AKP-11 is an agonist of sphingosine-1-phosphate receptor 1 (S1P) with an EC value of 0.047 μM for [S]GTPγS binding to CHO-K1 cell membranes expressing the human receptor. It decreases surface expression of S1P and increases phosphorylation of Akt and ERK in CHO cells expressing S1P-HA when used at a concentration of 100 nM. AKP-11 (1.3 and 3 mg/kg) reduces protein levels of IFN-γ and IL-17 in spinal cord tissue and decreases disease severity in a rat model of experimental autoimmune encephalomyelitis (EAE). It decreases peripheral counts of total lymphocytes and total, CD4, CD8, and CD26L T cells in an EAE rat model, as well as in healthy control animals, when administered at a dose of 1.3 mg/kg.
AKP-11 (S1P1 Agonist 1) is a S1P1 agonist with immunomodulatory activities.
IC50&Target
S1P1
体外研究
AKP-11 (S1P1 Agonist 1) binds to S1P1 is internalized and activates intracellular AKT and ERKs cellular signaling pathways.
AKP-11 (S1P1 Agonist 1) mediated S1P1 downregulation is independent of sphingosine kinase activity indicating it to be a direct agonist of S1P1.
AKP-11 (S1P1 Agonist 1) decreases cell surface expression of S1P1 in in vitro cell culture mode.
体内研究
AKP-11 (S1P1 Agonist 1) (1.3mg/kg) attenuates EAE disease. EAE is the animal model of multiple sclerosis which is extensively used for investigating clinical studies for multiple sclerosis drugs. AKP-11 (S1P1 Agonist 1) treatment reduces peripheral total blood lymphocyte and T lymphocyte counts significantly. The reduction in total lymphocytes and T cells are 48% and 41% in AKP11 treated animals, respectively. The reduction in the CD4+ and CD8+ T cell populations are 41% and 40% in S1P1 Agonist 1 treated animals, respectively. AKP-11 (S1P1 Agonist 1)treatment reduces CNS infiltration of T cells and Cytokines and enhances neuroprotection. AKP-11 (S1P1 Agonist 1) treatment has little effect on the heart rate of animals. The decrease in blood pressure is also smaller with S1P1 Agonist 1 treatment as compared animals treated with FTY720.
分子式
C22H22ClN3O5
分子量
443.88
CAS号
1220973-37-4
中文名称
AKP-11
运输条件
Room temperature in continental US; may vary elsewhere.