RGD Reference Report - Discovery of LOU064 (Remibrutinib), a Potent and Highly Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. - Rat Genome Database

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Discovery of LOU064 (Remibrutinib), a Potent and Highly Selective Covalent Inhibitor of Bruton's Tyrosine Kinase.

Authors: Angst, Daniela  Gessier, François  Janser, Philipp  Vulpetti, Anna  Wälchli, Rudolf  Beerli, Christian  Littlewood-Evans, Amanda  Dawson, Janet  Nuesslein-Hildesheim, Barbara  Wieczorek, Grazyna  Gutmann, Sascha  Scheufler, Clemens  Hinniger, Alexandra  Zimmerlin, Alfred  Funhoff, Enrico G  Pulz, Robert  Cenni, Bruno 
Citation: Angst D, etal., J Med Chem. 2020 May 28;63(10):5102-5118. doi: 10.1021/acs.jmedchem.9b01916. Epub 2020 Mar 4.
RGD ID: 151665122
Pubmed: PMID:32083858   (View Abstract at PubMed)
DOI: DOI:10.1021/acs.jmedchem.9b01916   (Journal Full-text)

Bruton's tyrosine kinase (BTK), a cytoplasmic tyrosine kinase, plays a central role in immunity and is considered an attractive target for treating autoimmune diseases. The use of currently marketed covalent BTK inhibitors is limited to oncology indications based on their suboptimal kinase selectivity. We describe the discovery and preclinical profile of LOU064 (remibrutinib, 25), a potent, highly selective covalent BTK inhibitor. LOU064 exhibits an exquisite kinase selectivity due to binding to an inactive conformation of BTK and has the potential for a best-in-class covalent BTK inhibitor for the treatment of autoimmune diseases. It demonstrates potent in vivo target occupancy with an EC90 of 1.6 mg/kg and dose-dependent efficacy in rat collagen-induced arthritis. LOU064 is currently being tested in phase 2 clinical studies for chronic spontaneous urticaria and Sjoegren's syndrome.



Disease Annotations    

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Btk  (Bruton tyrosine kinase)

Genes (Mus musculus)
Btk  (Bruton agammaglobulinemia tyrosine kinase)

Genes (Homo sapiens)
BTK  (Bruton tyrosine kinase)


Additional Information