Cenerimod | ACT-334441 | CAS#1262414-04-9 | immunomodulator

MedKoo Cat#: 206431 | Name: Cenerimod

Description:

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

Cenerimod is a potent and orally active immunomodulator, exhibited EC50 value of 2.7 nM. Cenerimod is an agonist for the G protein-coupled receptor S1 P1/EDG1 and has a powerful and long-lasting immunomodulating effect which is achieved by reducing the number of circulating and infiltrating T- and B-lymphocytes, without affecting their maturation, memory, or expansion. Cenerimod may be useful for prevention or treatment of diseases associated with an activated immune system.

Chemical Structure

Cenerimod

CAS#1262414-04-9

Theoretical Analysis

MedKoo Cat#: 206431

Name: Cenerimod

CAS#: 1262414-04-9

Chemical Formula: C25H31N3O5

Exact Mass: 453.2264

Molecular Weight: 453.54

Elemental Analysis: C, 66.21; H, 6.89; N, 9.27; O, 17.64

Price and Availability

Size	Price	Availability
50mg	USD 750.00	2 Weeks
100mg	USD 1,250.00	2 Weeks
200mg	USD 1,950.00	2 Weeks
500mg	USD 3,650.00	2 Weeks
1g	USD 5,250.00	2 Weeks
2g	USD 8,450.00	2 Weeks

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Related CAS #

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Synonym

ACT-334441; ACT334441; ACT 334441; Cenerimod

IUPAC/Chemical Name

(S)-3-(4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)propane-1,2-diol

InChi Key

KJKKMMMRWISKRF-FQEVSTJZSA-N

InChi Code

InChI=1S/C25H31N3O5/c1-4-16-10-18(9-15(2)23(16)32-14-20(30)13-29)24-27-25(33-28-24)19-11-21(17-7-5-6-8-17)26-22(12-19)31-3/h9-12,17,20,29-30H,4-8,13-14H2,1-3H3/t20-/m0/s1

SMILES Code

OC[C@H](O)COC1=C(C)C=C(C2=NOC(C3=CC(C4CCCC4)=NC(OC)=C3)=N2)C=C1CC

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

>2 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

Instruction

View handling instruction

Biological target:

Cenerimod (ACT-334441) is a potent, selective and orally active S1P1 receptor modulator, with an EC50 of 1 nM. Cenerimod shows more than 36‐fold selctivity for hS1P1 over hS1P2, hS1P3, hS1P4, and hS1P5 receptor subtypes (EC50s=>10000, 228, 2134, and 36 nM, respectively).

In vitro activity:

The receptor‐binding profile of cenerimod, (S)‐3‐(4‐(5‐(2‐cyclopentyl‐6‐methoxypyridin‐4‐yl)‐1,2,4‐oxadiazol‐3‐yl)‐2‐ethyl‐6‐methylphenoxy)propane‐1,2‐diol (Figure 1), was evaluated and compared with the activity of the natural ligand S1P20 and the nonselective synthetic S1P receptor agonist pFTY720,21 using (35S)‐GTPγS assays for human recombinant S1P1‐5 receptor subtypes (Table 1). Cenerimod was a highly potent (EC50 = 1 nM) and selective S1P1 receptor agonist, with a 16‐fold higher potency on the S1P1 receptor compared to the natural ligand S1P and similar maximal effect. In contrast to S1P and pFTY720, cenerimod displayed no detectable agonist activity on the S1P2 receptor up to the highest tested concentration (10 μmol·L‐1), which was confirmed in cellular assays (Figure S1). Cenerimod was at least 2000‐fold less active at the S1P3 receptor (EC50 = 228 nmol·L‐1) than S1P (EC50 = 0.1 nmol·L‐1) and 400‐fold less active at the S1P3 receptor than pFTY720 (EC50 = 0.5 nmol·L‐1). Cenerimod displayed weak activity at the S1P4 receptor (EC50 = 2.1 μmol·L‐1) with a 30‐ to 35‐fold lower potency than S1P (EC50 = 60 nmol·L‐1) or pFTY720 (EC50 = 64 nM). Cenerimod was twofold more potent on the S1P5 receptor (EC50 = 36 nmol·L‐1) than the natural ligand S1P (EC50 = 67 nmol·L‐1), but 70‐fold less potent than pFTY720 (EC50 = 0.5 nmol·L‐1). Cenerimod also showed high potency on rat and mouse S1P1 receptors and pronounced selectivity over S1P3 receptors (Table S1). The data demonstrate that cenerimod is a selective S1P1 receptor modulator that exhibits a pronounced selectivity over the S1P2, S1P3, and S1P4 receptor subtypes. Reference: Pharmacol Res Perspect. 2017 Dec;5(6):e00370. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29226621/

