Ozanimod | RPC1063 | CAS#1306760-87-1 | Immunomodulator

MedKoo Cat#: 206177 | Name: Ozanimod

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Ozanimod, also known as RPC1063, is a selective sphingosine 1 phosphate receptor modulators and methods which may be useful in the treatment of S1P1-associated diseases. Ozanimod has demonstrated efficacy in treating various diseases such as depression, fibromyalgia and obesity.

Chemical Structure

Ozanimod

CAS#1306760-87-1 (free base)

Theoretical Analysis

MedKoo Cat#: 206177

Name: Ozanimod

CAS#: 1306760-87-1 (free base)

Chemical Formula: C23H24N4O3

Exact Mass: 404.1848

Molecular Weight: 404.46

Elemental Analysis: C, 68.30; H, 5.98; N, 13.85; O, 11.87

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 3,750.00	Ready to ship
2g	USD 6,250.00	Ready to ship

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Related CAS #

1306760-87-1 (free base) 1618636-37-5 (HCl)

Synonym

RPC1063; RPC-1063; RPC 1063; Ozanimod

IUPAC/Chemical Name

(S)-5-(3-(1-((2-hydroxyethyl)amino)-2,3-dihydro-1H-inden-4-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile

InChi Key

XRVDGNKRPOAQTN-FQEVSTJZSA-N

InChi Code

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

SMILES Code

N#CC1=CC(C2=NC(C3=CC=CC4=C3CC[C@@H]4NCCO)=NO2)=CC=C1OC(C)C

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>5 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C9R04B19

QC Data

View QC data: current batch, Lot#C9R04B19

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Ozanimod (RPC-1063) is a potent and selective S1P1 and S1P5 receptor agonist with EC50s of 410 pM and 11 nM in [35S]-GTPγS binding, respectively

In vitro activity:

It was hypothesized that ozanimod, a selective S1PR type 1 ligand, will attenuate VSM synthetic phenotypic expression and autophagic flux in primary human brain VSM cells following acute hypoxia plus glucose deprivation (HGD; in vitro ischemic-like injury) exposure. Cells were treated with ozanimod and exposed to normoxia or HGD. Crystal violet staining, standard immunoblotting, and immunocytochemical labeling techniques assessed cellular morphology, vacuolization, phenotype, and autophagic state. It was observed that HGD temporally decreased VSM cell viability and concomitantly increased vacuolization, both of which ozanimod reversed. HGD induced a simultaneous elevation and reduction in levels of pro- and anti-autophagic proteins respectfully, and ozanimod attenuated this response. Protein levels of VSM phenotypic biomarkers, smoothelin and SM22, were decreased following HGD. Furthermore, it was observed that an HGD-induced epithelioid and synthetic morphological appearance accompanied by disorganized cytoskeletal filaments which was rescued by ozanimod. Thus, it is concluded that ozanimod, a selective S1PR1 ligand, protects against acute HGD-induced phenotypic switching and promotes cell survival, in part, by attenuating HGDinduced autophagic flux thus improving vascular patency in response to acute ischemia-like injury. Am J Physiol Cell Physiol. 2021 Mar 31. https://pubmed.ncbi.nlm.nih.gov/33788630/

In vivo activity:

The purpose of this study was to assess RPC1063 for its therapeutic utility in autoimmune diseases. The oral pharmacokinetic (PK) parameters and pharmacodynamic effects were established in rodents, and its activity in three models of autoimmune disease (experimental autoimmune encephalitis, 2,4,6‐trinitrobenzenesulfonic acid colitis and CD4+CD45RBhi T cell adoptive transfer colitis) was assessed. RPC1063 demonstrated potent agonist activity of S1P1 receptors. The EC50 values were subnanomolar for S1P1 receptors whether measuring inhibition of cAMP generation (160 ± 60 pM) or [35S]‐ GTPγS binding (410 ± 160 pM; Figure 2A and Table 1). RPC1063 also demonstrated agonist activity at the S1P5 receptor [11 ± 4.3 nM and 83% Emax (percentage of maximum stimulation)]. This represents a 27‐fold selectivity for S1P1 over S1P5 receptors. RPC1063 was specific for S1P1 and S1P5 receptors, induced S1P1 receptor internalization and induced a reversible reduction in circulating B and CCR7+ T lymphocytes in vivo. RPC1063 showed high oral bioavailability and volume of distribution, and a circulatory half‐life that supports once daily dosing. Oral RPC1063 reduced inflammation and disease parameters in all three autoimmune disease models. Br J Pharmacol. 2016 Jun; 173(11): 1778–1792. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867749/

