SK1-​I hydrochloride

Modify Date: 2024-01-08 17:37:28

SK1-​I hydrochloride Structure
SK1-​I hydrochloride structure
Common Name SK1-​I hydrochloride
CAS Number 2366222-05-9 Molecular Weight 313.86
Density N/A Boiling Point N/A
Molecular Formula C17H28ClNO2 Melting Point N/A
MSDS N/A Flash Point N/A

 Use of SK1-​I hydrochloride


SK1-I hydrochloride (BML-258 hydrochloride), an analog of sphingosine, is an isozyme-specific competitive SPHK1 inhibitor with a Ki value of 10 µM[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].

 Names

Name SK1-​I hydrochloride

 SK1-​I hydrochloride Biological Activity

Description SK1-I hydrochloride (BML-258 hydrochloride), an analog of sphingosine, is an isozyme-specific competitive SPHK1 inhibitor with a Ki value of 10 µM[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].
Related Catalog
Target

Ki: 10 µM (SPHK1)[1]

In Vitro 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.
In Vivo 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).
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.

[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.

 Chemical & Physical Properties

Molecular Formula C17H28ClNO2
Molecular Weight 313.86

 Safety Information

Hazard Codes Xi
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