Eltrombopag (SB-497115) 是一种具有口服活性的thrombopoietin-receptor非肽激动剂。Eltrombopag 可促血小板的活性，用于治疗血小板计数低的慢性免疫性血小板减少症。Eltrombopag 可用于心血管的研究。Eltrombopag 对多药耐药的金黄色葡萄球菌 (Staphylococcus aureus) 也有很强的抑制作用。Eltrombopag 还可诱导肝癌细胞凋亡 (apoptosis)。
| 生物活性 | Eltrombopag (SB-497115) is an orally activethrombopoietin receptornonpeptide agonist. Eltrombopag owns thrombopoietic activity, and has been used to research low blood platelet counts with chronic immune thrombocytopenia. Eltrombopag can be used for the research of cardiovascular. Eltrombopag also has highly inhibitory effects against multidrug resistantStaphylococcus aureus. Eltrombopag can induceapoptosisin hepatocellular carcinomab (HCC) as well[1][2][3][4][5]. |
| IC50& Target | Thrombopoietin Receptor,Staphylococcus aureus, Apoptosis[1][3][5] |
体外研究
(In Vitro) | Eltrombopag (0.002-50 μM; 4 h) possesses activity in murine BAF3 cells transfected with the luciferase reporter gene[1].Eltrombopag (30 μM; 120 min) affects the activates of p-STAT5 in N2C-Tpo cells[1].Eltrombopag (30 μM; 120 min) activates p-STAT5 in megakaryocytes[1].Eltrombopag (0.1 nM-10 μM; 30 min) stimulates proliferation of BAF3/hTpoR cells[1].Eltrombopag (0.03-3 μM; 10 days) increases the differentiation of bone marrow CD34+cells into CD41+megakaryocytes[1].Eltrombopag (0-3 μM; 72 h) affects N2C-Tpo cell apoptosis[1].
Eltrombopag efficiently inhibitsPneumococcalgrowth with MIC50of 0.3 mg/L, but shows no activity against Gram-negative bacteria[3].
Eltrombopag (0-200 mg/L; 24 h; Caco-2 and HepG2 cells) inhibitsStaphylococcus aureusgrowth with an MIC50of 1.5 mg/L, and exhibits higher potency when co-treats withVancomycin(HY-B0671) with an MIC50of 1.2 mg/L[3].
Eltrombopag (0 or 10 μg/mL; 72 h) significantly induces G0/G1 phase arrest in Huh7 cells[5].
Eltrombopag (0.1-100 μg/mL; 72 h) exhibits anti-proliferative activity against HCC cell lines[5].
Cell Viability Assay[1] | Cell Line: | Murine BAF3 cells | | Concentration: | 0.002-50 μM | | Incubation Time: | 4 h | | Result: | Effectively inhibited murine BAF3 cells with human TpoR with an EC50value of 0.27 μM. |
[1][1] | Cell Line: | N2C-Tpo cells and CD34+ | | Concentration: | 30 μM for N2C-Tpo cells; 0, 1, 3 and 10 μM for CD34+ | | Incubation Time: | 120 min for N2C-Tpo cells; 30 min for CD34+ | | Result: | Activated phospho-STAT5 and maximum signal intensity exhibited at 60 minutes after treatment in N2C-Tpo cells.
Dose-dependently activated STAT5 phosphorylation at 30 minutes after treatment in CD34+. |
Cell Proliferation Assay[1] | Cell Line: | BAF3/hTpoR cells | | Concentration: | 0.1 nM-10 μM | | Incubation Time: | 2 days | | Result: | Promoted BAF3/hTpoR cells proliferation after incubated for 2 days with an EC50of 0.03 μM. |
Cell Differentiation Assay[1] | Cell Line: | CD34+ | | Concentration: | 0.003, 0.01, 0.03, 0.1, 0.3, 1 and 3 μM | | Incubation Time: | 10 days | | Result: | Dose-dependently stimulated the differentiation from bone marrow CD34+cells to CD41+megakaryocytes with an EC50value of 0.1 μM. |
Apoptosis Analysis[1] | Cell Line: | N2C-Tpo cells | | Concentration: | 0, 0.003, 0.01, 0.03, 0.1, 0.3, 1 and 3 μM | | Incubation Time: | 72 hours | | Result: | Exhibited dose-dependently antiapoptotic effects N2C-Tpo cells with a concentration over 0.03 μM. |
Cell Proliferation Assay[5] | Cell Line: | Huh7, HepG2 and Hep3B cells (preloaded with iron (500 μg/ml FAC) for 24 h) | | Concentration: | 0.1-100 μg/mL | | Incubation Time: | 72 h | | Result: | Exhibited anti-proliferative activity against HCC cell lines with IC50s of 5.7 μg/ml for Huh7, 5.4 μg/ml for HepG2, and 4.7 μg/ml for Hep3B. |
Cell Cycle Analysis[5] | Cell Line: | Huh7 cells | | Concentration: | 0 or 10 μg/mL | | Incubation Time: | 72 h | | Result: | Significantly induced G0/G1 phase arrest. |
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体内研究
(In Vivo) | Eltrombopag Olamine (10 mg/kg; p.o. once a day for 5 days) shows good tolerance in chimpanzees[1].
Eltrombopag Olamine (17.6 mg/kg; i.p.; once a day for 2 days) significantly reduces meanS. aureuscounts in mice nasal infection[3].
| Animal Model: | Female chimpanzees[1] | | Dosage: | 10 mg/kg | | Administration: | Oral gavage; 10 mg/kg once a day; for 5 days | | Result: | Appeared a goes up and then goes back tendency of platelet counts after treatment, and showed no bad effects of hematology, coagulation, or clinical chemistry parameters on animal. |
| Animal Model: | C57BL/6 male mice (7 weeks, 20-22 g; injectedS. aureus(5 × 108CFU suspended in 40 μL PBS) into the nasal cavities)[3] | | Dosage: | 17.6 mg/kg | | Administration: | IP; once a day for 2 days | | Result: | Significantly reduced mean bacterial counts (5.0 × 106CFU/lung) in the nasal infection model compared with control PBS (5.2 × 107CFU/lung) mice. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 8.33 mg/mL(18.83 mM;Need ultrasonic) H2O :< 0.1 mg/mL(insoluble) 配制储备液 | 1 mM | 2.2600 mL | 11.3002 mL | 22.6004 mL | | 5 mM | 0.4520 mL | 2.2600 mL | 4.5201 mL | | 10 mM | 0.2260 mL | 1.1300 mL | 2.2600 mL |
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