang Meng et al.   Nature Communications

Ligand-based substituent-anchoring design of selective receptor-interacting protein kinase 1 necroptosis inhibitors for ulcerative colitis therapy

(2021) Jing Zhu et al.   Acta Pharmaceutica Sinica B

RIP1 kinase activity is critical for skin inflammation but not for viral propagation

(2020) Joshua D. Webster et al.   JOURNAL OF LEUKOCYTE BIOLOGY

Inhibition of keratinocyte necroptosis mediated by RIPK1/RIPK3/MLKL provides a protective effect against psoriatic inflammation

(2020) Xiaoru Duan et al.   Cell Death & Disease

Targeting necroptosis in anticancer therapy: mechanisms and modulators

(2020) Ying Wu et al.   Acta Pharmaceutica Sinica B

Radiosensitization of human pancreatic cancer by piperlongumine analogues

(2020) Hao Ma et al.   CHINESE CHEMICAL LETTERS

KLIFS: an overhaul after the first 5 years of supporting kinase research

(2020) Georgi K Kanev et al.   NUCLEIC ACIDS RESEARCH

Inhibitors of RIP1 kinase: a patent review (2016–present)

(2020) Philip A. Harris   EXPERT OPINION ON THERAPEUTIC PATENTS

Discovery of a Potent RIPK3 Inhibitor for the Amelioration of Necroptosis-Associated Inflammatory Injury

(2020) Kaijiang Xia et al.   Frontiers in Cell and Developmental Biology

Identification of a novel class of RIP1/RIP3 dual inhibitors that impede cell death and inflammation in mouse abdominal aortic aneurysm models

(2019) Ting Zhou et al.   Cell Death & Disease

Identification of the Raf kinase inhibitor TAK‐632 and its analogues as potent inhibitors of necroptosis by targeting RIPK1 and RIPK3

(2019) Xiaofei Chen et al.   BRITISH JOURNAL OF PHARMACOLOGY

RIP1 inhibition blocks inflammatory diseases but not tumor growth or metastases

(2019) Snahel Patel et al.   CELL DEATH AND DIFFERENTIATION

Discovery and Lead-Optimization of 4,5-Dihydropyrazoles as Mono-Kinase Selective, Orally Bioavailable and Efficacious Inhibitors of Receptor Interacting Protein 1 (RIP1) Kinase

(2019) Philip A. Harris et al.   JOURNAL OF MEDICINAL CHEMISTRY

N-(7-Cyano-6-(4-fluoro-3-(2-(3-(trifluoromethyl)phenyl)acetamido)phenoxy)benzo[d]thiazol-2-yl)cyclopropanecarboxamide (TAK-632) Analogues as Novel Necroptosis Inhibitors by Targeting Receptor-Interacting Protein Kinase 3 (RIPK3): Synthesis, Structure–Activity Relationships, and in Vivo Efficacy

(2019) Hao Zhang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Assessing Lysine and Cysteine Reactivities for Designing Targeted Covalent Kinase Inhibitors

(2019) Ruibin Liu et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Identification of RIPK3 Type II Inhibitors Using High-Throughput Mechanistic Studies in Hit Triage

(2019) Amy C. Hart et al.   ACS Medicinal Chemistry Letters

Identification of a RIP1 Kinase Inhibitor Clinical Candidate (GSK3145095) for the Treatment of Pancreatic Cancer

(2019) Philip A. Harris et al.   ACS Medicinal Chemistry Letters

Potent and selective inhibitors of receptor-interacting protein kinase 1 that lack an aromatic back pocket group

(2019) Gregory L. Hamilton et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery of potent necroptosis inhibitors targeting RIPK1 kinase activity for the treatment of inflammatory disorder and cancer metastasis

(2019) Jue Hou et al.   Cell Death & Disease

Small-Molecule Inhibitors of Necroptosis: Current Status and Perspectives

(2019) Chunlin Zhuang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Activation loop targeting strategy for design of receptor-interacting protein kinase 2 (RIPK2) inhibitors

