Eltrombopag

SKU: orb1224942

Description

Eltrombopag is an orally active thrombopoietin receptor agonist with megakaryopoiesis stimulating activity. Eltrombopag binds to and stimulates the platelet thrombopoietin receptor (TPO-R or CD110), a member of the hematopoietin receptor superfamily. Activation of TPO-R leads to the proliferation and differentiation of megakaryocytes, thereby increasing the production of blood platelets.(In Vitro):Eltrombopag (0.002-50 μM; 4 h) possesses activity in murine BAF3 cells transfected with the luciferase reporter gene.Eltrombopag (30 μM; 120 min) affects the activates of p-STAT5 in N2C-Tpo cells.Eltrombopag (30 μM; 120 min) activates p-STAT5 in megakaryocytes.Eltrombopag (0.1 nM-10 μM; 30 min) stimulates proliferation of BAF3/hTpoR cells.Eltrombopag (0.03-3 μM; 10 days) increases the differentiation of bone marrow CD34+ cells into CD41+ megakaryocytes.Eltrombopag (0-3 μM; 72 h) affects N2C-Tpo cell apoptosis.Eltrombopag efficiently inhibits Pneumococcal growth with MIC50 of 0.3 mg/L, but shows no activity against Gram-negative bacteria.Eltrombopag (0-200 mg/L; 24 h; Caco-2 and HepG2 cells) inhibits Staphylococcus aureus growth with an MIC50 of 1.5 mg/L, and exhibits higher potency when co-treats with Vancomycin (HY-B0671) with an MIC50 of 1.2 mg/L.Eltrombopag (0 or 10 μg/mL; 72 h) significantly induces G0/G1 phase arrest in Huh7 cells.Eltrombopag (0.1-100 μg/mL; 72 h) exhibits anti-proliferative activity against HCC cell lines.(In Vivo):Eltrombopag Olamine (10 mg/kg; p.o. once a day for 5 days) shows good tolerance in chimpanzees.Eltrombopag Olamine (17.6 mg/kg; i.p.; once a day for 2 days) significantly reduces mean S. aureus counts in mice nasal infection.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 496775-61-2
• MW: 442.47
• Purity: >98% (HPLC)
• Formula: C₂₅H₂₂N₄O₄
• SMILES: CC1=C(C=C(C=C1)N2C(=O)C(=C(N2)C)N/N=C/3\C=CC=C(C3=O)C4=CC(=CC=C4)C(=O)O)C
• Target: Thrombin
• Solubility: DMSO: 26 mg/mL warmed (58.76 mM)

Bioactivity

• In Vivo:
  Animal model: Female chimpanzees. 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; injected S. aureus (5 × 108 CFU suspended in 40 μL PBS) into the nasal cavities). Dosage: 17.6 mg/kg. Administration: IP; once a day for 2 days. Result: Significantly reduced mean bacterial counts (5.0 × 106 CFU/lung) in the nasal infection model compared with control PBS (5.2 × 107 CFU/lung) mice.
• In Vitro:
  Cell Viability Assay 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 EC50 value of 0.27 μM. 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 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 EC50 of 0.03 μM. Cell Differentiation Assay 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 EC50 value of 0.1 μM. Apoptosis Analysis 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 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 Cell line: Huh7 cells. Concentration: 0 or 10 μg/mL. Incubation time: 72 h. Result: Significantly induced G0/G1 phase arrest.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

SB 497115

Quick Database Links

Gene Symbol

Thrombin