Cubist Pharmaceuticals, Incorporated

C4 Therapeutics, Inc.

Cubist Pharmacueticals, Inc.

Paq Therapeutics Inc.

Merck Sharp + Dohme Corp.

Ning Yin

Yu Gui Gu

Yong He

Chester A Metcalf, Iii

Dylan C Alexander

Jason B Cross

Christopher G Nasveschuk

Gesine Kerstin Veits

Katrina L Jackson

Rhamy Zeid

Moses Moustakim

Jeremy L Yap

Robert Busch

Roland Ellwood Dolle

Jon Christian Baber

Dongpeng Wan

Nan Ji

Yanke Liang

Kiel Lazarski

Hui Qiu

Dong Zou

Alexander W Hird

Andre Lee Pearson

Hongwei Huang

Scott Joseph Eron

Andrew Charles Good

Chester A Iii Metcalf

This invention provides Degron compounds which bind to cereblon which is a component of the E3 ubiquitin ligase. The Degrons provided herein can be used to modulate the activity of cereblon either alone or as covalently linked to a Tail. Alternatively, the Degron can be linked to a Targeting Ligand which binds to a Target Protein for protein degradation.

Bicyclic-substituted glutarimide cereblon binders

Provided herein are KRAS G12D proteolysis targeting chimeras (PROTACs), compositions comprising the KRAS G12D PROTACs, and methods of making and using the KRAS G12D PROTACs, e.g., to promote degradation of KRAS G12D and/or treat KRAS G12D-associated cancers. In an embodiment, the KRAS G12D PROTAC has the following structural formula:[KRAS G12Di]-L'-[Degron],or a pharmaceutically acceptable salt thereof, wherein values for the variables (e.g., KRAS G12Di, L′, Degron) are as described herein.

KRAS G12D proteolysis targeting chimeras

BRD9 protein degradation compounds or pharmaceutically acceptable salts thereof are provided for the treatment of disorders mediated by BRD9, including but not limited to abnormal cellular proliferation.

Compounds for targeted degradation of BRD9

A BRD9 protein degrading compound of structure or a pharmaceutically acceptable salt thereof is provided for the treatment of a disorder mediated by BRD9, including but not limited to abnormal cellular proliferation including cancer.

Aryl substituted diazabicyclooctanes (DBO) compounds that inhibit &#x3b2;-lactamases of class A, class C or class D and potentiate &#x3b2;-lactam antibiotics are disclosed. In particular, this disclosure provides DBO compounds that, when used in the disclosed Synergy MIC Assay with a &#x3b2;-lactam antibiotic at a fixed concentration have an MIC of 8 &#x3bc;g/mL or less against one or more isogenic &#x3b2;-lactamase expressing bacterial strains.

Beta-lactamase inhibitors

&#x3b2;-Lactamase inhibitor compounds (BLIs) are disclosed, including compounds that have activity against class A, class C or class D &#x3b2;-lactamases. Methods of manufacturing the BLIs, and uses of the compounds in the preparation of pharmaceutical compositions and antibacterial applications are also disclosed.

1,3,4-oxadiazole and 1,3,4-thiadiazole &#x3b2;-lactamase inhibitors

1,3,4-oxadiazole and 1,3,4-thiadiazole beta-lactamase inhibitors

Isoxazole beta-lactamase inhibitors

1,2,4-oxadiazole and 1,2,4-thiadiazole &#x3b2;-lactamase inhibitors

The cephalosporin compound of formula (I) is disclosed, which exhibits antibiotic activity against Gram-negative (e.g.,) and Gram-positive (e.g., methicillin-resistant) bacteria. Methods of manufacturing the compound of formula (I), and uses of the compound in the preparation of pharmaceutical compositions and antibacterial applications are also disclosed.

Cephalosporin compound

Growing community of inventors

Lexington, MA, United States of America

Ning Yin