SKI 178 是一种有效的鞘氨醇激酶-1 (SphK1) 和 SphK2 抑制剂。 SKI 178 在药物敏感和多药耐药癌细胞系（即 MTR3、NCI-ADR 和 HL60/VCR 细胞）中的 IC50 浓度范围为 1.8 至 0.1 μM 时具有细胞毒性。 SKI 178 在人急性髓细胞白血病细胞系中以 CDK1 依赖性方式诱导细胞凋亡。
| Cas No. | 1259484-97-3 |
| Canonical SMILES | COC1=C(OC)C=CC(/C(C)=N/NC(C2=CC(C3=CC=C(OC)C=C3)=NN2)=O)=C1 |
| 分子式 | C21H22N4O4 |
| 分子量 | 394.4 |
| 溶解度 | DMF: 25 mg/ml,DMSO: 25 mg/ml,DMSO:PBS(pH 7.2) (1:4): 0.2 mg/ml |
| 储存条件 | Store at -20°C |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while. |
| Shipping Condition | Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request |
| 产品描述 | SKI 178 is an inhibitor of sphingosine kinase 1 (SPHK1) and SPHK2. Though previously thought to be selective for SPHK1, cellular thermal shift assay results demonstrate direct target engagement of both SPHK1 and SPHK2 in HEK293 cells overexpressing either SPHK1 or SPHK2. It inhibits SPHK1 by 59.6% when used at a concentration of 10.7 µM and inhibits the production of sphingosine-1-phosphate in A549 cells. SKI 178 is cytotoxic to a variety of cancer cell lines including PANC-1, A549, U251, and MCF-7 cells (IC50s = 0.1, 0.3, 0.5, and 1.3 µM, respectively). It prolongs mitosis and induces cell death through the intrinsic apoptotic pathway in a CDK1-dependent manner. SKI 178 (20 mg/kg every other day) reduces the number of white blood cells to a normal range and increases survival in an MLL-AF9 acute myeloid leukemia (AML) mouse xenograft model. It also destabilizes and inhibits microtubule polymerization in an SPHK-independent manner. |
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