DYRK/CLK PROTACS AND USES THEREOF
Abstract
The present invention relates to bifunctional compounds, which find utility to degrade and (inhibit) one or more of the following kinases: DYRK1A, DYRK1B, DYRK2, DYRK3, CLK1, CLK2, CLK3, CLK4, and HASPIN. In particular, the present invention is directed to compounds, which contain on one end an E3 ubiquitin ligase binding moiety which binds to an E3 ubiquitin ligase and on the other end a moiety which binds one or more of the following kinases: DYRK1A, DYRK1B, DYRK2, DYRK3, CLK1, CLK2, CLK3, CLK4, and HASPIN, such that the one or more kinases is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of the one or more kinases. The bifunctional compounds serve as therapeutics for the treatment of Alzheimer's disease, down syndrome, diabetes, an autoimmune disease, an inflammatory disorder (e.g., airway inflammation, osteoarthritis (e.g., knee related osteoarthritis)), cancer (e.g., glioblastoma, prostate cancer, metastatic breast cancer, metastatic lung cancer, multiple myeloma, secondary metastatic tumors of the brain, colorectal cancer), a viral infection (e.g., SARS-CoV-2 infection (e.g., COVID-19)), and other diseases.
Inventors 4
- Hulme, Christopher
- Schofield, Kevin
- Walter B. Becker Aachen author as filed: Becker, Walter
- Gerrit Wilms Aachen author as filed: Wilms, Gerrit Franz
Inventors are linked to an Aachen author when surname and first name match exactly one author.
Applicants
- ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIVERSITY OF ARIZONA
- RWTH AACHEN, MEDICAL FACULTY RWTH Aachen University
- Univ Arizona
Cited papers 0 in the database
Non-patent literature as cited (2)
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- - CHAN KWOK-HO, ZENGERLE MICHAEL, TESTA ANDREA, CIULLI ALESSIO: "Impact of Target Warhead and Linkage Vector on Inducing Protein Degradation: Comparison of Bromodomain and Extra-Terminal (BET) Degraders Derived from Triazolodiazepine (JQ1) and Tetrahydroquinoline (I-BET726) BET Inhibitor Scaffolds", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 61, no. 2, 25 January 2018 (2018-01-25), US , pages 504 - 513, XP055930443, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.6b01912