crizanlizumab   Click here for help

GtoPdb Ligand ID: 10550

Synonyms: Adakveo® | crizanlizumab-tmca | hSel001 [2] | SEG101
Approved drug
crizanlizumab is an approved drug (FDA (2019), EMA (2020))
Compound class: Antibody
Comment: Crizanlizumab is a humanized anti-P-selectin monoclonal that was developed by Selexys Pharmaceuticals (and later acquired by Novartis) as a preventative therapy for sickle cell crises [1]. The antibody and its use are claimed in Selexys' patent WO2012088265A1 [2]. Crizanlizumab was designed to limit complement activation. In clinical trial no anti-crizanlizumab antibodies could be detected [1].
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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
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Summary of Clinical Use Click here for help
The US FDA granted crizanlizumab accelerated approval to reduce the frequency of vaso-occlusive crises in sickle cell disease patients in November 2019. This is the first targeted therapy to be made available for this disease.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Crizanlizumab binds to P-selectin on activated endothelial cells and blocks its interaction with P-selectin glycoprotein ligand 1 (PSGL-1) [2]. This mechanism helps to ameliorate the abnormal adhesion of sickled erythrocytes to endothelial cells that underlies vascular occlusion and pain crises in sickle cell disease. Crizanlizumab is able to dissociate preformed P-selectin/PSGL-1 complexes.