SK1-I hydrochloride (BML-258 hydrochloride) is a sphingosine analog that can enhance autophagy and has antitumor activity. SK1-I hydrochloride is an isozyme-specific competitive SPHK1 inhibitor (Ki = 10 μM) [1] [2].

SK1-I hydrochloride (0-10 μM; 24 hours) attenuates cancer cell growth and survival in a TP53-dependent manner in HCT116 cells and HCT116 cells bearing TP53 null cancer [2]. SK1-I hydrochloride (0-20 μM; 12 hours) induces more CASP3 cleavage in HCT116 cells, compared to HCT116 cells lacking TP53, leading to a hallmark of apoptosis [2]. Cell Viability Assay [2] Cell Line: HCT116 cells and HCT116 cells bearing TP53 null cancer Concentration: 0 μM, 2.5 μM, 5 μM, 7.5 μM, 10 μM Incubation Time: 24 hours Result: Decreased cancer cell growth and survival. Western Blot Analysis [2] Cell Line: HCT116 cells and HCT116 cells bearing TP53 null cancer Concentration: 0 μM, 5 μM, 10 μM, 20 μM Incubation Time: 12 hours Result: Induced more CASP3 cleavage in HCT116 cells, compared to HCT116 cells lacking TP53.

Pre-treatment with SK1-I hydrochloride (BML-258 hydrochloride; intraperitoneal (i.p.) injection; once; 24 hours prior to baseline mean arterial blood pressure (MAP) measurement; 75 mg/kg) before anandamide (i.v. injection; two doses; 1 and 10 mg/kg) significantly decreases the hypotensive response [3]. Animal Model: Male C57BL/6 mice (24 ± 3.5 g) [3] Dosage: 75 mg/kg Administration: Intraperitoneal (i.p.) injection; once; 24 hours prior to baseline MAP measurement Result: Significantly lowered baseline mean arterial blood pressure (MAP).