K145 hydrochloride
(Synonyms: 3-(2-氨基乙基)-5-[3-(4-丁氧基苯基)亚丙基]-2,4-噻唑烷二酮盐酸盐) 目录号 : GC36372
K145 hydrochloride是一种选择性鞘磷酸酶2（SphK2）抑制剂，IC50值为4.3μM，Ki值为6.4µM，具有抗癌活性。
Cas No.:1449240-68-9
Sample solution is provided at 25 µL, 10mM.
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K145 hydrochloride 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 hydrochloride inhibits SphK2 activity by competitively binding to it, without affecting the homologous enzyme SphK1[3]. K145 hydrochloride 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 hydrochloride (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 hydrochloride (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 hydrochloride (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 hydrochloride) 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 hydrochloride, 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 hydrochloride 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.
K145 hydrochloride是一种选择性鞘磷酸酶2（SphK2）抑制剂，IC50值为4.3μM，Ki值为6.4µM，具有抗癌活性[1, 2]。K145 hydrochloride通过竞争性结合SphK2抑制其活性，对同源酶SphK1无影响[3]。K145 hydrochloride能够抑制单体浆细胞瘤（SP）细胞的生长[4]。
在体外，K145 hydrochloride（2µM）预处理乳腺癌细胞（MCF-7、MDA-MB-231、LM2-4细胞），均显著抑制了表皮生长因子（EGF）介导的细胞迁移，显著降低了LM2-4细胞内鞘氨醇-1-磷酸（S1P）水平[5]。
在体内，K145 hydrochloride（5, 10mg/kg）通过腹腔注射治疗ob/ob小鼠和db/db小鼠10天，减轻了db/db小鼠的肝脏脂质蓄积并降低了其空腹血糖水平，调节了ob/ob小鼠肝脏中脂质代谢相关基因的mRNA水平[6]。K145 hydrochloride（50mg/kg/day）通过腹腔注射治疗胶质母细胞瘤（GBM）细胞异种移植小鼠30天，减缓了肿瘤生长速度，提高了小鼠生存率[7]。
| 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 hydrochloride (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 hydrochloride 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 hydrochloride 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 hydrochloride ameliorated fatty liver of ob/ob mice. K145 hydrochloride ameliorated hepatic lipid accumulation and fasting blood glucose of db/db mice. Hepatic mRNA levels for Lipid metabolism related genes were regulated by K145 hydrochloride treatment of ob/ob mice. |
References: | |
| Cas No. | 1449240-68-9 | SDF | |
| 别名 | 3-(2-氨基乙基)-5-[3-(4-丁氧基苯基)亚丙基]-2,4-噻唑烷二酮盐酸盐 | ||
| Canonical SMILES | O=C(N(CCN)C/1=O)SC1=C/CCC2=CC=C(OCCCC)C=C2.[H]Cl | ||
| 分子式 | C18H25ClN2O3S | 分子量 | 384.92 |
| 溶解度 | Water: 126.7 mg/mL (329.16 mM and warming); DMSO: 50 mg/mL (129.90 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5979 mL | 12.9897 mL | 25.9794 mL |
| 5 mM | 519.6 μL | 2.5979 mL | 5.1959 mL |
| 10 mM | 259.8 μL | 1.299 mL | 2.5979 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
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Quality Control & SDS
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- Purity: >98.00%
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