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| 25mg |
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Ponesimod (formerly known as ACT-128800; ACT128800; Ponvory) is an orally bioavailable and selective agonist of sphingosine-1-phosphate receptor 1 (S1PR1, S1P1) approved in 2021 by FDA to treat relapsing forms of multiple sclerosis. In autoimmune diseases mediated by lymphocytes, it is a novel therapeutic approach.
| Targets |
S1PR1 ( IC50 = 6 nM ); S1PR5 ( IC50 = 142 nM ); S1PR4 ( IC50 = 1956 nM ); S1PR3 ( IC50 = 2068 nM )
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|---|---|
| ln Vitro |
Ponesimod stimulates human S1P1-5 uptake, with EC50s of 5.7, >10000, 105, 1108 and 59.1 nM in GTPγS binding assay [2]. Ponesimod stimulates S1P1 reception; for human, relay, and mouse S1P reception, the corresponding EC50 values are 5.7, 1.9, and 1.4 nM [2].
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| ln Vivo |
Ponesimod (30 and 175 mg/kg; once daily, facial, for 8 days) avoids hypersensitivity reactions to sprays that are delayed in type[2]. Ponesimod (30 mg/kg, 3 hours before spraying and 6 hours after adjuvant injection, then 100 mg/kg/day as a food mixture formulation for 18 days) is used in drug formulations to stop adjuvant-induced arthritis[2]. Ponesimod (single wall dose; 0.3-100 mg/kg) Adjacent counts were reduced to 1900/μL after taking ponesimod (100 mg/kg; daily lateral wall gavage for 7 days), and this effect lasted for the full 7 days of the study. Within 48 hours of stopping the perfume, counts went back to baseline levels[2].
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| Enzyme Assay |
In assays for GTPηS binding, membrane preparations from cells expressing human, rat, or mouse recombinant S1P receptors are used. Using IC50 Witch, EC50 values were ascertained. As an external maximum and a minimum for the solvent, the maximal response produced by S1P (the percentage effect of maximal response) was used to express the results as an EC50. The geometric mean and geometric standard deviation of the data are expressed as nanomoles of EC50.
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| Animal Protocol |
Female BALB/c mice (15-25 g) sensitized with DNFB
30 and 175 mg/kg Gavage (30 mg/kg) 19 and 3 h before sensitization, followed by administration as food admix (175 mg/kg/day) for 8 days |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation Although ponesimod is highly bound in maternal plasma and unlikely to reach the breastmilk in large amounts, it is potentially toxic to the breastfed infant. Because there is no published experience with ponesimod during breastfeeding, expert opinion generally recommends that the closely related drug fingolimod should be avoided during breastfeeding, especially while nursing a newborn or preterm infant. However, the manufacturer's labeling does not recommend against the use of ponesimod in breastfeeding. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. |
| References |
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| Additional Infomation |
Ponesimod is a Sphingosine 1-phosphate Receptor Modulator. The mechanism of action of ponesimod is as a Sphingosine 1-Phosphate Receptor Modulator.
See also: Ponesimod (annotation moved to). |
| Molecular Formula |
C23H25CLN2O4S
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|---|---|
| Molecular Weight |
460.97
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| Exact Mass |
460.122
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| Elemental Analysis |
C, 59.93; H, 5.47; Cl, 7.69; N, 6.08; O, 13.88; S, 6.95
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| CAS # |
854107-55-4
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| Related CAS # |
Ponesimod-d4; Ponesimod-d7
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| PubChem CID |
11363176
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| Appearance |
Off-white to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
658.0±65.0 °C at 760 mmHg
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| Flash Point |
351.7±34.3 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.619
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| LogP |
5.08
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
31
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| Complexity |
674
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| Defined Atom Stereocenter Count |
1
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| SMILES |
N(=C1/S/C(=C\C2C=CC(OC[C@H](O)CO)=C(Cl)C=2)/C(=O)N/1C1C=CC=CC=1C)/CCC
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| InChi Key |
LPAUOXUZGSBGDU-ULCCENQXSA-N
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| 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
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| Chemical Name |
(5Z)-5-[[3-chloro-4-[(2R)-2,3-dihydroxypropoxy]phenyl]methylidene]-3-(2-methylphenyl)-2-propylimino-1,3-thiazolidin-4-one
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| Synonyms |
ACT-128800; Ponesimod; ACT 128800; Ponvory; ACT128800
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~92 mg/mL (~199.6 mM)
Ethanol: ~92 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1693 mL | 10.8467 mL | 21.6934 mL | |
| 5 mM | 0.4339 mL | 2.1693 mL | 4.3387 mL | |
| 10 mM | 0.2169 mL | 1.0847 mL | 2.1693 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03232073 | Active Recruiting |
Drug: Ponesimod | Multiple Sclerosis | Actelion | July 5, 2017 | Phase 3 |
| NCT03500328 | Recruiting | Other: Natalizumab, Alemtuzumab, Ocrelizumab, Rituximab, Cladribine, Ofatumumab, Ublituximab-xiiy Other: Glatiramer acetate, Interferons (intramuscular, subcutaneous, pegylated) Teriflunomide, Fumarates (dimethyl, diroximel, monomethyl) Fingolimod, Siponimod, Ozanimod, Ponesimod |
Multiple Sclerosis, Relapsing -Remitting |
Johns Hopkins University | May 2, 2018 | Not Applicable |
| NCT05552196 | Completed | Drug: Ponesimod Drug: Carbamazepine |
Healthy | Janssen Pharmaceutica N.V., Belgium |
October 18, 2022 | Phase 1 |
| NCT02425644 | Completed | Drug: ponesimod Drug: teriflunomide |
Multiple Sclerosis | Actelion | June 4, 2015 | Phase 3 |
| NCT02126956 | Completed | Drug: ACT-128800 | Pharmacokinetics | Actelion | March 2009 | Phase 1 |
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