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Ozanimod hydrochloride

CAS No. : 1618636-37-5

MCE 站：Ozanimod hydrochloride

产品活性：Ozanimod (hydrochloride) (RPC-1063) 是一种鞘氨醇1-磷酸 (S1P) 受体调节剂，可高亲和力地选择性结合 S1P 受体亚型 1 (S1P1) 和 S1P5 (S1P5)。Ozanimod (hydrochloride) (RPC-1063) 对 hS1P₁和hS1P₅ 受体具有调节作用，EC₅₀ 值分别为1.03 nM 和 8.6 nM。Ozanimod (hydrochloride) (RPC-1063) 可用于复发性多发性硬化 (MS) 的研究。

研究领域：GPCR/G Protein

作用靶点：LPL Receptor

In Vitro: Ozanimod (hydrochloride) (RPC-1063) has potency ａnd intrinsic activity of S1P receptor modulators for S1P5 across species with [³⁵S]-GTPgS binding, ａnd the EC₅₀ values of 1.03 nM, 1.29 nM, 0.90 nM, 1.02 nM ａnd 0.61 nM for Human S1P₁, Cynomolgus monkey S1P₁, Mouse S1P₁, Rat S1P1 ａnd Canine S1P₁, respectively; ａnd the EC₅₀ values of 8.6 nM, 15.9 nM, 957.5 nM, 2032.7 nM ａnd 1662.0 nM for Human S1P₅, Cynomolgus monkey S1P₅, Mouse S1P₅, Rat S1P₅ ａnd Canine S1P₅, respectively.
Ozanimod (hydrochloride) (RPC-1063) restores the potency with EC₅₀ from 958 nM for mS1P₅ to 6.7 nM for mS1P₅_A120T to closely mirror the EC₅₀ for hS1P₅ of 8.6 nM by mutating the alanine in the mouse sequence.
Ozanimod (hydrochloride) (RPC-1063) has binding affinity with K_i values of 2.0 nM, 59.9 nM ａnd 5.6 nM for hS1P₅, mS1P₅ ａnd mS1P₅ _A120T, respectively.
Ozanimod (hydrochloride) (RPC-1063) has saturation binding of [³H]-ozanimod to hS1P₅, ａnd mS1P₅_A120T with K_D values of 6.56 nM, 7.35 nM, respectively ａnd also has saturation binding for [³H]-A971432 to S1P₅D value of 8.75 nM.

In Vivo: Ozanimod (hydrochloride) (RPC-1063) (oral gavage; 0.05, 0.2, or 1 mg/kg; once daily; for 14 consecutive days) exposures sufficient to engage S1P₁, but not S1P₅, resulted in reduced circulating lymphocytes, disease scores, ａnd body weight loss; reduced inflammation, demyelination, ａnd apoptotic cell counts in the spinal cord; ａnd reduced circulating levels of the neuronal degeneration marker, neurofilament light.
Ozanimod (hydrochloride) (RPC-1063) (oral gavage; 5 mg/kg; once-daily) prevented axonal degradation ａnd myelin loss during toxin challenge but did not facilitate enhanced remyelination after intoxication.
Ozanimod (hydrochloride) (RPC-1063) (oral, 1 or 5 mg/kg, for 7 days) .

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