SLM6031434 jest selektywnym inhibitorem kinazy sfingozyny (Sph) 2 (SK2, SphK2, SpK2) (r/m SphK2 Ki = 400/500 nM, r/m SphK1 Ki >20 μM), który skutecznie obniża komórkowy poziom 1-fosforanu sfingozyny (S1P) (47% S1P & 143% Sph kontroli w U937 po 2-godzinnym leczeniu 100 nM SLM6031434) i selektywnie zmniejsza S1P w osoczu u myszy Sphk1-/-, ale nie Sphk2-/- in vivo (5 mg/kg i.v.). W przeciwieństwie do myszy Sphk2-KO, leczenie SLM6031434 zwiększa S1P w osoczu u myszy typu dzikiego i zapewnia skuteczność neuroprotekcyjną przed udarem niedokrwiennym (2 mg/kg i.v. 2 godziny przed tMCAO).
Selektywny inhibitor kinazy sfingozynowej 2 (SK2, SphK2, SpK2) o skuteczności neuroprotekcyjnej przeciwko udarowi niedokrwiennemu in vivo.
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The Journal of pharmacology and experimental therapeutics, 355(1), 23-31 (2015-08-06)
Sphingosine 1-phosphate (S1P) levels are significantly higher in blood and lymph than in tissues. This S1P concentration difference is necessary for proper lymphocyte egress from secondary lymphoid tissue and to maintain endothelial barrier integrity. Studies with mice lacking either sphingosine
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