When luciferase reporter gene is transfected into mouse BAF3 cells, eltrombopag (0.002-50 μM; 4 h) exhibits activity [1]. Eltrombopag (30 μM; 120 min) has an impact on the way that p-N2C-Tpo STAT5 is activated in cells [1]. In megakaryocytes, eltrombopag (30 μM; 120 minutes) stimulates p-STAT5[1]. BAF3/hTpoR cell proliferation is stimulated by eltrombopag (0.1 nM-10 μM; 30 min) [1]. Eltrombopag (0.03-3 μM; 10 days) promotes CD34+ cells in the bone marrow to differentiate into CD41+ megakaryocytes [1]. N2C-Tpo cell apoptosis is impacted by eltrombopag (0-3 μM; 72 h)[1]. With a MIC50 of 0.3 mg/L, eltrombopag efficiently prevents the growth of pneumococci, but it is ineffective against Gram-negative bacteria [3]. Eltrombopag (0 -200 mg/L; 24 hours; HepG2 and Caco-2 cells) has a MIC50 of 1.5 mg/L, which is less effective than that of vancomycin (MIC50 of 1.2 mg/L), when used in combination. L[3]. In Huh7 cells, eltrombopag (0 or 10 μg/mL; 72 h) strongly promotes G0/G1 phase arrest [5]. On HCC cell lines, eltrombopag (0.1-100 μg/mL; 72 h) exhibits anti-proliferative action [5].

Chimpanzees can tolerate Eltrombopag Olamine (10 mg/kg) when given orally once day for five days [1]. Mean S is greatly decreased by elotrombopag Olamine (17.6 mg/kg; i.p.; once daily for two days). Mice's nasal infections with aureus numbers [3].

Cell Viability Assay[1]
Cell Types: Murine BAF3 cells
Tested Concentrations: 0.002-50 μM
Incubation Duration: 4 h
Experimental Results: Effectively inhibited murine BAF3 cells with human TpoR with an EC50 value of 0.27 μM. [1][1]
Cell Types: N2C-Tpo cells and CD34+
Tested Concentrations: 30 μM for N2C-Tpo cells; 0, 1, 3 and 10 μM for CD34+
Incubation Duration: 120 min for N2C-Tpo cells; 30 min for CD34+
Experimental Results: Activated phospho-STAT5 and maximum signal intensity demonstrated at 60 minutes after treatment in N2C-Tpo cells. Dose-dependently activated STAT5 phosphorylation at 30 minutes after treatment in CD34+.

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Cell Proliferation Assay[1]
Cell Types: BAF3/hTpoR cells
Tested Concentrations: 0.1 nM-10 μM
Incubation Duration: 2 days
Experimental Results: Promoted BAF3/hTpoR cells proliferation after incubated for 2 days with an EC50 of 0.03 μM.

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Cell Differentiation Assay[1]
Cell Types: CD34+
Tested Concentrations: 0.003, 0.01, 0.03, 0.1, 0.3, 1 and 3 μM
Incubation Duration: 10 days
Experimental Results: Dose-dependently stimulated the differentiation from bone marrow CD34+ cells to CD

Animal/Disease Models: Female chimpanzees[1]
Doses: 10 mg/kg
Route of Administration: po (oral gavage); 10 mg/kg one time/day; for 5 days
Experimental Results: Appeared a goes up and then goes back tendency of platelet counts after treatment, and demonstrated no bad effects of hematology, coagulation, or clinical chemistry parameters on animal.

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Animal/Disease Models: C57BL/6 male mice (7 weeks, 20-22 g; injected S. aureus (5 × 108 CFU suspended in 40 µL PBS) into the nasal cavities )[3]
Doses: 17.6 mg/kg
Route of Administration: IP; one time/day for 2 days
Experimental Results: Dramatically decreased mean bacterial counts (5.0 × 106 CFU/lung) in the nasal infection model compared with control PBS (5.2 × 107 CFU/lung) lung) mice.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Minimal information is available on the use of eltrombopag during breastfeeding. One breastfed infant with thrombocytosis at birth that was possibly prolonged by eltrombopag in milk. Until more data become available, romiplostim should be used with careful infant monitoring of infant blood parameters during breastfeeding, especially while nursing a newborn or preterm infant. The manufacturer recommends avoiding breastfeeding during the use of eltrombopag. Based on the drug’s half-life, the drug should be eliminated by the mother 8 days after the last dose.
◉ Effects in Breastfed Infants
An infant was born to a mother taking eltrombopag in a maximum dose of 100 mg during pregnancy. At birth, the infant had thrombocytosis, which persisted for a few weeks while the mother was breastfeeding. The extent of breastfeeding and the maternal dose were not stated. The authors felt that the persistence of thrombocytosis in the infant was possibly caused by eltrombopag in milk.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