	Solvent	mg/mL	mM
Solubility
	DMSO	20.0	49.40

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 404.46 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Taylor Meadows KR, Steinberg MW, Clemons B, Stokes ME, Opiteck GJ, Peach R, Scott FL. Ozanimod (RPC1063), a selective S1PR1 and S1PR5 modulator, reduces chronic inflammation and alleviates kidney pathology in murine systemic lupus erythematosus. PLoS One. 2018 Apr 2;13(4):e0193236. doi: 10.1371/journal.pone.0193236. PMID: 29608575; PMCID: PMC5880347. 2. Wendt TS, Li YJ, Gonzales RJ. Ozanimod, an S1PR1 ligand, attenuates hypoxia plus glucose deprivation induced autophagic flux and phenotypic switching in human brain VSM cells. Am J Physiol Cell Physiol. 2021 Mar 31. doi: 10.1152/ajpcell.00044.2021. Epub ahead of print. PMID: 33788630. 3. 1. Scott FL, Clemons B, Brooks J, Brahmachary E, Powell R, Dedman H, Desale HG, Timony GA, Martinborough E, Rosen H, Roberts E, Boehm MF, Peach RJ. Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1 ) and receptor-5 (S1P5) agonist with autoimmune disease-modifying activity. Br J Pharmacol. 2016 Jun;173(11):1778-92. doi: 10.1111/bph.13476. Epub 2016 Apr 28. PMID: 26990079; PMCID: PMC4867749. 4. Taylor Meadows KR, Steinberg MW, Clemons B, Stokes ME, Opiteck GJ, Peach R, Scott FL. Ozanimod (RPC1063), a selective S1PR1 and S1PR5 modulator, reduces chronic inflammation and alleviates kidney pathology in murine systemic lupus erythematosus. PLoS One. 2018 Apr 2;13(4):e0193236. doi: 10.1371/journal.pone.0193236. PMID: 29608575; PMCID: PMC5880347.

In vitro protocol:

In vivo protocol:

1. Scott FL, Clemons B, Brooks J, Brahmachary E, Powell R, Dedman H, Desale HG, Timony GA, Martinborough E, Rosen H, Roberts E, Boehm MF, Peach RJ. Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1 ) and receptor-5 (S1P5) agonist with autoimmune disease-modifying activity. Br J Pharmacol. 2016 Jun;173(11):1778-92. doi: 10.1111/bph.13476. Epub 2016 Apr 28. PMID: 26990079; PMCID: PMC4867749. 2. Taylor Meadows KR, Steinberg MW, Clemons B, Stokes ME, Opiteck GJ, Peach R, Scott FL. Ozanimod (RPC1063), a selective S1PR1 and S1PR5 modulator, reduces chronic inflammation and alleviates kidney pathology in murine systemic lupus erythematosus. PLoS One. 2018 Apr 2;13(4):e0193236. doi: 10.1371/journal.pone.0193236. PMID: 29608575; PMCID: PMC5880347.

