remibrutinib   Click here for help

GtoPdb Ligand ID: 10457

Synonyms: compound 25 [PMID: 32083858] | example 6 [WO2015079417A1] | LOU-064 | LOU064 | LOU064-NXA | NVP-LOU064-NXA
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Remibrutinib (LOU064) is one of the examples claimed in Novartis' patent WO2015079417A1 [2], for novel amino pyrimidine derivatives that act as Bruton's tyrosine kinase (BTK) inhibitors and which claims their potential to treat autoimmune disorders, inflammatory/allergic diseases, transplant rejection and cancers of hematopoietic origin or solid tumours. The formal chemical name (LOU064; remibrutinib) to structure disclosure was published in February 2020 [1]. LOU064 is a covalent BTK inhibitor that binds the inactive conformation of the enzyme. This improves its selectivity compared to currently marketed covalent BTK inhibitors, and renders it more suitable for use in non-oncology indications.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 7
Hydrogen bond donors 2
Rotatable bonds 11
Topological polar surface area 110.44
Molecular weight 507.21
XLogP 4.1
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES C=CC(=O)N(CCOc1c(N)ncnc1c1cc(F)cc(c1C)NC(=O)c1ccc(cc1F)C1CC1)C
Isomeric SMILES C=CC(=O)N(CCOc1c(N)ncnc1c1cc(F)cc(c1C)NC(=O)c1ccc(cc1F)C1CC1)C
InChI InChI=1S/C27H27F2N5O3/c1-4-23(35)34(3)9-10-37-25-24(31-14-32-26(25)30)20-12-18(28)13-22(15(20)2)33-27(36)19-8-7-17(11-21(19)29)16-5-6-16/h4,7-8,11-14,16H,1,5-6,9-10H2,2-3H3,(H,33,36)(H2,30,31,32)
InChI Key CUABMPOJOBCXJI-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
Remibrutinib (LOU064) is being evaluated as a treatment for a range of inflammatory conditions; maximum Phase 2 as of February 2020. In September 2021, Novartis announced (by press release) positive outcomes from their Phase 2b study of remibrutinib in patients with chronic spontaneous urticaria (CSU; NCT03926611) [5]. Remibrutinib was reported to achieve rapid and effective disease control in patients with CSU that was previously inadequately controlled by histamine H1 antagonists (antihistamines), with a favourable safety profile and good tolerability.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04109313 Open-label, Multicenter, Extension Study to Evaluate Long-term Safety and Tolerability of LOU064 in Subjects With CSU Phase 2 Interventional Novartis
NCT03944707 Study of Efficacy and Safety of LOU064 in Inadequately Controlled Asthma Patients Phase 2 Interventional Novartis
NCT04035668 A Phase 2 Study to Evaluate the Safety and Efficacy of LOU064 in Patients With Moderate to Severe Sjögren's Syndrome Phase 2 Interventional Novartis
NCT03926611 Dose-finding Study to Evaluate Efficacy and Safety of LOU064 in Patients With CSU Inadequately Controlled by H1-antihistamines Phase 2 Interventional Novartis
NCT03918980 Single Dose and Multiple Dose Study to Assess Safety and Tolerability of LOU064 Phase 1 Interventional Novartis 4
Pharmacokinetics Click here for help
Elimination
Remibrutinib appears to be eliminated predominantly via the CYP3A4 pathway [3].