Ozanimod

Biological Activity

In vitro: In S1P1R-HEK293T cells, Ozanimod induces sustained S1P1R internalization and degradation. In vivo: In vivo, Ozanimod shows high oral bioavailability and volume of distribution. In a MOG-induced EAE mouse model, Ozanimod (3 mg/kg, p.o.) suppresses clinical symptoms. In a rat TNBS model of inflammatory bowel disease, Ozanimod (1.2 mg/kg, p.o.) inhibits clinical and histological disease scores. In a Naïve CD4+CD45Rbhi T cell adoptive transfer model, Ozanimod (1.2 mg/kg, p.o.) also significantly reduced disease severity as assessed by measuring the degree of inflammation, gland loss, hyperplasia, neutrophil infiltrate and mucosal thickness.

Protocol

Cell Experiment
Cell lines
Preparation method
Concentrations
Incubation time

Animal Experiment
Animal models	MOG-induced EAE model in C57Bl6 mice, TNBS model of inflammatory bowel disease in male Sprague Dawley rats, and Na飗e CD4+CD45Rbhi T cell adoptive transfer model in SCID mice
Formulation	5% DMSO, 5% Tween-20, 90% 0.1N HCl
Dosages	0.1-3 mg/kg
Administration	p.o.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information

References

Ozanimod Induction and Maintenance Treatment for Ulcerative Colitis.
Sandborn WJ, et al. N Engl J Med. 2016 May 5;374(18):1754-62. PMID: 27144850.

Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1 ) and receptor-5 (S1P5 ) agonist with autoimmune disease-modifying activity.
Scott FL, et al. Br J Pharmacol. 2016 Jun;173(11):1778-92. PMID: 26990079.