In vivo activity:

To investigate whether blockade of S1P1 signaling regulates fibrosis, cenerimod, a selective S1P1 receptor modulator, was orally administered to Scl-cGVHD mice. Cenerimod treatment in both the preventive model (day 0 to day 42) and the therapeutic model (day 22 to day 42) significantly improved alopecia (Fig. 1A) and skin scores compared with the vehicle-treated (control) group (p < 0.01, Fig. 1B). The cenerimod preventive model significantly improved body weight loss, especially from day 18 to day 33, compared with the control group (day18, 21: p < 0.05, day24, 27, 30, 33: p < 0.01, Fig. 1C); however, there was no recovery in body weight loss in the preventive model from day 36 to day 42 compared with the control group. There was no significant difference in body weight loss between cenerimod therapeutic model and the control group. On histopathological analysis, dermal thickness, histopathologic score, trichrome area, and collagen content of the skin were significantly lower in cenerimod-treated groups than in the control group (p < 0.001, Fig. 2A–C,E,F). Furthermore, the fibrotic area and collagen content in the lung were significantly lower in cenerimod-treated groups than in the control group (lung collagen content vehicle vs cenerimod therapeutic model: p < 0.05, lung collagen content vehicle vs cenerimod preventive model: p < 0.01, trichrome area of lung: p < 0.001, Fig. 2D,G). Therefore, cenerimod attenuates skin and lung fibrosis in Scl-cGVHD. Reference: Sci Rep. 2019 Jan 24;9(1):658. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30679645/

	Solvent	mg/mL	mM
Solubility
	DMSO	100.0	220.49

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 453.54 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:

In vitro protocol:

1. Piali L, Birker-Robaczewska M, Lescop C, Froidevaux S, Schmitz N, Morrison K, Kohl C, Rey M, Studer R, Vezzali E, Hess P, Clozel M, Steiner B, Bolli MH, Nayler O. Cenerimod, a novel selective S1P1 receptor modulator with unique signaling properties. Pharmacol Res Perspect. 2017 Dec;5(6):e00370. doi: 10.1002/prp2.370. PMID: 29226621; PMCID: PMC5723703. 2. Kano M, Kobayashi T, Date M, Tennichi M, Hamaguchi Y, Strasser DS, Takehara K, Matsushita T. Attenuation of murine sclerodermatous models by the selective S1P1 receptor modulator cenerimod. Sci Rep. 2019 Jan 24;9(1):658. doi: 10.1038/s41598-018-37074-9. PMID: 30679645; PMCID: PMC6345830.

In vivo protocol:

