D.e. Shaw Research, LLC

Relay Therapeutics, Inc.

Paul Maragakis

Alexander M Taylor

Fabrizio Giordanetto

Jack Benjamin Greisman

W Patrick Walters

Mark Andrew Murcko

Lucian V DiPietro

André Lescarbeau

Sathesh P Bhat

Elizabeth Helen Kelley

Eric Therrien

Markus Kristofer Dahlgren

Kelley C Shortsleeves

Levi Charles Thomas Pierce

Brian K Albrecht

John K Salmon

Yong Tang

Peter Skopp

Hunter Nisonoff

Heike Schoenherr

Markus Kristofer Dahlgeren

Discovering molecules (which may be known or may never have been cataloged or ever synthesized) that have desired characteristics is addressed using a machine learning approach. As compared to a brute-force search of a database of known molecules, which may not be computationally feasible, the present machine learning approach renders identification of both known and unknown molecules computationally tractable. Furthermore, the computational effort is largely shifted to training of the machine learning system using a database of known molecules, and the generation of molecules to match any particular characteristics requires relatively little computation. The molecules using the present approach may be further studied, for example, with computer-based simulation or after physical synthesis using biological experimentation to ultimately yield useful chemical compounds.

Molecular graph generation from structural features using an artificial neural network

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure.

Pyrazolo[3,4-b]pyrazine SHP2 phosphatase inhibitors and methods of use thereof

The present invention relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the invention. The present invention further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds ad compositions of the invention.

SHP2 phosphatase inhibitors and methods of use thereof

The present disclosure relates to compounds of formula (I) and pharmaceutical compositions thereof and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure. 

Substituted pyrazolo[3,4-b]pyrazines as SHP2 phosphatase inhibitors

The present invention relates to novel compounds having the general formula: and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the invention. The present invention further relates to, but is not limited to, methods for suppressing tumor cell growth, ameliorating the pathogenesis of systemic lupus erythematosus, and the treatment of various other disorders, including Noonan syndrome, diabetes, neutropenia, neuroblastoma, melanoma, juvenile leukemia, juvenile myelomonocytic leukemia, chronic myelomonocytic leukemia, acute myeloid leukemia, and other cancers associated with SHP2 deregulation with the compounds and compositions of the invention, alone or in combination with other treatments. Other cancers associated with SHP2 deregulation include HER2-positive breast cancer, triple-negative breast cancer, ductal carcinoma of the breast, invasive ductal carcinoma of the breast, non-small cell lung cancer, esophageal cancer, gastric cancer, squamous-cell carcinoma of the head and neck (SCCHN), and colon cancer.

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New York, NY, United States of America

Paul Maragakis