(2018) Chalada Suebsuwong et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Tozasertib Analogues as Inhibitors of Necroptotic Cell Death

(2018) Sam Hofmans et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of 7-Oxo-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridine Derivatives as Potent, Orally Available, and Brain-Penetrating Receptor Interacting Protein 1 (RIP1) Kinase Inhibitors: Analysis of Structure–Kinetic Relationships

(2018) Masato Yoshikawa et al.   JOURNAL OF MEDICINAL CHEMISTRY

Kinase inhibitors: the road ahead

(2018) Fleur M. Ferguson et al.   NATURE REVIEWS DRUG DISCOVERY

Crystal Structure of Ripk4 Reveals Dimerization-Dependent Kinase Activity

(2018) Christine S. Huang et al.   STRUCTURE

RIPK1-dependent cell death: a novel target of the Aurora kinase inhibitor Tozasertib (VX-680)

(2018) Sofie Martens et al.   Cell Death & Disease

Phenytoin inhibits necroptosis

(2018) Anne von Mässenhausen et al.   Cell Death & Disease

Neuroprotective Effects of DTIO, A Novel Analog of Nec-1, in Acute and Chronic Stages After Ischemic Stroke

(2018) Wei Li et al.   NEUROSCIENCE

RIP1 Kinase Drives Macrophage-Mediated Adaptive Immune Tolerance in Pancreatic Cancer

(2018) Wei Wang et al.   CANCER CELL

Identification of 5-(2,3-Dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine Derivatives as a New Class of Receptor-Interacting Protein Kinase 1 (RIPK1) Inhibitors, Which Showed Potent Activity in a Tumor Metastasis Model

(2018) Yueshan Li et al.   JOURNAL OF MEDICINAL CHEMISTRY

Autophagy protein ATG16L1 prevents necroptosis in the intestinal epithelium

(2017) Yu Matsuzawa-Ishimoto et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases

(2017) Philip A. Harris et al.   JOURNAL OF MEDICINAL CHEMISTRY

Exploiting non-covalent π interactions for catalyst design

(2017) Andrew J. Neel et al.   NATURE

Allosteric MEK1/2 inhibitors including cobimetanib and trametinib in the treatment of cutaneous melanomas

(2017) Robert Roskoski   PHARMACOLOGICAL RESEARCH

RIPK1 mediates a disease-associated microglial response in Alzheimer’s disease

(2017) Dimitry Ofengeim et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

RIPK3 deficiency or catalytically inactive RIPK1 provides greater benefit than MLKL deficiency in mouse models of inflammation and tissue injury

(2016) K Newton et al.   CELL DEATH AND DIFFERENTIATION

Experimental Binding Energies in Supramolecular Complexes

(2016) Frank Biedermann et al.   CHEMICAL REVIEWS

DNA-Encoded Library Screening Identifies Benzo[b][1,4]oxazepin-4-ones as Highly Potent and Monoselective Receptor Interacting Protein 1 Kinase Inhibitors

(2016) Philip A. Harris et al.   JOURNAL OF MEDICINAL CHEMISTRY

Classification of small molecule protein kinase inhibitors based upon the structures of their drug-enzyme complexes

(2016) Robert Roskoski   PHARMACOLOGICAL RESEARCH

RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS

(2016) Yasushi Ito et al.   SCIENCE

Inflammatory Signaling by NOD-RIPK2 Is Inhibited by Clinically Relevant Type II Kinase Inhibitors

(2015) Peter Canning et al.   CHEMISTRY & BIOLOGY

The diverse role of RIP kinases in necroptosis and inflammation

(2015) John Silke et al.   NATURE IMMUNOLOGY

A cellular screen identifies ponatinib and pazopanib as inhibitors of necroptosis

(2015) A Fauster et al.   Cell Death & Disease

Structure Guided Design of Potent and Selective Ponatinib-Based Hybrid Inhibitors for RIPK1

