Ariad Pharmaceuticals, Inc.

Aileron Therapeutics, Inc.

Merck Sharp + Dohme Corp.

Agency for Science, Technology and Research

Msd International Gmbh (singapore Branch)

Tomi K Sawyer

William C Shakespeare

Yihan Wang

Rajeswari Sundaramoorthi

Chester A Metcalf, Iii

David C Dalgarno

Regine Bohacek

Huw M Nash

Xiaotian Zhu

Wei-Sheng Huang

R Mathew Thomas

Dong Zou

Jiwei Qi

Jan Antoinette C Romero

Noriyuki Kawahata

David Allen Annis

Rosana Kapeller-Libermann

Vincent Guerlavais

Bradford Graves

Eric Feyfant

Carl Elkin

Michael G Yang

Manfred Weigele

Ravi P Nargund

Anandan Palani

Elisabetta Bianchi

Antonello Pessi

Qiaolin Deng

Federica Orvieto

Paul E Carrington

Charles Joseph Eyermann

Jan Antoinette Romero

Chester A Metcalf

Terence P Keenan

Nicolas Cedric Boyer

Sookhee Nicole Ha

Chunhui Huang

Chandra Shekhar Verma

Charles William Johannes

Rosanna Kapeller-Libermann

Jiawen Han

Tsz Ying Yuen

Jia-Wen Han

John D Iuliucci

Rosana Kapeller-Llbermann

Justin Noehre

Jan Antionette C Romero

George P Luke

Craig S Takeuchi

Noriyuki H Kawahata

Karina Macek

Virginia A Jacobsen

Michael B Garrigou

Pietro Aronica

Srinivasaraghavan Kannan

Anthony W Partridge

Bradford J Graves

Chester A Iii Metcalf

Mathew R Thomas

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

Long-acting co-agonists of the glucagon and GLP-1 receptors are described.

Long-acting co-agonists of the glucagon and GLP-1 receptors

Provided herein are peptidomimetic macrocycles containing amino acid sequences with at least two modified amino acids that form an intramolecular cross-link that can help to stabilize a secondary structure of the amino acid sequence. Suitable sequences for stabilization include those with homology to the p53 protein. These sequences can bind to the MDM2 and/or MDMX proteins. Also provided herein are methods of using such macrocycles for the treatment of diseases and disorders, such as cancers or other disorders characterized by a low level or low activity of a p53 protein or high level of activity of a MDM2 and/or MDMX protein.

Peptidomimetic macrocycles

Disclosed are peptidomimetic macrocycles comprising a helix, such as an alpha helix, and methods of using such macrocycles for the treatment of disease such as cancer. In other aspects, the peptidomimetic macrocycle comprises an &#x3b1;,&#x3b1;-disubstituted amino acid, or may comprise a crosslinker linking the &#x3b1;-positions of at least two amino acids or at least one of said two amino acids may be an &#x3b1;,&#x3b1;-disubstituted amino acid. Further included is the targeting of components of the Wnt signaling pathway such as the Tcf4-/3-catenin complex.

The present invention provides biologically active peptidomimetic macrocycles with improved properties relative to their corresponding polypeptides. The invention additionally provides methods of preparing and using such macrocycles, for example in therapeutic applications.

Peptidomimetic macrocycles with improved properties

This invention relates to compounds of the general formula: 

Substituted acetylenic pyrazolo[1,5-a]pyrimidines as kinase inhibitors

Biologically active crosslinked polypeptides with improved properties relative to their corresponding precursor polypeptides, having good cell penetration properties and reduced binding to human proteins; and methods of identifying and making such improved polypeptides.

Acetylenic heteroaryl compounds

Substituted acetylenic imidazo[1,2-A]pyridazines as kinase inhibitors

The present invention provides biologically active peptidomimetic macrocycles for the treatment of cell proliferative disorders such as cancer and immunoproliferative disease.

Therapeutic peptidomimetic macrocycles

Substituted acetylenic imidazo[1,2-A]pyrazine compounds as kinase inhibitors

Growing community of inventors

Southborough, MA, United States of America

Tomi K Sawyer