SLM6031434 is an inhibitor of sphingosine kinase 2 (SPHK2) (K = 0.4 μM for the recombinant mouse enzyme). It is selective for SPHK2 over SPHK1 (Ks = >20 μM). It decreases sphingosine-1-phosphate (S1P; ) and increases sphingosine levels in U937 monocytic leukemia cells in a concentration-dependent manner. SLM6031434 (5 mg/kg) reduces blood S1P levels in Sphk1, but not Sphk2, mice. SLM6031434 also increases blood S1P levels in wild-type mice and rats.
SLM6031434 (hydrochloride) is the hydrochloride salt form of SLM6031434. SLM6031434 is a highly selective sphingosine kinase 2 (SphK2) inhibitor with an IC50 value of 0.4 μM for SphK2. SLM6031434 exerts anti-fibrotic effects by increasing sphingosine accumulation and Smad7 expression. SLM6031434 demonstrates effective anti-fibrotic efficacy in a unilateral ureteral obstruction (UUO)-induced tubulointerstitial fibrosis mouse model. SLM6031434 can be used for the study of proteinuric kidney diseases or chronic kidney disease (CKD)
IC50&Target
SphK2 SphK1
0.4 μM (IC50) 16 μM (IC50)
体外研究
SLM6031434 (3 μM, 16 h) reduces the expression of TGFβ-induced profibrotic markers (Col1, FN-1, CTGF) in primary mouse renal fibroblasts.
SLM6031434 (0.3-10 μM, 16 h) dose-dependently increased Smad7 protein expression in primary mouse renal fibroblasts.
SLM6031434 (1 μM, 20 h) significantly increased the ceramide levels in human podocytes .
SLM6031434 (1 μM, 24 h) upregulates the protein and mRNA expression of nephrin and Wilms tumor suppressor gene 1 (WT1) in wild-type human podocytes.
体内研究
SLM6031434 (5 mg/kg, intraperitoneal injection, daily, 9 days) alleviates renal interstitial fibrosis induced by unilateral ureteral obstruction in mice.
Animal Model:
UUO-induced renal interstitial fibrosis mouse models were established by performing unilateral ureteral ligation surgery on 10-12 week-old adult male mice
Dosage:
5 mg/kg
Administration:
i.p., daily, 9 days
Result:
Reduced collagen accumulation and ECM deposition.
Decreased α-SMA expression to reduce myofibroblast activation.
Downregulated mRNA and protein levels of Col1, FN-1, CTGF.
Increased sphingosine accumulation and Smad7 expression, while reduced Smad2 phosphorylation.
Reduced F4/80-positive macrophage infiltration and downregulated iNOS, Mcr1 mRNA.
分子式
C22H30F3N5O2.HCl
分子量
489.96
CAS号
1897379-34-8
运输条件
Room temperature in continental US; may vary elsewhere.