SK1-I hydrochloride (BML-258 hydrochloride) 是鞘氨醇的类似物，是同功酶特异性 SPHK1 竞争抑制剂，Ki 值为 10181M。SK1-I hydrochloride 对 SPHK2，PKCα，PKCδ，PKA，AKT1，ERK1，EGFR，CDK2，IKKβ 或 CamK2β 无活性。SK1-I hydrochloride 增强自噬并具有抗肿瘤活性。
货号:ajcx32916
CAS:2366222-05-9
分子式:C17H28ClNO2
分子量：313.86
溶解度:DMSO : 250 mg/mL (796.53 mM)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

SK1-I hydrochloride (BML-258 hydrochloride), an analog of sphingosine, is an isozyme-specific competitive SPHK1 inhibitor with a Ki value of 10 &#181M[1]. SK1-I hydrochloride shows no activity at SPHK1 PKCα, PKCδ, PKA, AKT1, ERK1, EGFR, CDK2, IKKβ or CamK2β. SK1-I hydrochloride enhances autophagy and has antitumor activity[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].

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].

[1]. Melissa R Pitman, et al. Inhibitors of the sphingosine kinase pathway as potential therapeutics. Curr Cancer Drug Targets. 2010 Jun;10(4):354-67.
[2]. Santiago Lima, et al. TP53 is required for BECN1- and ATG5-dependent cell death induced by sphingosine kinase 1 inhibition. Autophagy. 2018;14(6):942-957.
[3]. Fiona H Greig, et al. Requirement for sphingosine kinase 1 in mediating phase 1 of the hypotensive response to anandamide in the anaesthetised mouse. Eur J Pharmacol. 2019 Jan 5;842:1-9.