Araxes Pharma LLC

Takeda Pharmaceutical Company Limited

Kura Oncology, Inc.

Takeda San Diego, Inc.

University of Michigan

Pfizer Corporation

Janssen Biotech, Inc.

Erasca, Inc.

Novo Nordisk A/s

Agouron Pharmaceuticals, Inc.

Takeda Pharmaceutical Company Limied

Takeda California, Inc.

Jun Feng

Yi Liu

Pingda Ren

Liansheng Li

Tao Wu

Yuan Liu

Stephen L Gwaltney

Yun Long

Jeffrey Alan Stafford

Zhiyuan Zhang

Michael Brennan Wallace

Stephen W Kaldor

Paul Isbester

Grant Jackson Palmer

Bruce Joseph Elder

Luckner Gerard Ulysse

Mingnam Tang

Jonathon Stuart Salsbury

Yi Wang

Jolanta Grembecka

Tomasz Cierpicki

Dmitry Borkin

Jonathan Pollock

Zacharia S Cheruvallath

Joanne Miura

Mark Sabat

Prasuna Guntupalli

Yufeng Hong

Sheldon Cao

Jean-Michel Andre Vernier

Xiao-Yi Xiao

Benjamin Jones

Duxin Sun

Haitao Li

Mark Brian Anderson

Szymon Klossowski

Ping Chen

Ved Prakash Pathak

Robert J Skene

Hongzhi Miao

Eileen Valenzuela Tompkins

Lance Christopher Christie

Ranjan Jagath Rajapakse

Haxia Wang

Marcos Gonzalez-Lopez

Nicholas A Isley

Zhlyuan Zhang

Jesper F Lau

Min Teng

Peter Madsen

Eric T Sun

Christopher McBride

John David Lawson

Christian Klarner Sams

Vlad Edward Gregor

Michael Bruno Plewe

Betty Lam

Lars Naerum

Beverly Lynn Wolgast

Sean Timothy Murphy

Anthony Lai Ling

Shenghua Shi

Sripathy Venkatraman

David J Hosfield

Javier Gonzalez

Bingidimi Itute Mobele

Quyen-Quyen Thuy Do

Michael David Johnson

Paul R Brodfuehrer

Mallareddy Komandla

Richard S Fornicola

Atsuo Kuki

Ulla Grove Sidelmann

Maxwell M Reeve

Lotte Bjerre Knudsen

Dan Kiel

Philip Erickson

Huong-Thu Ton-Nu

Haresh Vazir

Kimberly Ann Teston

Alana K Borum

David J Hossfield

Paul R Brodfuahrer

Philip B Kisanga

Jonathan S Salsbury

ZhiYuan Zhang

Paul K Isbester

Sheldon X Cao

Yun Oliver Long

Stephen L Ii Gwaltney

Luckner G c/o Albany Molecular Research Inc Ulysee

Jonathon S c/o Albany Molecular Research Inc Salsbury

Grant J c/o Albany Molecular Research Inc Palmer

Bruce J c/o Albany Molecular Research Inc Elder

Paul K c/o Albany Molecular Research Inc Isbester

Ii Stephen L Gwaltney

Irreversible inhibitors of G12C mutant K-Ras protein are provided. Also disclosed are methods to modulate the activity of G12C mutant K-Ras protein and methods of treatment of disorders mediated by G12C mutant K-Ras protein.

Covalent inhibitors of KRAS G12C

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have one of the following structures (I), (II) or (III): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein R, R, R, R, R, R, R, R, R, R, R, A, B, G, G, L, L, m, m, n, x, y, X and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

Substituted quinazoline compounds and methods of use thereof

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, have the following structure: wherein A, L, L, Q, R, R, R, R, R, R, R, R, Y, and Z are as exemplified herein. Pharmaceutical compositions comprising such compounds, methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, and methods associated with preparation of such compounds are also provided.

Substituted piperazines as inhibitors of KRAS G12C

Tricyclic pyridones and pyrimidones

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, stereoisomer, isotopic form or prodrug thereof, wherein R, L, L, L, A, A, A, A, G, G, E, W, X, Y, Z, m, and n are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

Heterocyclic spiro compounds and methods of use thereof for the treatment of cancer

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R, R, R, R, R, R, G, G, L, L, m, m, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

Substituted quinazolines as inhibitors of KRAS G12C

Compounds with KRAS G12C inhibitory active are disclosed and methods of using the same to treat a cancer comprising a K-Ras G12C mutation.

The present disclosure provides compounds and methods for inhibiting the interaction of menin with its upstream or downstream signaling molecules including but not limited to MLL1, MLL2 and MLL-fusion oncoproteins. Compounds of the disclosure may be used in methods for the treatment of a wide variety of cancers and other diseases associated with one or more of MLL1, MLL2, MLL fusion proteins, and menin.

Thienopyrimidine and thienopyridine compounds and methods of use thereof

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, stereoisomer, isotopic form or prodrug thereof, wherein R, R, R, R, R, R, R, R, R, L, L, E, mand mare as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided. 

Quinazoline derivatives as modulators of mutant KRAS, HRAS or NRAS

The present disclosure provides compositions and methods of use to inhibit the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins. The compositions and methods of use are useful for the treatment of leukemia, solid cancers, diabetes and other diseases dependent on activity of MLL1, MLL2, MLL fusion proteins, and/or menin.

Methods and compositions for inhibiting the interaction of menin with MLL proteins

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, stereoisomer, isotopic form or prodrug thereof, wherein R, R, R, R, R, R, R, R, R, L, L, L, E, m, mand * are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

Covalent inhibitors of KRAS

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I) or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein B, Z, R, R, R, R, L, Land E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided. 

Benzothiophene and benzothiazole compounds and methods of use thereof

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, isotopic form or stereoisomer thereof, wherein A is a five-membered heteroaryl comprising 1 or 2 non-adjacent heteroatoms, inclusive of X and Y; W, X, Y, Z, L, L, E, R, RRand the dotted circle are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and compounds for use in methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided. Preferred compounds are e.g. 1-(3-(6-(3-hydroxynaphthalen-1-yl)benzofuran-2-yl)azetidin-1yl)prop-2-en-1-one derivatives and related compounds such as e.g. the corresponding derivatives with e.g. a benzoimidazole, indole, benzooxazole, imidazopyridine or imidazole core structure, substituted on ring A by e.g. azetidine, pyrrolidine, azepane or bicyclopentane-amine (L) each substituted by e.g. propenone (E), and the core structure substituted on the six-membered ring with e.g. 3-hydroxynaphthalene or indazole or hydroxy-, alkoxy- and/or fluoro-substituted phenyl (R). 

1-(3-(6-(3-hydroxynaphthalen-1-yl)benzofuran-2-yl)azetidin-1 yl)prop-2-en-1-one derivatives and similar compounds as KRAS G12C modulators for treating cancer

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): (I) or a pharmaceutically acceptable salt, isotopic form, stereoisomer or prodrug thereof, wherein A, B, X, R1, R2a, R2b, R2c, L, L1 and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided. 

Fused bicyclic benzoheteroaromatic compounds and methods of use thereof

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): (Formula (I)) or a pharmaceutically acceptable salt, stereoisomer thereof, wherein G, Y, R, R, R, R, R, L, Land E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided. Preferred compounds are quinazoline and quinazolinone derivatives and in particular 1-(6-(3-hydroxynaphthalen-1-yl)quinazolin-2-yl)azetidin-1-yl)prop-2-en-1-one derivatives and similar compounds. 

Substituted quinazoline and quinazolinone compounds and methods of use thereof

Growing community of inventors

San Diego, CA, United States of America

Jun Feng