Ponesimod | ACT-128800 | CAS#854107-55-4 | S1P1 immunomodulator

MedKoo Cat#: 206454 | Name: Ponesimod

Description:

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

Ponesimod, also known as ACT-128800, is a potent, and orally active selective S1P(1) agonist. Ponesimod activated S1P(1)-mediated signal transduction with high potency (EC(50) of 5.7 nM) and selectivity. Ponesimod prevented edema formation, inflammatory cell accumulation, and cytokine release in the skin of mice with delayed-type hypersensitivity. Ponesimod also prevented the increase in paw volume and joint inflammation in rats with adjuvant-induced arthritis. Ponesimod may represent a new therapeutic approach in lymphocyte-mediated autoimmune diseases.

Chemical Structure

Ponesimod

CAS#854107-55-4

Theoretical Analysis

MedKoo Cat#: 206454

Name: Ponesimod

CAS#: 854107-55-4

Chemical Formula: C23H25ClN2O4S

Exact Mass: 460.1224

Molecular Weight: 460.97

Elemental Analysis: C, 59.93; H, 5.47; Cl, 7.69; N, 6.08; O, 13.88; S, 6.95

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 3,850.00	Ready to ship
2g	USD 6,450.00	2 Weeks

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Related CAS #

No Data

Synonym

ACT-128800; ACT 128800; ACT128800; Ponesimod.

IUPAC/Chemical Name

(Z)-5-((Z)-3-chloro-4-((R)-2,3-dihydroxypropoxy)benzylidene)-2-(propylimino)-3-(o-tolyl)thiazolidin-4-one

InChi Key

LPAUOXUZGSBGDU-STDDISTJSA-N

InChi Code

InChI=1S/C23H25ClN2O4S/c1-3-10-25-23-26(19-7-5-4-6-15(19)2)22(29)21(31-23)12-16-8-9-20(18(24)11-16)30-14-17(28)13-27/h4-9,11-12,17,27-28H,3,10,13-14H2,1-2H3/b21-12-,25-23-/t17-/m1/s1

SMILES Code

O=C1N(C2=CC=CC=C2C)/C(S/C1=C\C3=CC=C(OC[C@H](O)CO)C(Cl)=C3)=N/CCC

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

Certificate of Analysis

View CoA: current batch, Lot#CRB70419

QC Data

View QC data: current batch, Lot#CRB70419

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Ponesimod (ACT-128800) is a potent and selective agonist of S1P1, with an IC50 of 6 nM, and activates S1P1-mediated signal transduction with high potency (EC50=5.7 nM

In vitro activity:

TBD

In vivo activity:

The effect of preventative and therapeutic ponesimod on the clinical course of MOG-induced acute monophasic EAE was investigated in C57BL/6 mice. Vehicle-treated mice developed fulminant disease with severe clinical signs, which resulted in the death of all animals before Day 24, as indicated by a score of 5 (Figures 1A,1B). Therapeutic treatment with ponesimod resulted in lower overall scores during the chronic phase, compared to vehicle, and a survival rate of 60 percent at the end of the study (Day 31). Preventive treatment resulted in a larger reduction of clinical scores and a 90-percent survival rate. (Figures 1A, 1B). In a follow-up study with reduced overall disease severity (Figure 2A), the effect of ponesimod on cellular infiltration, demyelination, and axonal damage was evaluated in a preventive setting in the brain, spinal cord, and cerebellum (Figure 2B,2C). In the vehicle-treated mice, onset of clinical signs was detected at Day 15 after immunization, reaching a maximal mean clinical score on Day 20. In contrast, mice treated preventively with ponesimod (30mg/kg twice daily from Day 1) were almost completely protected from the onset and progression of EAE. Only one out of the 10 mice treated with ponesimod started to develop minimal disease signs, which began manifesting on Day 26 (Figure 2A). Histological evaluation of the brain, cerebellum, and spinal cord confirmed the observed clinical scores in the respective groups. Compared to vehicle-treated mice, CNS tissues from ponesimod-treated mice revealed few if any inflammatory cell infiltrates, no signs of demyelination, and no apparent axonal damage or loss (Figures 2B, 2C). Prophylactic and therapeutic treatment with ponesimod did not reduce the titer of anti-MOG specific antibodies elicited following the immunization. Reference: Innov Clin Neurosci. 2019 Mar 1; 16(3-4): 22–30. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538399/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	5.0	10.80