(2015) Malek Najjar et al.   Cell Reports

RIP3 Induces Apoptosis Independent of Pronecrotic Kinase Activity

(2014) Pratyusha Mandal et al.   MOLECULAR CELL

Necroptosis

(2014) Andreas Linkermann et al.   NEW ENGLAND JOURNAL OF MEDICINE

The B-RafV600E inhibitor dabrafenib selectively inhibits RIP3 and alleviates acetaminophen-induced liver injury

(2014) J-X Li et al.   Cell Death & Disease

A novel necroptosis inhibitor—necrostatin-21 and its SAR study

(2013) Zhijie Wu et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Toll-like Receptor 3-mediated Necrosis via TRIF, RIP3, and MLKL

(2013) William J. Kaiser et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

KLIFS: A Knowledge-Based Structural Database To Navigate Kinase–Ligand Interaction Space

(2013) Oscar P. J. van Linden et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of a Selective Kinase Inhibitor (TAK-632) Targeting Pan-RAF Inhibition: Design, Synthesis, and Biological Evaluation of C-7-Substituted 1,3-Benzothiazole Derivatives

(2013) Masanori Okaniwa et al.   JOURNAL OF MEDICINAL CHEMISTRY

The ErbB/HER family of protein-tyrosine kinases and cancer

(2013) Robert Roskoski   PHARMACOLOGICAL RESEARCH

Structural Basis of RIP1 Inhibition by Necrostatins

(2013) Tian Xie et al.   STRUCTURE

Discovery of Small Molecule RIP1 Kinase Inhibitors for the Treatment of Pathologies Associated with Necroptosis

(2013) Philip A. Harris et al.   ACS Medicinal Chemistry Letters

Deciphering the Structural Basis of Eukaryotic Protein Kinase Regulation

(2013) Hiruy S. Meharena et al.   PLOS BIOLOGY

Strategies for the Selective Regulation of Kinases with Allosteric Modulators: Exploiting Exclusive Structural Features

(2012) Zhizhou Fang et al.   ACS Chemical Biology

Optimization of tricyclic Nec-3 necroptosis inhibitors for in vitro liver microsomal stability

(2012) Sungwoon Choi et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

New Directions in Targeting Protein Kinases: Focusing Upon True Allosteric and Bivalent Inhibitors

(2012) Vandana Lamba et al.   CURRENT PHARMACEUTICAL DESIGN

Rip1 (Receptor-interacting protein kinase 1) mediates necroptosis and contributes to renal ischemia/reperfusion injury

(2012) Andreas Linkermann et al.   KIDNEY INTERNATIONAL

Many stimuli pull the necrotic trigger, an overview

(2011) N Vanlangenakker et al.   CELL DEATH AND DIFFERENTIATION

The Adaptor Protein FADD Protects Epidermal Keratinocytes from Necroptosis In Vivo and Prevents Skin Inflammation

(2011) Marion C. Bonnet et al.   IMMUNITY

Comprehensive analysis of kinase inhibitor selectivity

(2011) Mindy I Davis et al.   NATURE BIOTECHNOLOGY

Necroptosis as an alternative form of programmed cell death

(2010) Dana E Christofferson et al.   CURRENT OPINION IN CELL BIOLOGY

AP24534, a Pan-BCR-ABL Inhibitor for Chronic Myeloid Leukemia, Potently Inhibits the T315I Mutant and Overcomes Mutation-Based Resistance

(2009) Thomas O'Hare et al.   CANCER CELL

Structure–activity relationship and liver microsome stability studies of pyrrole necroptosis inhibitors

(2008) Xin Teng et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Structure–activity relationship study of a novel necroptosis inhibitor, necrostatin-7

(2008) Weihong Zheng et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

A helix scaffold for the assembly of active protein kinases

(2008) A. P. Kornev et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Analogous regulatory sites within the αC-β4 loop regions of ZAP-70 tyrosine kinase and AGC kinases

(2007) Natarajan Kannan et al.   BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS