Eltrombopag

Drugbox
IUPAC_name = 3- [(5"E")-5- [1-(3,4-dimethylphenyl)-3-methyl-5-oxo-
2"H"-pyrazol-4-yl] hydrazinylidene] -6-oxo-1-cyclohexa-
1,3-dienyl] benzoic acid

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CAS_number = 496775-61-2
CAS_supplemental = CAS|496775-62-3 (olamine)
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PubChem = 9846180
DrugBank =
C=25 | H=22 | N=4 | O=4
molecular_weight = 442.467 g/mol
smiles = CC1=C(C=C(C=C1)N2C(=O)C(=C(N2)C)NN=C3C=CC=C(C3=O)C4=CC(=CC=C4)C(=O)O)C
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routes_of_administration = Oral

Eltrombopag (rINN, codenamed SB-497115-GR) is a medication under development for conditions that lead to thrombocytopenia (abnormally low platelet counts). It is a small molecule agonist of the c-mpl (TpoR) receptor, which is the physiological target of the hormone thrombopoietin. It is being developed by GlaxoSmithKline and Ligand Pharmaceuticals, [cite web |url=http://www.gsk.com/ControllerServlet?appId=4&pageId=402&newsid=697 |title=GlaxoSmithKline presents rapidly expanding pipeline of oncology and supportive care compounds - GlaxoSmithKline |accessdate=2007-11-29 |format= |work=] and is likely to be marketed in the US as Promacta and in the EU as Revolade. It is currently undergoing regulatory review in the US.

Development

In preclinical studies, the compound was shown to interact selectively with the thrombopoeitin receptor, leading to activation of the JAK-STAT signaling pathway and increased proliferation and differentiation of megakaryocytes. Animal studies confirmed that administration could increase platelet counts. In 73 healthy volunteers, higher doses of eltrombopag caused larger increases in the number of circulating platelets without tolerability problems.cite journal |author=Jenkins JM, Williams D, Deng Y, "et al" |title=Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist |journal=Blood |volume=109 |issue=11 |pages=4739–41 |year=2007 |pmid=17327409 | doi=10.1182/blood-2006-11-057968| url=http://bloodjournal.hematologylibrary.org/cgi/content/full/109/11/4739]

Clinical trials

Eltrombopag has been studied, and shown to be effective, in two major clinical syndromes: idiopathic thrombocytopenic purpura [cite journal|author=Bussel JB, Cheng G, Saleh MN, "et al" |year=2007|title=Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura|journal=N. Engl. J. Med. |volume=357|pages=2237–2247|pmid=18046028|doi=10.1056/NEJMoa073275] and cirrhosis due to hepatitis C (in which low platelet counts may be a contraindication for interferon treatment). [cite journal|author= McHutchison JG, Dusheiko G, Shiffman ML| year=2007|title=Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C|journal=N. Engl. J. Med.|volume=357|pages=2227–2236|pmid=18046027|doi=10.1056/NEJMoa073255]

References