Araxes Pharma LLC

Intellikine LLC

Kura Oncology, Inc.

Infinity Pharmaceuticals, Inc.

University of Michigan

Anadys Pharmaceuticals, Inc.

Kumquat Biosciences Inc.

Janssen Biotech, Inc.

University of California

Pfizer Corporation

Millennium Pharmaceuticals Limited

Itellikine LLC

Takeda Pharmaceutical Company Limited

Liansheng Li

Pingda Ren

Yi Liu

Jun Feng

Katrina Chan

Tao Wu

Troy Edward Wilson

Yuan Liu

Yun Long

Alfredo C Castro

Catherine Anne Evans

Yi Wang

Daniel A Snyder

Christian Rommel

Jolanta Grembecka

Tomasz Cierpicki

Dmitry Borkin

Martin R Tremblay

Tao Liu

Andre Lescarbeau

Somarajannair Janardanannair

Szymon Klossowski

Simon F Campbell

Stephen Evan Webber

Chinh Viet Tran

Frank Ruebsam

Zhiyong Chen

Michael Martin

Jonathan Pollock

Peter Scott Dragovich

Xiuwen Zhu

David J Kucera

Douglas Eric Murphy

Zhongxiang Sun

Martin Tran

Zhimin Zhu

Duxin Sun

Xiaoming Li

Baogen Wu

Hongzhi Miao

Matthew Patricelli

Yuefen Zhou

Siling Zhao

Kevan M Shokat

Neelakandha S Mani

Jason Gustaf Lewis

Mikhail Fedorovich Gordeev

Xiaohu Deng

Andrew Gaheem Hsieh

Brett D Allison

Jimmy T Liang

Sampath Kumar Anandan

Zachary S Sales

David Ellis

Davide Ruggero

Hardwin O'Dowd

Beth Apsel

Jingchuan Zhang, I

Alana K Borum

Ulf Peters

David Fruman

Morris Feldman

David Pearce

Matthew Janes

Francis Burrows

Matthew Robert Janes

Linda V Kessler

Matthew Peter Patricelli

Yun Oliver Long

Simon Fraser Campbell

David John Kucera

Douglas E Murphy

Martin T Tran

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

The present disclosure provides compounds and pharmaceutically acceptable salt thereof, and methods of using the same. The compounds and methods have a range of utilities as therapeutics, diagnostics, and research tools. In particular, the subject compositions and methods are useful for reducing signaling output of oncogenic proteins.

Heterocyclic compounds and uses thereof

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

The present disclosure provides compounds and pharmaceutically acceptable salts thereof, and methods of using the same. The compounds and methods have a range of utilities as therapeutics, diagnostics, and research tools. In particular, the subject compositions and methods are useful for reducing signaling output of oncogenic 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, 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

The present disclosure provides compounds and pharmaceutically acceptable salts thereof, and methods of using the same. The compounds and methods have a range of utilities as therapeutics, diagnostics, and research tools. In particular, the subject compositions and methods are useful for reducing signaling output of certain oncogenic proteins.

The present disclosure provides methods for treating hematological malignancies and Ewings sarcoma using menin inhibitors. Compositions for use in these methods are also provided.

Methods for treating hematological malignancies and Ewing's sarcoma

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

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

The present disclosure provides methods of inhibiting the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins with compositions of Formula (II-A). The methods 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. Compositions of Formula (II-A) for use in these methods are also provided. 

Substituted inhibitors of menin-MLL and methods of use

The present disclosure provides methods of inhibiting the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins. The methods 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. Compositions for use in these methods are also provided.

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 compounds of Formula (I-A) for inhibiting the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins. The compounds 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. 

Bridged bicyclic inhibitors of menin-MLL and methods of use

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San Diego, CA, United States of America

Liansheng Li