Linked Life Data

10390605

Source:http://linkedlifedata.com/resource/pubmed/id/10390605

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1999-10-12
pubmed:abstractText
Mycophenolic acid (MPA) is the most potent and specific inhibitor of inosine monophosphate dehydrogenase (IMPDH). This compound was reported to bind the NAD site of IMPDH and mimic the binding of nicotinamide moiety of nicotinamide adenine dicnucleotide. We linked MPA derivatives with the adenine moiety of NAD through a methylenebis(phonphonate) birdge to form novel mycophenolic adenine dinucleotides (MADs) which resemble well the intact natural cofactor. The MAD analogues differ by the length of the side chain (linker) between the aromatic ring of mycophenolic derivative and the beta-phosphorus atom of the adenosine bis(phosphonate) moiety. Regardless of the linker size, MADs were found to be potent inhibitors of human IMPDH type I and type II with Ki's = 0.25-0.52 microM, an order of magnitude less potent than MPA itself (Ki = 0.01-0.04 microM). The growth of K562 cells was inhibited by MPA (IC50 = 0.03 microM) and the MAD analogues (IC50 = 0.01-1.15 microM) with a similar potency. Accordingly, a suppression of alloantigen- induced proliferation of human lymphocytes by the MAD analogues at concentration of 10-20 microM was equally effective as that observed for MPA. In contrast to MPA, MAD analogues were found to be resistant to glucuronidation in vitro. Since therapeutic potential of MPA is limited by its undesirable glucuronidation, the glucuronidation- resistant MAD analogues may be superior immunosuppressants if they are not glucuronidated in vivo.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0929-8673
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
629-34
pubmed:dateRevised
2008-4-5
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Novel mycophenolic adenine bis(phosphonate)s as potential immunosuppressants.
pubmed:affiliation
Pharmasset, Inc., 1860 Montreal Road, Atlanta, GA 30084, USA.
pubmed:publicationType
Journal Article