Millennium Pharmaceuticals Limited

Innate Tumor Immunity, Inc.

Celgene Avilomics Research, Inc.

Novartis Ag

Gilead Apollo, LLC

Kyowa Hakko Kirin Co., Limited

Avila Therapeutics, Inc.

Kyowa Hakko Kogyo Co., Ltd.

Celgene Car LLC

Microdose Therapeutx, Inc.

Nanotherapeutics, Inc.

Cystic Fibrosis Foundation Therapeutics, Inc.

Cytopathfinder, Inc.

Novartis Inflammasome Research, Inc.

Shomir Ghosh

William R Roush

Gary D Glick

Arthur F Kluge

Russell Colyn Petter

Juswinder Singh

Kenneth Gordon Carson

Amy M Elder

Edward James Olhava

Geraldine C B Harriman

Dong-Ming Shen

Richland Wayne Tester

Shankar Venkatraman

Jason David Katz

Hans Martin Seidel

Deqiang Niu

Jeremy Robert Greenwood

Jay R Luly

Lixin Qiao

Geraldine C Harriman

David Guenther Winkler

Yoshisuke Nakasato

Francois Soucy

Etsuo Ohshima

Daniel O'Malley

Prakash Raman

Silvana Marcel Leit De Moradei

Luigi Franchi

Anthony William Opipari, Jr

Karen M Mattia

Qing Ye

Kevin Sprott

Tracy J Jenkins

Bing Guan

Roger A Jones

Mingshi Dai

Charles A Minor

Ashvinikumar V Gavai

Gang Li

Sean J Harrison

Douglas F Burdi

Robert A Bennett

Scott Hunter Watterson

David K Williams

Roy R Lobb

Christine M Tarby

Zhendong Zhu

Patrice Gill

Hua Gong

Christelle C Renou

Sian Griffiths

Zhongguo Wang

Sharon Shacham

Jian Lin

Steven P Seitz

Prasanna Sivaprakasam

Dominic J Reynolds

Yong Zhang

Vincent Jacques

Urszula Slomczynska

William P Haakenson, Jr

Jay A Markwalder

Yael Marantz

Barry J Shortt

Dongli Chen

Boaz Inbal

Mercedes Lobera

Carmen M Baldino

Zhaoda Zhang

Pradyumna Mohanty

Andrew Forrest Donnell

Steffi Koerner

Jeffrey Michael Stein

Merav Fichman

Phoebe Chiang

Frederick A Hicks

Jeremy D Little

Efrat Ben-Zeev

Lazlo Varady

Thomas Andreas Waldbach

Gali Golan

Jennifer Lynn Bennett

Karen C Fitzsimmons

Rosa E Melendez

Dan P Cook

Roger Jones

Anthony William Opipari Jr

Anthony William Opipari

William P Haakenson

Urszula J Slomczynska

Geraldine CB Harriman

Etsuo Oshima

In one aspect, compounds of Formula AA, or a pharmaceutically acceptable salt thereof, are featured: or a pharmaceutically acceptable salt thereof, wherein the variables shown in Formula A can be as defined anywhere herein.

Compounds and compositions for treating conditions associated with NLRP activity

This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that modulate (e.g., agonizes or partially agonizes) NLRP3 that are useful, e.g., for treating a condition, disease or disorder in which an increase in NLRP3 signaling may correct a deficiency in innate immune activity (e.g., a condition, disease or disorder associated with an insufficient immune response) that contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). This disclosure also features compositions as well as other methods of using and making the same.

NLRP3 modulators

The present invention provides compounds of Formula (I): wherein all of the variables are as defined herein. These compounds are modulators of NLRP3, which may be used as medicaments for the treatment of proliferative disorders, such as cancer in a subject (e.g., a human).

In one aspect, compounds of Formula AA, or a pharmaceutically acceptable salt thereof, are featured:

In one aspect, compounds of Formulae (I) and (II), or pharmaceutically acceptable salts thereof, are featured; Formula (I), Formula (II) or a pharmaceutically acceptable salt thereof, wherein the variables shown in Formulae (I) and (II) can be as defined anywhere herein.

In one aspect, compounds of Formula AA, or a pharmaceutically acceptable salt thereof, are featured: wherein the variables shown in Formula AA can be as defined anywhere herein. Compounds AA are modulators of NLRP1 and/or NLRP3

Sulphonamides and compositions thereof for treating conditions associated with NLRP activity

In one aspect, compounds of Formulae (I) and (II), or pharmaceutically acceptable salts thereof, are featured: Formulae (I) and (II), wherein the variables shown in Formulae (I) and (II) can be as defined anywhere herein. 

This disclosure features chemical entities (e.g., a compound that modulates (e.g., agonizes) Stimulator of Interferon Genes (STING), or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that are useful, e.g., for treating a condition, disease or disorder in which a decrease or increase in STING activity (e.g., a decrease, e.g., a condition, disease or disorder associated with repressed or impaired STING signaling) contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). This disclosure also features compositions as well as other methods of using and making the same.

Compounds and compositions for treating conditions associated with sting activity

In one aspect, compounds of Formula A, or a pharmaceutically acceptable salt thereof, are featured, or a pharmaceutically acceptable salt thereof, wherein the variables shown in Formula A can be as defined anywhere herein. 

In one aspect, compounds of Formula AA, or a pharmaceutically acceptable salt thereof, are featured. The variables shown in Formula AA are as defined in the claims. The compounds of formula AA are NLRP3 activity modulators and, as such, can be used in the treatment of metabolic disorders (e.g. Type 2 diabetes, atherosclerosis, obesity or gout), a disease of the central nervous system (e.g. Alzheimer's disease, multiple sclerosis, Amyotrophic Lateral Sclerosis or Parkinson's disease), lung disease (e.g. asthma, COPD or pulmonary idiopathic fibrosis), liver disease (e.g. NASH syndrome, viral hepatitis or cirrhosis), pancreatic disease (e.g. acute pancreatitis or chronic pancreatitis), kidney disease (e.g. acute kidney injury or chronic kidney injury), intestinal disease (e.g. Crohn's disease or Ulcerative Colitis), skin disease (e.g. psoriasis), musculoskeletal disease (e.g. scleroderma), a vessel disorder (e.g. giant cell arteritis), a disorder of the bones (e.g. osteoarthritis, osteoporosis or osteopetrosis disorders), eye disease (e.g. glaucoma or macular degeneration), a disease caused by viral infection (e.g. HIV or AIDS), an autoimmune disease (e.g. Rheumatoid Arthritis, Systemic Lupus Erythematosus or Autoimmune Thyroiditis), cancer or aging. 

The present invention provides compounds of Formula (I): (I) wherein all of the variables are as defined herein. These compounds are modulators of NLRP3, which may be used as medicaments for the treatment of proliferative disorders, such as cancer in a subject (e.g., a human). 

In one aspect, compounds of Formulae (I) and (II), or pharmaceutically acceptable salts thereof, are featured; Formula (I), Formula (II) or a pharmaceutically acceptable salt thereof, wherein the variables shown in Formulae (I) and (II) can be as defined anywhere herein. 

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Brookline, MA, United States of America

Shomir Ghosh