1: Regueiro M, Siegmund B, Horst S, Moslin R, Charles L, Petersen A, Tatosian D, Wu H, Lawlor G, Fischer M, D'Haens G, Colombel JF. Concomitant Administration of Ozanimod and Serotonergic Antidepressants in Patients With Ulcerative Colitis or Relapsing Multiple Sclerosis. Inflamm Bowel Dis. 2024 Jul 17:izae136. doi: 10.1093/ibd/izae136. Epub ahead of print. PMID: 39018016. 2: Massironi S, Furfaro F, Bencardino S, Allocca M, Danese S. Immunity in digestive diseases: new drugs for inflammatory bowel disease treatment-insights from Phase II and III trials. J Gastroenterol. 2024 Jul 9. doi: 10.1007/s00535-024-02130-x. Epub ahead of print. PMID: 38980426. 3: Favaron A, Abdalla Y, McCoubrey LE, Nandiraju LP, Shorthouse D, Gaisford S, Basit AW, Orlu M. Exploring the interactions of JAK inhibitor and S1P receptor modulator drugs with the human gut microbiome: Implications for colonic drug delivery and inflammatory bowel disease. Eur J Pharm Sci. 2024 Sep 1;200:106845. doi: 10.1016/j.ejps.2024.106845. Epub 2024 Jul 5. PMID: 38971433. 4: Yu B, Jin S, Han J, Xu J, Zhang S, Li Y, Ma X, Wang X, Zhao L. Quantitative evaluation of the time-course and efficacy of targeted agents for ulcerative colitis. Front Pharmacol. 2024 Jun 5;15:1399963. doi: 10.3389/fphar.2024.1399963. PMID: 38903997; PMCID: PMC11188356. 5: Paul D, Swallow E, Patterson-Lomba O, Branchcomb T, N'Dri L, Gomez-Lievano A, Liu J, Dua A, McGinley M. Comparative effectiveness and safety of ozanimod versus other oral DMTs in relapsing-remitting multiple sclerosis: a synthesis of matching-adjusted indirect comparisons. Ther Adv Neurol Disord. 2024 Jun 7;17:17562864241237856. doi: 10.1177/17562864241237856. PMID: 38855023; PMCID: PMC11162124. 6: Yang X, Yan Y, Liu S, Wang Z, Feng X. Potential adverse events associated with sphingosine-1-phosphate (S1P) receptor modulators in patients with multiple sclerosis: an analysis of the FDA adverse event reporting system (FAERS) database. Front Pharmacol. 2024 May 23;15:1376494. doi: 10.3389/fphar.2024.1376494. PMID: 38846098; PMCID: PMC11153721. 7: Kasapoğlu B, Ertan A. Oral small molecule agents in management of ulcerative colitis: fact or fancy? Turk J Med Sci. 2023 Aug 11;53(6):1526-1536. doi: 10.55730/1300-0144.5722. PMID: 38813493; PMCID: PMC10762860. 8: Keenan A, Whichello C, Le HH, Kern DM, Fernandez GS, Turner V, Das A, Quaife M, Ross AP. Patients' Preferences for Sphingosine-1-Phosphate Receptor Modulators in Multiple Sclerosis Based on Clinical Management Considerations: A Choice Experiment. Patient. 2024 May 15. doi: 10.1007/s40271-024-00699-2. Epub ahead of print. PMID: 38748388. 9: Liu E, Chatten K, Limdi JK. Conception, pregnancy and inflammatory bowel disease-Current concepts for the practising clinician. Indian J Gastroenterol. 2024 May 15. doi: 10.1007/s12664-024-01563-9. Epub ahead of print. PMID: 38748381. 10: Sands BE, D'Haens G, Panaccione R, Regueiro M, Ghosh S, Hudesman D, Ahmad HA, Mehra D, Wu H, Jain A, Petersen A, Osterman MT, Afzali A, Danese S. Ozanimod in Patients With Moderate to Severe Ulcerative Colitis Naive to Advanced Therapies. Clin Gastroenterol Hepatol. 2024 May 8:S1542-3565(24)00405-1. doi: 10.1016/j.cgh.2024.03.042. Epub ahead of print. PMID: 38723981. 11: Sankar Kar S, Gharai SR, Sahu SK, Ravichandiran V, Swain SP. The Current Landscape in the Development of Small-molecule Modulators Targeting Sphingosine-1-phosphate Receptors to Treat Neurodegenerative Diseases. Curr Top Med Chem. 2024 Apr 26. doi: 10.2174/0115680266288509240422112839. Epub ahead of print. PMID: 38676503. 12: Jhon GF, Forster EM. Judicious Use of Ozanimod for Ulcerative Colitis and Multiple Sclerosis. ACG Case Rep J. 2024 Apr 15;11(4):e01332. doi: 10.14309/crj.0000000000001332. PMID: 38628167; PMCID: PMC11019820. 13: Nagaraj T, Shinn J, De Felice K. A practical guide to selecting and using new ulcerative colitis therapies. Curr Opin Gastroenterol. 2024 Jul 1;40(4):235-242. doi: 10.1097/MOG.0000000000001023. Epub 2024 Apr 11. PMID: 38606783. 14: Harris S, Feagan BG, Hanauer S, Vermeire S, Ghosh S, Yan J, Wu C, Hu Y, Maddux R, Wolf DC, D'Haens G. Ozanimod Differentially Impacts Circulating Lymphocyte Subsets in Patients with Moderately to Severely Active Crohn's Disease. Dig Dis Sci. 2024 Jun;69(6):2044-2054. doi: 10.1007/s10620-024-08391-z. Epub 2024 Apr 3. PMID: 38568396; PMCID: PMC11162376. 15: Kamyan D, Hassane M, Alnaqbi A, Souid AK, Rasbi ZA, Tahrawi AA, Shamsi MA. Ozanimod-mediated remission in experimental autoimmune encephalomyelitis is associated with enhanced activity of CNS CD27low/- NK cell subset. Front Immunol. 2024 Mar 12;15:1230735. doi: 10.3389/fimmu.2024.1230735. PMID: 38533505; PMCID: PMC10963535. 16: Harnik S, Ungar B, Loebstein R, Ben-Horin S. A Gastroenterologist's guide to drug interactions of small molecules for inflammatory bowel disease. United European Gastroenterol J. 2024 Jun;12(5):627-637. doi: 10.1002/ueg2.12559. Epub 2024 Mar 26. PMID: 38532266; PMCID: PMC11176903. 17: Riley N, Drudge C, Nelson M, Haltner A, Barnett M, Broadley S, Butzkueven H, McCombe P, Van der Walt A, Wong EOY, Merschhemke M, Adlard N, Walker R, Samjoo IA. Comparative efficacy of ofatumumab versus oral therapies for relapsing multiple sclerosis patients using propensity score analyses and simulated treatment comparisons. Ther Adv Neurol Disord. 2024 Mar 23;17:17562864241239453. doi: 10.1177/17562864241239453. PMID: 38525490; PMCID: PMC10960976. 18: Cuffe M, Selinger CP. IBD in women of reproductive age: where do novel therapies fit in? Expert Rev Gastroenterol Hepatol. 2024 Apr- May;18(4-5):129-131. doi: 10.1080/17474124.2024.2334039. Epub 2024 Mar 22. PMID: 38507228. 19: Mirikizumab (Omvoh) for ulcerative colitis. Med Lett Drugs Ther. 2024 Mar 18;66(1698):46-47. doi: 10.58347/tml.2024.1698c. PMID: 38466213. 20: Long-Term Clinical, Endoscopic, and Symptomatic Outcomes of Treatment With Ozanimod: Interim Analysis of the True North Open-Label Extension Study. Gastroenterol Hepatol (N Y). 2023 Dec;19(12 Suppl 9):11-13. PMID: 38445188; PMCID: PMC10910376.