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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
19
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pubmed:dateCreated |
2008-9-23
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pubmed:abstractText |
The lead optimization of a novel series of benzo[a]carbazole-based small molecule agonists of the thrombopoietin (Tpo) receptor is reported. The chemical instability of the dihydro-benzo[a]carbazole lead 2 was successfully addressed in the design and evaluation of compounds which also demonstrated improved potency compared to 2. Members of the scaffold have been identified which are full agonists that demonstrate cellular functional potency <50 nM. Analog 21 demonstrates equivalent efficacy in the human megakaryocyte differentiation (CFU-mega) assay compared to Eltrombopag.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1464-3405
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pubmed:author |
pubmed-author:AlperPhil BPB,
pubmed-author:ChowDonaldD,
pubmed-author:GerkenAndreaA,
pubmed-author:HeYunY,
pubmed-author:KaranewskyDonald SDS,
pubmed-author:KimMin-JuMJ,
pubmed-author:LaoJianminJ,
pubmed-author:LuWenshuoW,
pubmed-author:MarsiljeThomas HTH,
pubmed-author:MichellysPierre-YvesPY,
pubmed-author:MutnickDanielD,
pubmed-author:SeidelH MartinHM,
pubmed-author:TianShin-ShaySS
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5259-62
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pubmed:meshHeading |
pubmed-meshheading:18783949-Benzene Derivatives,
pubmed-meshheading:18783949-Carbazoles,
pubmed-meshheading:18783949-Combinatorial Chemistry Techniques,
pubmed-meshheading:18783949-Drug Design,
pubmed-meshheading:18783949-Humans,
pubmed-meshheading:18783949-Inhibitory Concentration 50,
pubmed-meshheading:18783949-Megakaryocytes,
pubmed-meshheading:18783949-Molecular Structure,
pubmed-meshheading:18783949-Nuclear Magnetic Resonance, Biomolecular,
pubmed-meshheading:18783949-Receptors, Thrombopoietin,
pubmed-meshheading:18783949-Structure-Activity Relationship,
pubmed-meshheading:18783949-Thrombopoietin
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pubmed:year |
2008
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pubmed:articleTitle |
Optimization of small molecule agonists of the thrombopoietin (Tpo) receptor derived from a benzo[a]carbazole hit scaffold.
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pubmed:affiliation |
Genomics Institute of the Novartis Research Foundation (GNF), San Diego, CA 92121, USA. TMarsilje@gnf.org
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pubmed:publicationType |
Journal Article
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