Orally active, highly S1P1 subtype-selective sphingosine-1-phosphate (S1P) receptor antagonist with in vitro and in vivo efficacy.
TASP0277308 is an orally active, highly S1P1 subtype-selective sphingosine-1-phosphate (S1P) receptor antagonist (IC50 = 2.7/4.2 nM against 0.1 nM S1P for binding mouse/human S1P1; IC50 >8.7 μM for S1P2-5). TASP0277308 effectively inhibits S1P1-mediated GTPγS membrane binding, cAMP response and chemotaxis (IC50 = 7.8, 3.5, 15 nM, respectively, agianst 10 nM S1P; hS1P1-expressing HEK293 or CHO) and demonstrates in vivo efficacy in various animal disease models, including collagen-induced arthritis and tumor angiogenesis in mice (10-100 mg/kg bid po), as well as neuropathic pain in rats (0.6-3 mg/kg via acute po or ip, acute 30 nmol or daily 10 nmol intrathecal injection).
Sphingosine-1-phosphate receptor 1 activation in astrocytes contributes to neuropathic pain
Proceedings of the National Academy of Sciences of the USA, 116(21), 10557-10562 (2019)
S1P1 Modulator-Induced G ?i Signaling and ?-Arrestin Recruitment Are Both Necessary to Induce Rapid and Efficient Reduction of Blood Lymphocyte Count In Vivo
Molecular Pharmacology, 93(2), 109-118 (2018)
Blocking S1P interaction with S1P? receptor by a novel competitive S1P?-selective antagonist inhibits angiogenesis
Biochemical and Biophysical Research Communications, 419(4), 754-760 (2012)
Amelioration of collagen-induced arthritis by a novel S1P1 antagonist with immunomodulatory activities
Journal of immunology (Baltimore, Md. : 1950), 188(1), 206-215 (2012)
Targeting the S1P/S1PR1 axis mitigates cancer-induced bone pain and neuroinflammation
Il team dei nostri ricercatori vanta grande esperienza in tutte le aree della ricerca quali Life Science, scienza dei materiali, sintesi chimica, cromatografia, discipline analitiche, ecc..