1: Gerossier E, Nayar S, Froidevaux S, Smith CG, Runser C, Iannizzotto V, Vezzali E, Pierlot G, Mentzel U, Murphy MJ, Martinic MM, Barone F. Cenerimod, a selective S1P1 receptor modulator, improves organ-specific disease outcomes in animal models of Sjögren's syndrome. Arthritis Res Ther. 2021 Nov 29;23(1):289. doi: 10.1186/s13075-021-02673-x. PMID: 34839819; PMCID: PMC8628476. 2: Pérez-Jeldres T, Alvarez-Lobos M, Rivera-Nieves J. Targeting Sphingosine-1-Phosphate Signaling in Immune-Mediated Diseases: Beyond Multiple Sclerosis. Drugs. 2021 Jun;81(9):985-1002. doi: 10.1007/s40265-021-01528-8. Epub 2021 May 13. Erratum in: Drugs. 2021 Aug;81(12):1451. PMID: 33983615; PMCID: PMC8116828. 3: Juif PE, Mueller MS, Charfi H, Dingemanse J. Lack of Effect of Cenerimod, a Selective S1P1 Receptor Modulator, on the Pharmacokinetics of a Combined Oral Contraceptive. Int J Mol Sci. 2022 Nov 29;23(23):14986. doi: 10.3390/ijms232314986. PMID: 36499313; PMCID: PMC9736746. 4: Piali L, Birker-Robaczewska M, Lescop C, Froidevaux S, Schmitz N, Morrison K, Kohl C, Rey M, Studer R, Vezzali E, Hess P, Clozel M, Steiner B, Bolli MH, Nayler O. Cenerimod, a novel selective S1P1 receptor modulator with unique signaling properties. Pharmacol Res Perspect. 2017 Dec;5(6):e00370. doi: 10.1002/prp2.370. PMID: 29226621; PMCID: PMC5723703. 5: Strasser DS, Froidevaux S, Sippel V, Gerossier E, Grieder U, Pierlot GM, Kieninger-Graefitsch A, Vezzali E, Stalder AK, Renault B, Ryge J, Hart A, Mentzel U, Groenen PMA, Keller MP, Trendelenburg M, Martinic MM, Murphy MJ. Preclinical to clinical translation of cenerimod, a novel S1P1 receptor modulator, in systemic lupus erythematosus. RMD Open. 2020 Sep;6(2):e001261. doi: 10.1136/rmdopen-2020-001261. PMID: 32917831; PMCID: PMC7722385. 6: Boof ML, van Lier JJ, English S, Fischer H, Ufer M, Dingemanse J. Absorption, distribution, metabolism, and excretion of cenerimod, a selective S1P1 receptor modulator in healthy subjects. Xenobiotica. 2020 Aug;50(8):947-956. doi: 10.1080/00498254.2020.1736688. Epub 2020 Mar 9. PMID: 32105166. 7: Juif PE, Dingemanse J, Winkle P, Ufer M. Pharmacokinetics and Pharmacodynamics of Cenerimod, A Selective S1P1 R Modulator, Are Not Affected by Ethnicity in Healthy Asian and White Subjects. Clin Transl Sci. 2021 Jan;14(1):143-147. doi: 10.1111/cts.12873. Epub 2020 Sep 10. PMID: 32860737; PMCID: PMC7877840. 8: Kano M, Kobayashi T, Date M, Tennichi M, Hamaguchi Y, Strasser DS, Takehara K, Matsushita T. Attenuation of murine sclerodermatous models by the selective S1P1 receptor modulator cenerimod. Sci Rep. 2019 Jan 24;9(1):658. doi: 10.1038/s41598-018-37074-9. PMID: 30679645; PMCID: PMC6345830. 9: Hermann V, Batalov A, Smakotina S, Juif PE, Cornelisse P. First use of cenerimod, a selective S1P1 receptor modulator, for the treatment of SLE: a double-blind, randomised, placebo-controlled, proof-of-concept study. Lupus Sci Med. 2019 Nov 9;6(1):e000354. doi: 10.1136/lupus-2019-000354. Erratum in: Lupus Sci Med. 2020 May;7(1): PMID: 31798918; PMCID: PMC6861098. 10: Correction: First use of cenerimod, a selective S1P1 receptor modulator, for the treatment of SLE: a double-blind, randomised, placebo- controlled, proof-of-concept study. Lupus Sci Med. 2020 May;7(1):e000354corr1. doi: 10.1136/lupus-2019-000354corr1. Erratum for: Lupus Sci Med. 2019 Nov 9;6(1):e000354. PMID: 32381629; PMCID: PMC7228551. 11: Schlicher L, Kulig P, von Münchow A, Murphy MJ, Keller MP. In Vitro Characterization of Sphingosine 1-Phosphate Receptor 1 (S1P1) Expression and Mediated Migration of Primary Human T and B Cells in the Context of Cenerimod, a Novel, Selective S1P1 Receptor Modulator. Int J Mol Sci. 2022 Jan 21;23(3):1191. doi: 10.3390/ijms23031191. PMID: 35163112; PMCID: PMC8835580. 12: Juif PE, Baldoni D, Reyes M, Wilbraham D, Febbraro S, Vaclavkova A, Hoch M, Dingemanse J. Pharmacokinetics, Pharmacodynamics, Tolerability, and Food Effect of Cenerimod, a Selective S1P₁ Receptor Modulator in Healthy Subjects. Int J Mol Sci. 2017 Dec 6;18(12):2636. doi: 10.3390/ijms18122636. PMID: 29211013; PMCID: PMC5751239. 13: Lott D, Juif PE, Dingemanse J, Krause A. Modelling pharmacokinetics and pharmacodynamics of the selective S1P1 receptor modulator cenerimod in healthy subjects and systemic lupus erythematosus patients. Br J Clin Pharmacol. 2020 Apr;86(4):791-800. doi: 10.1111/bcp.14182. Epub 2020 Jan 14. PMID: 31756016; PMCID: PMC7098867. 14: Krause A, Lott D, Dingemanse J. Estimation of Attainment of Steady-State Conditions for Compounds With a Long Half-Life. J Clin Pharmacol. 2021 Jan;61(1):82-89. doi: 10.1002/jcph.1701. Epub 2020 Jul 12. PMID: 32656870. 15: Juif PE, Ufer M, Dingemanse J. Cardiodynamic Interactions between Two S1P1 Receptor Modulators in an Experimental Clinical Setting: Different Pharmacokinetic Properties as an Opportunity to Mitigate First-Dose Heart Rate Effects. Int J Mol Sci. 2019 Jul 1;20(13):3232. doi: 10.3390/ijms20133232. PMID: 31266149; PMCID: PMC6651405.

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