The Scripps Research Institute

Vividion Therapeutics, Inc.

Araxes Pharma LLC

Activx Biosciences, Inc.

Matthew Patricelli

Benjamin F Cravatt

David S Weinstein

Benjamin Horning

Dean Stamos

Ekaterina Vinogradova

Gabe Simon

Yi Liu

Pingda Ren

Liansheng Li

Erik J Sorensen

Gregory Adam

Brian Nordin

Martha Lovato

Kristen Baltgalvis

Todd Kinsella

Matthew Robert Janes

Ulf Peters

Disclosed herein are compositions and methods for modulating cereblon neosubstrates. A small molecule modulator of Formula (I*), or a pharmaceutically acceptable salt or solvate thereof can be used to modulate cereblon neosubstrates.

Cereblon modulators and uses thereof

Disclosed herein are in vivo engineered cereblon protein and methods of making the same. The in vivo engineered cereblon protein can include a site-specific non-naturally occurring modification at cysteine 287 as set forth in SEQ ID NO:1, or cysteine 286 as set forth in SEQ ID NO:2 or 3, the modification comprising a moiety resulting from an in vivo Michael addition reaction between an exogenous Michael acceptor and the cysteine 287 as set forth in SEQ ID NO:1, or cysteine 286 as set forth in SEQ ID NO:2 or 3.

In vivo engineered cereblon protein

Combination therapies for treatment of cancers associated with mutations in the KRAS gene are provided. Compositions comprising therapeutic agents for treatment of cancers associated with mutations in the KRAS gene are also provided.

Combination therapies for treatment of cancer

Provided herein are compositions, reactions mixtures, mutant Ras proteins, kits, substrates, and systems for selecting a Ras antagonist, as well as methods of using the same.

Method for screening inhibitors of Ras

Methods and compositions are described for analyzing complex protein mixtures, such as proteomes, using activity-based probes. In particular, probes that specifically react with and bind to the active form of one or more target proteins are employed. Labeled peptides obtained from the labeled active target proteins can be used in screening and identification procedures, and can be related to the identity, presence, amount, or activity of active members of the desired target protein class. The methods and compositions described herein can be used, for example, to provide diagnostic information concerning pathogenic states, in identifying proteins that may act as therapeutic targets, and in drug discovery.

Protein profiling platform

Methods and compositions are described for analyzing complex protein mixtures using fluorescent activity-based probes. In particular, probes that specifically react with and bind to the active form of one or more target proteins are employed. Fluorescent signals obtained from the labeled active target proteins can be related to the presence or amount of active members of the desired target protein class. The methods and compositions described herein can be used, for example, to provide diagnostic information concerning pathogenic states, in identifying proteins that may act as therapeutic targets, and in drug discovery.

Activity based probe analysis

The present invention provides methods for analyzing proteomes, as cells or lysates. The analysis is based on the use of probes that have specificity to the active form of proteins, particularly enzymes and receptors. The probes can be identified in different ways. In accordance with the present invention, a method is provided for generating and screening compound libraries that are used for the identification of lead molecules, and for the parallel identification of their biological targets. By appending specific functionalities and/or groups to one or more binding moieties, the reactive functionalities gain binding affinity and specificity for particular proteins and classes of proteins. Such libraries of candidate compounds, referred to herein as activity-based probes, or ABPs, are used to screen for one or more desired biological activities or target proteins.

Proteomic analysis

Growing community of inventors

San Diego, CA, United States of America

Matthew Patricelli