SK1-I (BML-258), an analog of sphingosine, is an isozyme-specific competitive SPHK1 inhibitor with a Ki value of 10 μM[1]. SK1-I shows no activity at SPHK1 PKCα, PKCδ, PKA, AKT1, ERK1, EGFR, CDK2, IKKβ or CamK2β. SK1-I enhances autophagy and has antitumor activity[2].
in vivo
Pre-treatment with SK1-I (BML-258; 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].
Significantly lowered baseline mean arterial blood pressure (MAP).
IC 50
SphK1
References
[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. DOI:10.2174/156800910791208599 [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. DOI:10.1080/15548627.2018.1429875 [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. DOI:10.1016/j.ejphar.2018.10.027
