A-971432

Description: A-971432 is a sphingosine-1-phosphate receptor 5 (S1P5) agonist that is selective for S1P5 over S1P1 and S1P3 (IC50s = 0.006, 0.362, and >10 µM, respectively). It inhibits forskolin-induced cAMP production in CHO cells expressing S1P5 (EC50 = 4.1 nM). A-971432 (1 µM) increases electrical resistance of hCMEC/D3 cells in an in vitro blood-brain barrier model, indicating enhanced barrier integrity, and attenuates blood-brain barrier leakage in an R6/2 transgenic mouse model of Huntington's disease when administered at a dose of 0.1 mg/kg.[1] [2] A-971432 (0.1 mg/kg per day, i.p.) decreases the number of errors made in a horizontal ladder task and increases latency to fall in the rotarod test in R6/2 mice. It also increases spontaneous alternation in the t-maze in aged mice when administered at a dose of 0.1 mg/kg.[1]. Target: Others. Smiles: C(N1CC(C(O)=O)C1)C2=CC=C(OCC3=CC(Cl)=C(Cl)C=C3)C=C2. References: Hobson, A.D., Harris, C.M., van der Kam, E.L., et al. Discovery of A-971432, an orally bioavailable selective sphingosine-1-phosphate receptor 5 (S1P5) agonist for the potential treatment of neurodegenerative disorders. J. Med. Chem. 58(23), 9154-9170 (2015).