[CAS NO. 2366222-05-9] SK1-Ihydrochloride
PRODUCTS SPECIFICATIONS [2366222-05-9]
DESCRIPTION [2366222-05-9]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 313.86 |
| Molecular Formula | C17H28ClNO2 |
| SMILES | OC[C@H]([C@H](/C=C/C1=CC=C(C=C1)CCCCC)O)NC.[H]Cl |
1 Publications Citing Use of MCE
Summary
SK1-I hydrochloride (BML-258 hydrochloride), an analog of sphingosine, is an isozyme-specific competitive SPHK1 inhibitor with a K i 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] .
IC50 & Target
|
SphK1 |
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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| 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). |
Appearance
Liquid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : 250 mg/mL ( 796.53 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 3.1861 mL | 15.9307 mL | 31.8613 mL |
| 5 mM | 0.6372 mL | 3.1861 mL | 6.3723 mL |
| 10 mM | 0.3186 mL | 1.5931 mL | 3.1861 mL |
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.