Ra Pharmaceuticals, Inc.

Merck Sharp + Dohme Corp.

Massachusetts Institute of Technology

University of Illinois

Agency for Science, Technology and Research

Msd International Gmbh (singapore Branch)

Nicolas Cedric Boyer

Alonso Ricardo

Zhong Ma

Sookhee Nicole Ha

Douglas A Treco

Daniel Elbaum

Thomas Joseph Tucker

Elisabetta Bianchi

Yusheng Xiong

Zhaolin Wang

Hong Zheng

Ping Ye

Kristopher Josephson

Nathan Ezekiel Nims

Eberhard Schneider

Peter Wagner

Angela Dawn Kerekes

Raffaele Ingenito

Aurash Shahripour

Gregor Schurmann

Hyewon Youm

Danila Branca

Chengwei Wu

Paul Anderson

Willy Costantini

Joseph R Stringer

Derek M LaPlaca

Paul Joseph Hergenrother

Ketki Ashok Dhamnaskar

Mohammad Movassaghi

Karen C Morrison

Justin Kim

Eric J Gilbert

Mark W Embrey

Michelle Denise Hoarty

Alessia Santoprete

Immacolata Conte

Stefania Colarusso

Roberto Costante

Michelle Denise Arata

Tomi K Sawyer

Chunhui Huang

Charles William Johannes

Tsz Ying Yuen

Yili Sun

Rohit Vyasamneni

Jonathan C Blain

Kelli Jette

Michael B Garrigou

Pietro Aronica

Srinivasaraghavan Kannan

Anthony W Partridge

Derek M Laplaca

The invention provides compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein the variables are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12D mutant of Kirsten rat sarcoma (K-Ras) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

Macrocyclic peptides as potent inhibitors of K-RAS G12D mutant

Provided herein are cyclic polypeptide compounds that can, e.g., bind specifically to human proprotein convertase subtilisin/kexin type 9 (PCSK9) and optionally also inhibit interaction between human PCSK9 and human low density lipoprotein receptor (LDLR), and pharmaceutical compositions comprising one or more of these compounds. Also provided are methods of reducing LDL cholesterol level in a subject in need thereof that include administering to the subject one or more of the cyclic polypeptide compounds or a pharmaceutical composition provided herein.

Cyclic polypeptides for PCSK9 inhibition

The synthesis of various pyrazino[1',2&#x2032;:1,5]pyrrolo[2,3-B]-indole-1,4-dione analogs has been successfully implemented in the present application. From these efforts, compounds having the structure of Formula I-a or Formula I-b: or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, are provided herein. These biologically active derivatives have been used to effectively treat various diseases including cancer.

Substituted pyrazino[1',2&#x2032;:1,5]pyrrolo[2,3-b]indole-1,4-diones for cancer treatment

The present invention provides inhibitors and/or antagonists of plasma kallikrein. Also provided are methods of utilizing the inhibitors as therapeutics.

Peptide and peptidomimetic inhibitors

The synthesis of various pyrazino[1',2&#x2032;:1,5]pyrrolo[2,3-b]-indole-1,4-dione analogs has been successfully implemented in the present application. From these efforts, compounds having the structure of Formula I-c: or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein R, R, R-R, R, R, and n are as defined herein, are provided. These biologically active derivatives have been further used to prepare cell-specific drug conjugates effective in treating various diseases including cancer.

Substituted pyrazino[1',2&#x2032;:1 ,5]pyrrolo[2,3-b]indole-1,4-diones for cancer treatment

The present application provides, among other things, a compound of Formula I-a and/or I-b, or a pharmaceutically acceptable salt thereof, wherein the variables are defined in the specification. The compounds of the invention are useful for treating various diseases including cancer.

Substituted pyrazino[1',2&#x2032;:1 ,5]pyrrolo[2,3-b]-indole-1,4-diones for cancer treatment

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Cambridge, MA, United States of America

Nicolas Cedric Boyer