| Identification | Back Directory | [Name]
ceralifimod | [CAS]
891859-12-4 | [Synonyms]
ONO-4641
ceralifimod
Ceralifimod (ONO-4641)
Ceralifimod (Synonyms: ONO-4641)
3-Azetidinecarboxylic acid, 1-[[3,4-dihydro-6-[(2-methoxy-4-propylphenyl)methoxy]-1-methyl-2-naphthalenyl]methyl]- | [Molecular Formula]
C27H33NO4 | [MDL Number]
MFCD28502037 | [MOL File]
891859-12-4.mol | [Molecular Weight]
435.56 |
| Chemical Properties | Back Directory | [Boiling point ]
595.9±50.0 °C(Predicted) | [density ]
1.172±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO:5.0(Max Conc. mg/mL);11.48(Max Conc. mM) | [form ]
A crystalline solid | [pka]
2.71±0.20(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Description]
Ceralifimod is an agonist of the sphingosine-1-phosphate (S1P) receptors S1P1 and S1P5 (Kis = 0.626 and 0.574 nM, respectively). It is selective for S1P1 and S1P5 over S1P2-4 (Kis = >5,450, >5,630, and 28.8 nM, respectively). Ceralifimod induces calcium influx in CHO-K1 cells overexpressing S1P1 (EC50 = 1 nM) and cAMP accumulation in CHO-K1 cells overexpressing S1P1 or S1P5 (EC50s = 0.027 and 0.33 nM, respectively). In vivo, ceralifimod (0.03 and 0.1 mg/kg) reduces paw edema in a rat model of collagen induced arthritis (CIA). It also delays disease onset and inhibits lymphocyte infiltration of the spinal cord in a rat model of experimental autoimmune encephalomyelitis (EAE) and prevents disease relapse in a non-obese diabetic mouse model of relapsing-remitting EAE. | [Uses]
Ceralifimod (ONO-4641) is selective, high potent agonist for sphingosine 1-phosphate receptors 1 and 5, with EC50s of 27.3, 334 pM for human S1P receptor 1 and 5, respectively. | [in vivo]
The clinical scores of the Ceralifimod (ONO-4641) 0.03 and 0.1 mg/kg groups remain lower than that in the control group. The maximum clinical scores decrease dose-dependently in the Ceralifimod (ONO-4641) groups and those in the Ceralifimod (ONO-4641) 0.03 and 0.1 mg/kg groups are significantly lower than that in the control group. Specifically, paralysis is inhibited completely in seven of eight animals in the Ceralifimod (ONO-4641) 0.1 mg/kg group.
In normal NOD mice, the number of peripheral blood lymphocytes is decreased by approximately 20, 60 and 80% at 24 h after a single oral dose of 0.01, 0.03 and 0.1 mg/kg of Ceralifimod (ONO-4641), respectively. In the control group of the NOD mouse model of relapsing-remitting EAE, the relapse rate is 90.0%, and two of the nine animals die. The cumulative clinical score in the control group is 65.4±18.50. In contrast, none of animals in the Ceralifimod (ONO-4641) 0.1 mg/kg group have a relapse; that is, Ceralifimod completely prevents relapse at a dose of 0.1 mg/kg. In the Ceralifimod (ONO-4641) groups, two of the nine animals in the 0.01 mg/kg die[1]. | [storage]
Store at -20°C | [References]
[1] Komiya T, et al. Efficacy and immunomodulatory actions of ONO-4641, a novel selective agonist for sphingosine 1-phosphate receptors 1 and 5, in preclinical models of multiple sclerosis. Clin Exp Immunol. 2013 Jan;171(1):54-62. DOI:10.1111/j.1365-2249.2012.04669.x |
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BOC Sciences
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1-631-485-4226; 16314854226 |
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https://www.bocsci.com |
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