[1]. Erickson-Miller CL, et al. Preclinical activity of eltrombopag (SB-497115), an oral, nonpeptide thrombopoietin receptor agonist. Stem Cells. 2009 Feb;27(2):424-30.
[2]. Erickson-Miller CL, et al. Discovery and characterization of a selective, nonpeptidyl thrombopoietin receptor agonist. Exp Hematol. 2005 Jan;33(1):85-93.
[3]. Lee H, et al. Repurposing Eltrombopag for Multidrug Resistant Staphylococcus aureus Infections. Antibiotics (Basel). 2021 Nov 9;10(11):1372.
[4]. Juan Zhu, et al. Identification of Eltrombopag as a Repurposing Drug Against Staphylococcus epidermidis and its Biofilms. Curr Microbiol. 2021 Feb 21.
[5]. Kurokawa T, et al. The Eltrombopag antitumor effect on hepatocellular carcinoma. Int J Oncol. 2015 Nov;47(5):1696-702.

Eltrombopag is a hydrazine in which each nitrogen atom is substituted, one by a 3'-carboxy-2-hydroxy[1,1'-biphenyl]-3-yl group and the other by a 1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene group. A small molecule agonist of the c-mpl (TpoR) receptor (the physiological target of the hormone thrombopoietin), it has been developed as a medication for conditions that lead to thrombocytopenia (abnormally low platelet counts). It has a role as a thrombopoietin receptor agonist and a xenobiotic. It is a member of hydrazines, a member of pyrazoles and a member of benzoic acids.
Eltrombopag is a Thrombopoietin Receptor Agonist. The mechanism of action of eltrombopag is as a Thrombopoietin Receptor Agonist, and Organic Anion Transporting Polypeptide 1B1 Inhibitor, and Breast Cancer Resistance Protein Inhibitor, and UGT1A1 Inhibitor, and UGT1A3 Inhibitor, and UGT1A4 Inhibitor, and UGT1A6 Inhibitor, and UGT1A9 Inhibitor, and UGT2B7 Inhibitor, and UGT2B15 Inhibitor. The physiologic effect of eltrombopag is by means of Increased Megakaryocyte Maturation, and Increased Platelet Production.
See also: Romiplostim (annotation moved to); Eltrombopag (annotation moved to).

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Drug Indication
Revolade is indicated for the treatment of adult patients with primary immune thrombocytopenia (ITP) who are refractory to other treatments (e. g. corticosteroids, immunoglobulins) (see sections 4. 2 and 5. 1). Revolade is indicated for the treatment of paediatric patients aged 1 year and above with primary immune thrombocytopenia (ITP) lasting 6 months or longer from diagnosis and who are refractory to other treatments (e. g. corticosteroids, immunoglobulins) (see sections 4. 2 and 5. 1). Revolade is indicated in adult patients with chronic hepatitis C virus (HCV) infection for the treatment of thrombocytopenia, where the degree of thrombocytopenia is the main factor preventing the initiation or limiting the ability to maintain optimal interferon-based therapy (see sections 4. 4 and 5. 1). Revolade is indicated in adult patients with acquired severe aplastic anaemia (SAA) who were either refractory to prior immunosuppressive therapy or heavily pretreated and are unsuitable for haematopoietic stem cell transplantation (see section 5. 1).

C25H22N4O4

442.47

442.164

496775-61-2

Eltrombopag Olamine;496775-62-3;(E/Z)-Eltrombopag-13C4;1217230-31-3

135449332

Typically exists as solid at room temperature

1.3±0.1 g/cm3

656.8±65.0 °C at 760 mmHg

242-244ºC

351.0±34.3 °C

0.0±2.1 mmHg at 25°C

1.667

3.7

3

7

5

33

812

0

O=C1C(=C(C([H])([H])[H])N([H])N1C1C([H])=C([H])C(C([H])([H])[H])=C(C([H])([H])[H])C=1[H])/N=N/C1=C([H])C([H])=C([H])C(=C1O[H])C1C([H])=C([H])C([H])=C(C(=O)O[H])C=1[H]

SVOQIEJWJCQGDQ-UHFFFAOYSA-N

InChI=1S/C25H22N4O4/c1-14-10-11-19(12-15(14)2)29-24(31)22(16(3)28-29)27-26-21-9-5-8-20(23(21)30)17-6-4-7-18(13-17)25(32)33/h4-13,28,30H,1-3H3,(H,32,33)

3-[2-[(2Z)-1-(3,4-Dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-ylidene]hydrazinyl]-2-hydroxy-[1,1-biphenyl]-3-carboxylic acid

Eltrombopag; SB497115; SB-497115; SB 497115; SB497115GR; trade name: PROMACTA

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 1 mg/mL (2.26 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 + to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)