ozanimod   Click here for help

GtoPdb Ligand ID: 8709

Synonyms: RPC-1063 | RPC1063 | Zeposia®
Approved drug PDB Ligand Immunopharmacology Ligand
ozanimod is an approved drug (EMA & FDA (2020))
Compound class: Synthetic organic
Comment: Ozanimod (RPC1063) is a novel, orally available, specific and potent agonist of the sphingosine 1-phosphate 1 receptor (S1P1R) and SIP5Rs [8]. Ozanimod is compound 86 in patent US20110172202 A1 [7], which specifies the (S)-enantiomer.
Ozanimod reduces chronic inflammation and alleviates kidney pathology in a mouse model of systemic lupus erythematosus (SLE), which suggests that ozanimod may offer clinical benefit as a SLE therapeutic [10].
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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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 4
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 104.2
Molecular weight 404.18
XLogP 3.73
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES OCCNC1CCc2c1cccc2c1noc(n1)c1ccc(c(c1)C#N)OC(C)C
Isomeric SMILES OCCN[C@H]1CCc2c1cccc2c1noc(n1)c1ccc(c(c1)C#N)OC(C)C
InChI InChI=1S/C23H24N4O3/c1-14(2)29-21-9-6-15(12-16(21)13-24)23-26-22(27-30-23)19-5-3-4-18-17(19)7-8-20(18)25-10-11-28/h3-6,9,12,14,20,25,28H,7-8,10-11H2,1-2H3/t20-/m0/s1
InChI Key XRVDGNKRPOAQTN-FQEVSTJZSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Argollo M, Furfaro F, Gilardi D, Roda G, Allocca M, Peyrin-Biroulet L, Danese S. (2020)
Modulation of sphingosine-1-phosphate in ulcerative colitis.
Expert Opin Biol Ther, 20 (4): 413-420. [PMID:32093531]
2. Celgene. 
New Analyses from Pivotal Phase III Trials of Oral Ozanimod in Relapsing Multiple Sclerosis To Be Presented at the 2018 American Academy of Neurology Annual Meeting.
Accessed on 26/04/2018. Modified on 26/04/2018. celgene.com, http://ir.celgene.com/releasedetail.cfm?ReleaseID=1064723
3. Cohen JA, Comi G, Selmaj KW, Bar-Or A, Arnold DL, Steinman L, Hartung HP, Montalban X, Kubala Havrdová E, Cree BAC et al.. (2019)
Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): a multicentre, randomised, 24-month, phase 3 trial.
Lancet Neurol, 18 (11): 1021-1033. [PMID:31492652]
4. Comi G, Kappos L, Selmaj KW, Bar-Or A, Arnold DL, Steinman L, Hartung HP, Montalban X, Kubala Havrdová E, Cree BAC et al.. (2019)
Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial.
Lancet Neurol, 18 (11): 1009-1020. [PMID:31492651]
5. Derfuss T, Mehling M, Papadopoulou A, Bar-Or A, Cohen JA, Kappos L. (2020)
Advances in oral immunomodulating therapies in relapsing multiple sclerosis.
Lancet Neurol, 19 (4): 336-347. [PMID:32059809]
6. Gonzalez-Cabrera PJ, Jo E, Sanna MG, Brown S, Leaf N, Marsolais D, Schaeffer MT, Chapman J, Cameron M, Guerrero M et al.. (2008)
Full pharmacological efficacy of a novel S1P1 agonist that does not require S1P-like headgroup interactions.
Mol Pharmacol, 74 (5): 1308-18. [PMID:18708635]
7. Martinborough E, Boehm MF, Yeager AR, Tamiya J, Huang L, Brahmachary E, Moorjani M, Timony GA, Brooks JL, Peach R et al.. (2011)
Selective sphingosine 1 phosphate receptor modulators and methods of chiral synthesis.
Patent number: US20110172202 A1. Assignee: Martinborough E, Boehm MF, Yeager AR, Tamiya J, Huang L, Brahmachary E, Moorjani M, Timony GA, Brooks JL, Peach R et al.. Priority date: 13/11/2009. Publication date: 14/07/2011.
8. Scott FL, Clemons B, Brooks J, Brahmachary E, Powell R, Dedman H, Desale HG, Timony GA, Martinborough E, Rosen H et al.. (2016)
Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1 ) and receptor-5 (S1P5 ) agonist with autoimmune disease-modifying activity.
Br J Pharmacol, 173 (11): 1778-92. [PMID:26990079]
9. Shimano K, Maeda Y, Kataoka H, Murase M, Mochizuki S, Utsumi H, Oshita K, Sugahara K. (2019)
Amiselimod (MT-1303), a novel sphingosine 1-phosphate receptor-1 functional antagonist, inhibits progress of chronic colitis induced by transfer of CD4+CD45RBhigh T cells.
PLoS One, 14 (12): e0226154. [PMID:31805144]
10. Taylor Meadows KR, Steinberg MW, Clemons B, Stokes ME, Opiteck GJ, Peach R, Scott FL. (2018)
Ozanimod (RPC1063), a selective S1PR1 and S1PR5 modulator, reduces chronic inflammation and alleviates kidney pathology in murine systemic lupus erythematosus.
PLoS ONE, 13 (4): e0193236. [PMID:29608575]