| pubmed-article:21090716 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:21090716 | lifeskim:mentions | umls-concept:C0003873 | lld:lifeskim |
| pubmed-article:21090716 | lifeskim:mentions | umls-concept:C0087111 | lld:lifeskim |
| pubmed-article:21090716 | lifeskim:mentions | umls-concept:C0030020 | lld:lifeskim |
| pubmed-article:21090716 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
| pubmed-article:21090716 | lifeskim:mentions | umls-concept:C0143251 | lld:lifeskim |
| pubmed-article:21090716 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
| pubmed-article:21090716 | lifeskim:mentions | umls-concept:C1880355 | lld:lifeskim |
| pubmed-article:21090716 | pubmed:issue | 24 | lld:pubmed |
| pubmed-article:21090716 | pubmed:dateCreated | 2010-12-17 | lld:pubmed |
| pubmed-article:21090716 | pubmed:abstractText | Sphingosine 1-phosphate lyase (S1PL) has been characterized as a novel target for the treatment of autoimmune disorders using genetic and pharmacological methods. Medicinal chemistry efforts targeting S1PL by direct in vivo evaluation of synthetic analogues of 2-acetyl-4(5)-(1(R),2(S),3(R),4-tetrahydroxybutyl)-imidazole (THI, 1) led to the discovery of 2 (LX2931) and 4 (LX2932). The immunological phenotypes observed in S1PL deficient mice were recapitulated by oral administration of 2 or 4. Oral dosing of 2 or 4 yielded a dose-dependent decrease in circulating lymphocyte numbers in multiple species and showed a therapeutic effect in rodent models of rheumatoid arthritis (RA). Phase I clinical trials indicated that 2, the first clinically studied inhibitor of S1PL, produced a dose-dependent and reversible reduction of circulating lymphocytes and was well tolerated at dose levels of up to 180 mg daily. Phase II evaluation of 2 in patients with active rheumatoid arthritis is currently underway. | lld:pubmed |
| pubmed-article:21090716 | pubmed:language | eng | lld:pubmed |
| pubmed-article:21090716 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21090716 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:21090716 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21090716 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21090716 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21090716 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21090716 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21090716 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21090716 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:21090716 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:21090716 | pubmed:issn | 1520-4804 | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:KimballS... | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:OraveczTamasT | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:DongLiL | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:ElyJohnJ | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:ZhangHaimingH | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:HeydornWillia... | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:JessopTheodor... | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:AugeriDavid... | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:WilsonAlanA | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:CarlsenMarian... | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:BagdanoffJeff... | lld:pubmed |
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| pubmed-article:21090716 | pubmed:author | pubmed-author:BrownPhilipP | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:LaiZhongZ | lld:pubmed |
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| pubmed-article:21090716 | pubmed:author | pubmed-author:SonnenburgWil... | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:BednarzMarkM | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:OwusuIris BIB | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:NouraldeenAmr... | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:DonovielMicha... | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:TarverJamesJ | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:HazelwoodJill... | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:LayekSumanS | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:GopinathanSum... | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:MoranLiamL | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:KramerJeffJ | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:MainAlanA | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:AleemSaadatS | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:BotejuLakmalL | lld:pubmed |
| pubmed-article:21090716 | pubmed:author | pubmed-author:FrazierKenny... | lld:pubmed |
| pubmed-article:21090716 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:21090716 | pubmed:day | 23 | lld:pubmed |
| pubmed-article:21090716 | pubmed:volume | 53 | lld:pubmed |
| pubmed-article:21090716 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:21090716 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:21090716 | pubmed:pagination | 8650-62 | lld:pubmed |
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| pubmed-article:21090716 | pubmed:year | 2010 | lld:pubmed |
| pubmed-article:21090716 | pubmed:articleTitle | Inhibition of sphingosine 1-phosphate lyase for the treatment of rheumatoid arthritis: discovery of (E)-1-(4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone oxime (LX2931) and (1R,2S,3R)-1-(2-(isoxazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol (LX2932). | lld:pubmed |
| pubmed-article:21090716 | pubmed:affiliation | Lexicon Pharmaceuticals, Inc., Princeton, New Jersey 08540, USA. | lld:pubmed |
| pubmed-article:21090716 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:21090716 | pubmed:publicationType | Clinical Trial, Phase I | lld:pubmed |
| http://linkedlifedata.com/r... | http://linkedlifedata.com/r... | pubmed-article:21090716 | lld:chembl |
