Amiselimod

Amiselimod (MT-1303) is converted to its active metabolite Amiselimod phosphate by sphingosine kinases in vivo. Amiselimod is an orally active and high selectivity sphingosine 1-phosphate receptor-1 (S1P1) agonist, designed to reduce the bradycardia effects associated with fingolimod and other S1P receptor modulators. Amiselimod inhibits chronic colitis via inhibiting infiltration of colitogenic Th1 and Th17 cells into the colon. Amiselimod inhibits lupus nephritis by reducing the infiltration of autoreactive T cells into the kidneys. Amiselimodis promising for research of autoimmune diseases^[1][2][3][4]. In Vitro:Amiselimod (100 nM, 12 h) is converted into Amiselimod-P in HEK293 cells or primary HCMs (human cardiac myocytes) more slowly than Fingolimod (HY-11063) was converted into fingolimod-P^[1].
Amiselimod-P (0.001-1000 nM) shows agonist activity at S1P1 receptor with an EC₅₀ of 75 pM, and is more potent than at S1P4 and S1P5 receptors but has no distinct agonist activity at S1P2 or S1P3 receptors in human S1P receptor-expressing cells^[1].
Amiselimod-P (0.001-1000 nM) increases G-protein-activated inwardly rectifying potassium (GIRK) current amplitude in a concentration-dependent manner, with an EC₅₀ of 41.6 nM in human atrial myocytes^[1].
In Vivo:Amiselimod (1 mg/kg, p.o.,) converts into Amiselimod-P which is lower in rat heart tissue than fingolimod-P, potentially contributing to the minimal cardiac effects ^[1].
Amiselimod (0.3-30 mg/kg, p.o., with a 6 day interval between vehicle and 0.3 mg/kg, 13 or 14 day intervals between dose levels of 0.3, 3 and 30 mg/kg) hydrochloride does not affect heart rate or ECG parameters in monkeys^[1].
Amiselimod (0.3 mg/kg, p.o., daily, 3 days) decreases S1P1 expression on CD4⁺ T cells from mesenteric lymph nodes in C57BL/6 mice^[3].
. Amiselimod (0.3 mg/kg, p.o., daily, 28 days) inhibits the development of colitis induced by adoptive transfer of CD4⁺CD45RB^high T cells in SCID mice^[3].
Amiselimod (0.3 mg/kg, p.o., daily, 3-4 weeks) reduces infiltration of Th1 and Th17 cells into the colon of colitis mic e induced by adoptive transfer of CD4⁺CD45RB^high T cells ^[3].
Amiselimod (0.1-0.3 mg/kg, p.o., daily, 21 days) inhibits the development of chronic colitis with an efficacy comparable to that of an anti-mTNF-α mAb (250 μg/mouse) in adoptive transfer of CD4⁺CD45RB^high T cells induced colitis mice^[3].
Amiselimod (0.1-1 mg/kg, p.o., daily, 18 weeks) strongly inhibits the development of lupus nephritis in MRL/lpr mice^[4].
Amiselimod (0.1-0.3 mg/kg, p.o., daily, 10 weeks) prevents progression of lupus nephritis in NZBWF1 Mice^[4].
Amiselimod (0.3 mg/kg, p.o., daily, 13 weeks) reduces infiltration of T Cells into the kidneys of NZBWF1 mice^[4].