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Synonyms: GSK-1223249 | GSK1223249
Compound class:
Antibody
Comment: Ozanezumab is a humanised mouse monoclonal antibody targeting NOGO-A (reticulon-4, RTN4). This antibody is in GlaxoSmithKline's development pipeline of drugs for rare diseases, in this case amyotrophic lateral sclerosis (ALS aka motor neurone disease or MND) and was also investigated for multiple sclerosis (MS).
Although peptide sequences for ozanezumab are available, a BLAST search provided no exact matches with patented protein sequences 
Ligand Activity Visualisation ChartsThese 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. ✖ |
| No information available. |
Summary of Clinical Use  |
| Ozanezumab has reached Phase 2 clinical trial for ALS (see NCT01753076). Two Phase 1 trials of ozanezumab in MS have been terminated. |
| Mechanism Of Action and Pharmacodynamic Effects |
| NOGO-A is expressed in higher levels in the central nervous system of ALS patients, where the protein appears to inhibit neurite outgrowth. This inhibitory effect reduces the capacity of neurons to form junctions with muscles, promoting denervation which leads to muscle weakness [4]. Inhibiting this action of NOGO-A is predicted to abrogate the loss of connections between motor neurones and muscles. The role of aberrant axon guidance in ALS is reviewed in [5].. Studies using murine monoclonal IN-1 [2] helped to confirm that anti-NOGO-A antibodies have neurite outgrowth potentiating activity [1,6], and that NOGO-A represents a viable and druggable target. Patent US8362208 covers GlaxoSmithKline's development of anti-NOGO-A antibodies [3], with clone H28L16 being a likely candidate for ozanezumab. |
| Clinical Trials | |||||
| Clinical Trial ID | Title | Type | Source | Comment | References |
| NCT01753076 | Study of Ozanezumab (GSK1223249) Versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis | Phase 2 Interventional | GlaxoSmithKline | ||
