K145 |
رقم الكتالوجGC12581
One-Click Copy Product Info
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K145 هو مثبط انتقائي ، ومنافس للركيزة ونشط شفويا من SphK2 مع IC50 4.3 ميكرومتر و Ki من 6.4 ميكرومترK145 غير فعال ضد SphK1 وأنواع البروتين الأخرىيحفز K145 موت الخلايا المبرمج وله نشاط مضاد للأورام
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1309444-75-4
Sample solution is provided at 25 µL, 10mM.
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K145 is a selective sphingosine kinase 2 (SphK2) inhibitor with an IC50 value of 4.3μM and a Ki value of 6.4μM, exhibiting anticancer activity[1, 2]. K145 inhibits SphK2 activity by competitively binding to it, without affecting the homologous enzyme SphK1[3]. K145 can inhibit the growth of solitary plasmacytoma (SP) cells[4].
In vitro, pretreatment of breast cancer cells (MCF-7, MDA-MB-231, and LM2-4 cells) with K145 (2μM) significantly inhibited epidermal growth factor (EGF)-mediated cell migration and significantly reduced sphingosine-1-phosphate (S1P) levels in LM2-4 cells[5].
In vivo, K145 (5, 10mg/kg) administered via intraperitoneal injection for 10 days in ob/ob and db/db mice reduced hepatic lipid accumulation and lowered fasting blood glucose levels in db/db mice, and regulated the mRNA levels of lipid metabolism-related genes in the liver of ob/ob mice[6]. K145 (50mg/kg/day) administered via intraperitoneal injection for 30 days in glioblastoma (GBM) cell xenograft mice slowed tumor growth and increased mouse survival rate[7].
References:
[1] Liu K, Guo T L, Hait N C, et al. Biological characterization of 3-(2-amino-ethyl)-5-[3-(4-butoxyl-phenyl)-propylidene]-thiazolidine-2, 4-dione (K145) as a selective sphingosine kinase-2 inhibitor and anticancer agent[J]. PloS one, 2013, 8(2): e56471.
[2] Lewis A C, Wallington-Beddoe C T, Powell J A, et al. Targeting sphingolipid metabolism as an approach for combination therapies in haematological malignancies[J]. Cell Death Discovery, 2018, 4(1): 72.
[3] Worrell B L, Brown A M, Santos W L, et al. In silico characterization of structural distinctions between isoforms of human and mouse sphingosine kinases for accelerating drug discovery[J]. Journal of chemical information and modeling, 2019, 59(5): 2339-2351.
[4] Li J, Li X J, Zhao D, et al. K145, a sphingosine kinase 2 inhibitor, inhibits solitary plasmacytoma cell growth[J]. The FASEB Journal, 2018, 32: 836.14-836.14.
[5] Maiti A, Takabe K, Hait N C. Metastatic triple-negative breast cancer is dependent on SphKs/S1P signaling for growth and survival[J]. Cellular signalling, 2017, 32: 85-92.
[6] Shi Y, Wei Q, Liu Y, et al. The alleviating effect of sphingosine kinases 2 inhibitor K145 on nonalcoholic fatty liver[J]. Biochemical and biophysical research communications, 2021, 580: 1-6.
[7] Fei X, Dou Y, Sun K, et al. TRIM22 promotes the proliferation of glioblastoma cells by activating MAPK signaling and accelerating the degradation of Raf-1[J]. Experimental & molecular medicine, 2023, 55(6): 1203-1217.
| Cell experiment [1]: | |
Cell lines | MCF-7、MDA-MB-231、LM2-4 cells |
Preparation Method | Cells were maintained in 1-2% serum containing medium for 18h. The monolayers were carefully scratched using a 20-μl or 200-μl pipette tip. The cellular debris was subsequently removed by washing with PBS, and the cells were incubated in medium with 1-2% serum. Cells were pre-treated with 2μM PF543 (SphK1 inhibitor), and K145 (SphK2 inhibitor before treatment of epidermal growth factor (EGF) (100ng/ml) for 8 to 24h. Migrating cells into the wounded area were photographed under a phase contrast microscope. |
Reaction Conditions | 2µM; 8, 24h |
Applications | Inhibiting SphK2 with compound K145 not only suppresses EGF-mediated migration of MCF-7 and MDA-MB-231 cells, but also significantly inhibits EGF-mediated migration of the lung metastatic breast cancer cell line LM2-4. |
| Animal experiment [2]: | |
Animal models | Male C57BL/6, leptin deficient ob/ob mice, db/db mice |
Preparation Method | 13 weeks male C57BL/6, leptin deficient ob/ob mice and db/db mice were maintained in a room of 12-h light-dark cycle with temperature-controlled at 25℃. Six mice were used in each group and received i.p. injection of SphK2 inhibitor K145 at dosage of 5mg/kg and 10mg/kg (dissolved in DMSO) everyday as experimental group. For control group, mice received equivalent DMSO i.p. injection. After injection for 10 days, their blood and liver samples were collected. |
Dosage form | 5, 10mg/kg; 10 days; i.p. |
Applications | K145 ameliorated fatty liver of ob/ob mice. K145 ameliorated hepatic lipid accumulation and fasting blood glucose of db/db mice. Hepatic mRNA levels for Lipid metabolism related genes were regulated by K145 treatment of ob/ob mice. |
References: | |
| Cas No. | 1309444-75-4 | SDF | |
| Chemical Name | (Z)-3-(2-aminoethyl)-5-(3-(4-butoxyphenyl)propylidene)thiazolidine-2,4-dione | ||
| Canonical SMILES | CCCCOC1=CC=C(C=C1)CC/C([H])=C(S2)/C(N(C2=O)CCN)=O | ||
| Formula | C18H24N2O3S | M.Wt | 348.46 |
| الذوبان | Soluble in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.8698 mL | 14.3488 mL | 28.6977 mL |
| 5 mM | 574 μL | 2.8698 mL | 5.7395 mL |
| 10 mM | 287 μL | 1.4349 mL | 2.8698 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 11 reference(s) in Google Scholar.)