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 460.97 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. Pouzol L, Piali L, Bernard CC, Martinic MM, Steiner B, Clozel M. Therapeutic Potential of Ponesimod Alone and in Combination with Dimethyl Fumarate in Experimental Models of Multiple Sclerosis. Innov Clin Neurosci. 2019 Mar 1;16(3-4):22-30. PMID: 31214480; PMCID: PMC6538399. 2. You S, Piali L, Kuhn C, Steiner B, Sauvaget V, Valette F, Clozel M, Bach JF, Chatenoud L. Therapeutic use of a selective S1P1 receptor modulator ponesimod in autoimmune diabetes. PLoS One. 2013 Oct 24;8(10):e77296. doi: 10.1371/journal.pone.0077296. PMID: 24204793; PMCID: PMC3811978.

In vitro protocol:

TBD

In vivo protocol:

1: Juif PE, Hoch M, D'Ambrosio D, Dingemanse J. Biocomparison of Three Formulations of the S1P1 Receptor Modulator Ponesimod in Healthy Subjects. Drugs R D. 2015 Jun;15(2):203-10. doi: 10.1007/s40268-015-0095-7. PubMed PMID: 25939333; PubMed Central PMCID: PMC4488184. 2: Scherz MW, Brossard P, D'Ambrosio D, Ipek M, Dingemanse J. Three different up-titration regimens of ponesimod, an S1P1 receptor modulator, in healthy subjects. J Clin Pharmacol. 2015 Jun;55(6):688-97. doi: 10.1002/jcph.467. Epub 2015 Feb 10. PubMed PMID: 25612299. 3: D'Ambrosio D, Steinmann J, Brossard P, Dingemanse J. Differential effects of ponesimod, a selective S1P1 receptor modulator, on blood-circulating human T cell subpopulations. Immunopharmacol Immunotoxicol. 2015 Feb;37(1):103-9. doi: 10.3109/08923973.2014.993084. PubMed PMID: 25519470. 4: Reyes M, Hoch M, Brossard P, Dingemanse J. Effects of ethnicity and sex on the pharmacokinetics and pharmacodynamics of the selective sphingosine-1-phosphate receptor 1 modulator ponesimod: a clinical study in Japanese and Caucasian subjects. Pharmacology. 2014;94(5-6):223-9. doi: 10.1159/000368837. Epub 2014 Nov 14. PubMed PMID: 25402365. 5: Hoch M, Darpo B, Brossard P, Zhou M, Stoltz R, Dingemanse J. Effect of ponesimod, a selective S1P1 receptor modulator, on the QT interval in healthy individuals. Basic Clin Pharmacol Toxicol. 2015 May;116(5):429-37. doi: 10.1111/bcpt.12336. Epub 2014 Nov 8. PubMed PMID: 25287214. 6: Reyes M, Hoch M, Brossard P, Wagner-Redeker W, Miraval T, Dingemanse J. Mass balance, pharmacokinetics and metabolism of the selective S1P1 receptor modulator ponesimod in humans. Xenobiotica. 2015 Feb;45(2):139-49. doi: 10.3109/00498254.2014.955832. Epub 2014 Sep 4. PubMed PMID: 25188442. 7: Vaclavkova A, Chimenti S, Arenberger P, Holló P, Sator PG, Burcklen M, Stefani M, D'Ambrosio D. Oral ponesimod in patients with chronic plaque psoriasis: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet. 2014 Dec 6;384(9959):2036-45. doi: 10.1016/S0140-6736(14)60803-5. Epub 2014 Aug 10. PubMed PMID: 25127208. 8: Ryan C, Menter A. Ponesimod--a future oral therapy for psoriasis? Lancet. 2014 Dec 6;384(9959):2006-8. doi: 10.1016/S0140-6736(14)61039-4. Epub 2014 Aug 10. PubMed PMID: 25127207. 