|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
23
|
|
pubmed:dateCreated |
2008-11-13
|
|
pubmed:abstractText |
A potent family of spirocyclic nicotinyl aminobenzamide selective HDAC1/HDAC2 inhibitors (SHI-1:2) is profiled. The incorporation of a biaryl zinc-binding motif into a nicotinyl scaffold resulted in enhanced potency and selectivity versus HDAC3, but also imparted hERG activity. It was discovered that increasing polar surface area about the spirocycle attenuates this liability. Compound 12 induced a 4-fold increase in acetylated histone H2B in an HCT-116 xenograft model study with acute exposure, and inhibited tumor growth in a 21-day efficacy study with qd dosing.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Benzamides,
http://linkedlifedata.com/resource/pubmed/chemical/ERG1 potassium channel,
http://linkedlifedata.com/resource/pubmed/chemical/Ether-A-Go-Go Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases,
http://linkedlifedata.com/resource/pubmed/chemical/Histones,
http://linkedlifedata.com/resource/pubmed/chemical/Niacinamide,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Spiro Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/histone deacetylase 3
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Dec
|
|
pubmed:issn |
1464-3405
|
|
pubmed:author |
pubmed-author:ChenardMelissaM,
pubmed-author:CruzJonathan CJC,
pubmed-author:DahlbergWilliam KWK,
pubmed-author:FlemingJudith CJC,
pubmed-author:HainesBrianB,
pubmed-author:HamblettChristopher LCL,
pubmed-author:HarschAndreasA,
pubmed-author:HughesBethanyB,
pubmed-author:KenificCandia MCM,
pubmed-author:KralAstrid MAM,
pubmed-author:MampreianDawn MDM,
pubmed-author:MethotJoey LJL,
pubmed-author:MiddletonRichard ERE,
pubmed-author:MillerThomas ATA,
pubmed-author:ObiG OGO,
pubmed-author:OzerovaNicoleN,
pubmed-author:SecristJ PaulJP,
pubmed-author:SzewczakAlexander AAA,
pubmed-author:WangHongmeiH
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
1
|
|
pubmed:volume |
18
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
6104-9
|
|
pubmed:dateRevised |
2010-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:18951790-Animals,
pubmed-meshheading:18951790-Antineoplastic Agents,
pubmed-meshheading:18951790-Benzamides,
pubmed-meshheading:18951790-Combinatorial Chemistry Techniques,
pubmed-meshheading:18951790-Ether-A-Go-Go Potassium Channels,
pubmed-meshheading:18951790-HCT116 Cells,
pubmed-meshheading:18951790-Histone Deacetylase Inhibitors,
pubmed-meshheading:18951790-Histone Deacetylases,
pubmed-meshheading:18951790-Histones,
pubmed-meshheading:18951790-Humans,
pubmed-meshheading:18951790-Mice,
pubmed-meshheading:18951790-Mice, Nude,
pubmed-meshheading:18951790-Molecular Structure,
pubmed-meshheading:18951790-Niacinamide,
pubmed-meshheading:18951790-Protein Isoforms,
pubmed-meshheading:18951790-Spiro Compounds,
pubmed-meshheading:18951790-Structure-Activity Relationship,
pubmed-meshheading:18951790-Xenograft Model Antitumor Assays
|
|
pubmed:year |
2008
|
|
pubmed:articleTitle |
SAR profiles of spirocyclic nicotinamide derived selective HDAC1/HDAC2 inhibitors (SHI-1:2).
|
|
pubmed:affiliation |
Department of Drug Design and Optimization, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA. joey_methot@merck.com
|
|
pubmed:publicationType |
Journal Article
|
