HWG-35D is a potent, selective sphingosine kinase 2 (SphK2, SK2) with IC50 of 41 nM, 100-fold selectivity for SK2 over SK1.
HWG-35D (0-500 nM) did not alter either SK1 or dihydroceramide desaturase 1 (DES1) protein expression in either human or murine cells, HWG-35D (300 nM) did not decrease SK1 protein levels in total CD4+ T cells isolated from mouse spleen.
HWG-35D topical application reduced psoriasis-like skin symptoms induced by imiquimod (IMQ), normalized the serum interleukin-17A levels elevated by IMQ.
HWG-35D also decreased skin mRNA levels of interleukin-17A, K6 and K16 genes induced by IMQ, blocked T helper type 17 differentiation of naïve CD4+ T cells with concomitant reduction of SOCS1.
HWG-35D dose-dependently increased Smad7 expression and ameliorated the expression of Col1, FN-1 and CTGF in primary renal fibroblasts.
HWG-35D demonstrated anti-fibrotic potential in unilateral ureter obstruction (UUO), a model for progressive renal fibrosis.