The Scripps Research Institute

Abide Therapeutics, Inc.

Vividion Therapeutics, Inc.

H. Lundbeck A/s

Lundbeck La Jolla Research Center, Inc.

Leiden University

Benjamin F Cravatt

Micah J Niphakis

Todd Kevin Jones

Cheryl A Grice

Jae Won Chang

Kenneth M Lum

Justin S Cisar

Matthew Patricelli

Armand Cognetta

Norton B Gilula

Richard A Lerner

David S Weinstein

Benjamin Horning

Ekaterina Vinogradova

Bruno Correia

Jonathan J Hulce

Dean Stamos

Gabe Simon

Dale L Boger

Alan Saghatelian

Daniel K Nomura

Richrd A Lerner

Keriann M Backus

Daisuke Ogasawara

Kyle P Chiang

Kim D Janda

Olivia Delene Weber

Erik J Sorensen

Megan Blewett

Katsunori Tsuboi

Xiaoyu Zhang

Chu Wang

Dong-Hui Wang

Bruno E Correia

John R Teijaro

Alexander Adibekian

Ku-Lung Hsu

Sherry Niessen

Brian Nordin

Jonathan Z Long

Kristen Baltgalvis

Weiwei Li

Todd Kinsella

Nadim Jessani

Arul Joseph

Martha Lovato

Gregory Adam

Christopher G Parker

Vincent Crowley

Jon A Ashley

Jonathan Hulce

Taka-Aki Ichu

Andreu Viader

Hui Deng

Tom Van Der Wel

Marcelis Van Der Stelt

Keriann Backus

This disclosure provides compounds and compositions which may be modulators of MAGL and/or ABHD6 and their use as medicinal agents, processes for their preparation, and pharmaceutical compositions that include disclosed compounds as at least one active agent. The disclosure also provides for method of treating a patient in need thereof, where the patient is suffering from post-traumatic stress disorder comprising administering a disclosed compound or composition.

Carbamate compounds and methods of making and using same

Provided herein are compounds and compositions useful as modulators of ABHD12. Furthermore, the subject compounds and compositions are useful as immunotherapies in treating, for instance, cancer or infectious diseases.

ABHD12 inhibitors and methods of making and using same

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 methods and compounds for inducing DDB1- and CUL4-associated factor 16 (DCAF16)-mediated protein degradation in mammalian cells. In some embodiments, also disclosed herein are methods of modulating the substrate selectivity of a DCAF16-CUL4-RBX1-DDB1 complex (CRL4) for modulating protein degradation.

Compounds and methods for DCAF-mediated protein degradation

Disclosed herein are methods for identifying proteins as targets for interaction with a small molecule ligand. Also disclosed herein are small molecule ligands and compositions for use in profiling druggable proteins.

Photoreactive ligands and uses thereof

This disclosure provides compounds and compositions which may be modulators of MAGL and/or ABHD6 and their use as medicinal agents, processes for their preparation, and pharmaceutical compositions that include disclosed compounds as at least one active agent. The disclosure also provides for a method of treating a patient in need thereof, where the patient is suffering from post-traumatic stress disorder comprising administering a disclosed compound or composition.

Disclosed herein are methods, compositions, probes, assays and kits for identifying a lipid binding protein as a drug binding target. Also disclosed herein are methods, compositions, and probes for mapping a ligand binding site on a lipid binding protein, identification of lipid binding proteins, generating drug-lipid binding protein profiles, high throughput drug screening, and identification of drugs as potential lipid binding protein ligands.

Lipid probes and uses thereof

Cells produce electrophilic products with the potential to modify and affect the function of proteins. Chemoproteomic methods have provided a means to qualitatively inventory proteins targeted by endogenous electrophiles; however, ascertaining the potency and specificity of these reactions to identify the most sensitive sites in the proteome to electrophilic modification requires more quantitative methods. Here, we describe a competitive activity-based profiling method for quantifying the reactivity of electrophilic compounds against 1000+ cysteines in parallel in the human proteome. Using this approach, we identify a select set of proteins that constitute hot spots for modification by various lipid-derived electrophiles, including the oxidative stress product 4-hydroxnonenal (HNE). We show that one of these proteins, ZAK kinase, is labeled by HNE on a conserved, active site-proximal cysteine, resulting in enzyme inhibition to create a negative feedback mechanism that can suppress the activation of JNK pathways by oxidative stress.

Cysteine-reactive ligand discovery in proteomes

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

Disclosed herein are methods, compositions, probes, polypeptides, assays, and kits for identifying a cysteine containing protein as a binding target for a small molecule fragment. Also disclosed herein are methods, compositions, and probes for mapping a biologically active cysteine site on a protein and screening a small molecule fragment for interaction with a cysteine containing protein.

Cysteine reactive probes and uses thereof

Provided herein are triazole compounds and pharmaceutical compositions comprising said compounds useful as modulators of DAGL(&#x3b1;) and DAGL(&#x3b2;). In some embodiments, the compounds described herein are selective DAGL(&#x3b1;) inhibitors. Furthermore, the subject compounds and compositions are useful for the treatment of neurodegenerative or neuroinflammatory disease.

Triazole DAGL&#x3b1; inhibitors

Provided herein are N-hydroxy bicyclic hydantoin carbamates and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of serine hydrolases. Furthermore, the subject compounds and compositions are useful for the treatment of one or more of cancer, pain, diabetes, obesity/metabolic syndrome, epilepsy, traumatic brain injury, and inflammation.

N-hydroxy bicyclic hydantoin carbamates as tools for identification of serine hydrolase targets

Growing community of inventors

La Jolla, CA, United States of America

Benjamin F Cravatt