Overcoming Preclinical Safety Obstacles to Discover (S)-N-((1,2,3,5,6,7-Hexahydro-s-indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonamide (GDC-2394): A Potent and Selective NLRP3 Inhibitor

Structure of the NLRP3 decamer bound to the cytokine release inhibitor CRID3

(2022) Inga V. Hochheiser et al.   NATURE

Comparison of logP and logD correction models trained with public and proprietary data sets

(2022) Ignacio Aliagas et al.   JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN

Structural basis for the oligomerization-mediated regulation of NLRP3 inflammasome activation

(2022) Umeharu Ohto et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NLRP3 cages revealed by full-length mouse NLRP3 structure control pathway activation

(2021) Liudmila Andreeva et al.   CELL

Crystal Structure of NLRP3 NACHT Domain With an Inhibitor Defines Mechanism of Inflammasome Inhibition

(2021) Carien Dekker et al.   JOURNAL OF MOLECULAR BIOLOGY

Prediction of active human dose: learnings from 20 years of Merck KGaA experience, illustrated by case studies

(2020) Sheila Annie Peters et al.   DRUG DISCOVERY TODAY

The NLRP1 and CARD8 inflammasomes

(2020) Cornelius Y. Taabazuing et al.   IMMUNOLOGICAL REVIEWS

Improving the Accuracy of Predicted Human Pharmacokinetics: Lessons Learned from the AstraZeneca Drug Pipeline Over Two Decades

(2020) Michael Davies et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition

(2019) Rebecca C. Coll et al.   Nature Chemical Biology

MCC950 closes the active conformation of NLRP3 to an inactive state

(2019) Ana Tapia-Abellán et al.   Nature Chemical Biology

Structural mechanism for NEK7-licensed activation of NLRP3 inflammasome

(2019) Humayun Sharif et al.   NATURE

MCC950/CRID3 potently targets the NACHT domain of wild-type NLRP3 but not disease-associated mutants for inflammasome inhibition

(2019) Lieselotte Vande Walle et al.   PLOS BIOLOGY

Targeting the NLRP3 inflammasome in inflammatory diseases

(2018) Matthew S. J. Mangan et al.   NATURE REVIEWS DRUG DISCOVERY

Evaluating the Utility of Canine Mdr1 Knockout Madin-Darby Canine Kidney I Cells in Permeability Screening and Efflux Substrate Determination

(2018) Eugene C Chen et al.   MOLECULAR PHARMACEUTICS

NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice

(2017) Auvro R. Mridha et al.   JOURNAL OF HEPATOLOGY

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

Efficacy and Pharmacology of the NLRP3 Inflammasome Inhibitor CP-456,773 (CRID3) in Murine Models of Dermal and Pulmonary Inflammation

(2016) Michael J. Primiano et al.   JOURNAL OF IMMUNOLOGY

Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling

(2015) Nobuhiko Kayagaki et al.   NATURE

A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases

(2015) Rebecca C Coll et al.   NATURE MEDICINE

Inflammasomes: mechanism of action, role in disease and therapeutics

(2015) Haitao Guo et al.   NATURE MEDICINE

Setting Clinical Exposure Levels of Concern for Drug-Induced Liver Injury (DILI) Using Mechanisticin vitroAssays

(2015) Falgun Shah et al.   TOXICOLOGICAL SCIENCES

The role of ligand efficiency metrics in drug discovery

(2014) Andrew L. Hopkins et al.   NATURE REVIEWS DRUG DISCOVERY

High lipophilicity and high daily dose of oral medications are associated with significant risk for drug-induced liver injury

(2012) Minjun Chen et al.   HEPATOLOGY

Cholesterol Crystals Activate the NLRP3 Inflammasome in Human Macrophages: A Novel Link between Cholesterol Metabolism and Inflammation

(2010) Kristiina Rajamäki et al.   PLoS One