9: Hoch M, D'Ambrosio D, Wilbraham D, Brossard P, Dingemanse J. Clinical pharmacology of ponesimod, a selective S1P₁ receptor modulator, after uptitration to supratherapeutic doses in healthy subjects. Eur J Pharm Sci. 2014 Oct 15;63:147-53. doi: 10.1016/j.ejps.2014.07.005. Epub 2014 Jul 19. PubMed PMID: 25046167. 10: Krause A, Brossard P, D'Ambrosio D, Dingemanse J. Population pharmacokinetics and pharmacodynamics of ponesimod, a selective S1P1 receptor modulator. J Pharmacokinet Pharmacodyn. 2014 Jun;41(3):261-78. doi: 10.1007/s10928-014-9362-4. Epub 2014 Jun 15. PubMed PMID: 24930034. 11: Olsson T, Boster A, Fernández Ó, Freedman MS, Pozzilli C, Bach D, Berkani O, Mueller MS, Sidorenko T, Radue EW, Melanson M. Oral ponesimod in relapsing-remitting multiple sclerosis: a randomised phase II trial. J Neurol Neurosurg Psychiatry. 2014 Nov;85(11):1198-208. doi: 10.1136/jnnp-2013-307282. Epub 2014 Mar 21. PubMed PMID: 24659797; PubMed Central PMCID: PMC4215282. 12: Brossard P, Scherz M, Halabi A, Maatouk H, Krause A, Dingemanse J. Multiple-dose tolerability, pharmacokinetics, and pharmacodynamics of ponesimod, an S1P1 receptor modulator: favorable impact of dose up-titration. J Clin Pharmacol. 2014 Feb;54(2):179-88. doi: 10.1002/jcph.244. Epub 2014 Jan 9. PubMed PMID: 24408162. 13: Reyes M, Brossard P, Chassard D, Hoch M, Dingemanse J. Effects of ponesimod, a selective S1P1 receptor modulator, on the pharmacokinetics of a hormonal combination contraceptive. Eur J Clin Pharmacol. 2014 Mar;70(3):287-93. doi: 10.1007/s00228-013-1625-2. Epub 2013 Dec 22. PubMed PMID: 24362488. 14: You S, Piali L, Kuhn C, Steiner B, Sauvaget V, Valette F, Clozel M, Bach JF, Chatenoud L. Therapeutic use of a selective S1P1 receptor modulator ponesimod in autoimmune diabetes. PLoS One. 2013 Oct 24;8(10):e77296. doi: 10.1371/journal.pone.0077296. eCollection 2013. PubMed PMID: 24204793; PubMed Central PMCID: PMC3811978. 15: Rey M, Hess P, Clozel M, Delahaye S, Gatfield J, Nayler O, Steiner B. Desensitization by progressive up-titration prevents first-dose effects on the heart: guinea pig study with ponesimod, a selective S1P1 receptor modulator. PLoS One. 2013 Sep 12;8(9):e74285. doi: 10.1371/journal.pone.0074285. eCollection 2013. PubMed PMID: 24069292; PubMed Central PMCID: PMC3771878. 16: Brossard P, Derendorf H, Xu J, Maatouk H, Halabi A, Dingemanse J. Pharmacokinetics and pharmacodynamics of ponesimod, a selective S1P1 receptor modulator, in the first-in-human study. Br J Clin Pharmacol. 2013 Dec;76(6):888-96. doi: 10.1111/bcp.12129. PubMed PMID: 23594176; PubMed Central PMCID: PMC3845312. 17: Piali L, Froidevaux S, Hess P, Nayler O, Bolli MH, Schlosser E, Kohl C, Steiner B, Clozel M. The selective sphingosine 1-phosphate receptor 1 agonist ponesimod protects against lymphocyte-mediated tissue inflammation. J Pharmacol Exp Ther. 2011 May;337(2):547-56. doi: 10.1124/jpet.110.176487. Epub 2011 Feb 23. PubMed PMID: 21345969.