S1P1 agonist 7
S1P1 agonist 7 is a potent, orally active, and β-arrestin-biased S1P1 agonist (EC50(G‑protein) = 12.7 nM and EC50(β‑arrestin) = 3.23 nM). S1P1 agonist 7 demonstrates potent immunomodulatory activity and a favorable safety profile. S1P1 agonist 7 exhibits excellent metabolic stability, minimal to moderate CYP inhibition, and S1P3-sparing selectivity. S1P1 agonist 7 shows pharmacokinetics, effectively reduces circulating lymphocytes, and significantly alleviates disease severity in experimental autoimmune encephalomyelitis (EAE) mouse models under both prophylactic and therapeutic regimens. S1P1 agonist 7 can be used for multiple sclerosis (MS) research.
For research use only. We do not sell to patients.
- Formula: C23H22N2O5
- Molecular Weight:406.43
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
S1P1 agonist 7 (compound 28) shows a 4.51-fold β-arrestin bias relative to Fingolimod (HY-11063) in docking studies, with an EC50 values of 12.7 nM for G-protein signaling and 3.23 nM for β-arrestin recruitment[1].
S1P1 agonist 7 (1-10 µM, 15-60 min) displays high stability across all microsomal species (human, rat, and mouse), and shows no significant inhibition against most CYP isozymes at 10 µM[1].
S1P1 agonist 7 (serial dilution starting from 100 μM, 90 min) demonstrates high selectivity for S1P1 in Chem-4/G₁₅ and CHO-K1 EDG1 cells, exhibiting EC50 values of 0.014 μM in G-protein signaling and 0.0023 μM in β-arrestin recruitment, with only low additional activity at S1P₅[1].
S1P1 agonist 7 (0.041-10 μM, 2 min) does not induce any observable changes in peak frequency or beat rate, even at the highest tested concentrations in human induced pluripotent stem cells (iPSC)-derived cardiomyocytes[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | Note | T1/2 | Tmax | Cmax | AUClast | CL | Vss | F |
|---|---|---|---|---|---|---|---|---|---|---|
| Mice | 1 mg/kg | i.v. | ICR mice | 0.81 h | 0.02 h | 10328.78 ng/mL | 4435.34 ng·h/mL | 3.83 mL/min/kg | 2.27 L/kg | 70.07 % |
| Mice | 10 mg/kg | p.o. | ICR mice | 1.43 h | 1.17 h | 8326.14 ng/mL | 29650.51 ng·h/mL | 5.5 mL/min/kg | 0.67 L/kg | 70.07 % |
S1P1 agonist 7 (10 mg/kg, i.g., daily for 23 days) confers robust protection against EAE in MOG35−55 (HY-P1240) induced EAE mice, moderating its onset, progression, and associated pathological damage[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female C57BL/6N mice (8 weeks old) immunized with MOG/CFA emulsion and received PTX on two consecutive days to induce EAE[1]
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Dosage:10 mg/kg
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Administration:i.g., daily for 23 days
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Result:Delayed disease onset and reduced symptom severity, as indicated by lower cumulative and mean maximum clinical scores.
Maintained its prophylactic effect until the peak of disease severity, which occurred around 17 dpi.
Prevented body weight loss and lowered disease incidence in EAE mice, indicating a protective effect.
Moderated disease progression, and led to a steady reduction in symptom severity until 34 dpi, demonstrating a moderate therapeutic effect comparable to that of Siponimod (HY-12355).
Significantly reduced the cumulative clinical score from 19 dpi (the peak of EAE) to 34 dpi.
Prevented body weight loss compared to the vehicle-treated group.
Markedly reduced demyelination in the spinal cord's dorsal column and ventral white matter.
Reduced immune cell infiltration and partially preserved myelin integrity.
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Animal Model:Female C57BL/6N mice (8 weeks old)[1]
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Dosage:1, 3, and 10 mg/kg
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Administration:i.g., single dose
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Result:Reduced PLC to 24.4 % of baseline at 4 h post administration, outperforming Fingolimod (36.3 %).
Promoted a rapid recovery of PLCs to 70.8 % of baseline within 28 hours, in contrast to Fingolimod (HY-11063), which causes prolonged lymphopenia.
Produced a rapid reduction in lymphocyte counts to approximately 40 % of baseline at 3 h post administration and achieved maximal suppression at the 3 and 10 mg/kg doses by 6 h post administration, while triggering an early rebound in the 1 mg/kg group by the same time, suggesting the onset of recovery.
Elicited a stronger pharmacodynamic response at 3 and 10 mg/kg, and permitted full lymphocyte recovery in all groups within 24 hours.
Chemical Information
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Molecular Weight 406.43
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Formula C23H22N2O5
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SMILES
O=C(O)CCC(N1C=CC2=C1C=CC(OCC3=CC=C(OC(C)C)C(C#N)=C3)=C2)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
S1P1 agonist 7 Related Classifications
HY-175984 Related Classifications
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