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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 |
1998-10-8
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pubmed:abstractText |
A new series of GH secretagogues derived from ipamorelin is described. In an attempt to obtain oral bioavailability, by reducing the size and the number of potential hydrogen-bonding sites of the compounds, a strategy using the peptidomimetic fragment 3-(aminomethyl)benzoic acid and sequential backbone N-methylations was applied. Several compounds from this series release GH with high in vitro potency and efficacy in a rat pituitary cell assay and high in vivo potency and efficacy in anesthetized rats. The tetrapeptide NNC 26-0235 (3-(aminomethyl)benzoyl-D-2Nal-N-Me-D-Phe-Lys-NH2) shows, following iv administration, comparable in vivo potency to ipamorelin, GHRP-2, and GHRP-6 with an ED50 in swine at 2 nmol/kg. NNC 26-0235 demonstrated a 10% oral bioavailability in dogs, and NNC 26-0235 and ipamorelin were able to increase basal GH level by more than 10-fold after oral administration of a dose of 1.8 and 2.7 mg/kg, respectively. The tripeptide NNC 26-0323 (3-(aminomethyl)benzoic acid-N-Me-D-2Nal-N-Me-D-Phe-ol) which showed moderate in vitro potency but lacked in vivo potency demonstrated a 20% oral bioavailability in rats.
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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 |
Sep
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:AndersenP HPH,
pubmed-author:AnkersenMM,
pubmed-author:HansenB SBS,
pubmed-author:HansenT KTK,
pubmed-author:JohansenN LNL,
pubmed-author:LawHH,
pubmed-author:LundtB FBF,
pubmed-author:MadsenKK,
pubmed-author:NielsenK KKK,
pubmed-author:PeschkeBB,
pubmed-author:RauhAA,
pubmed-author:ThogersenHH
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
41
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3699-704
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9733495-Administration, Oral,
pubmed-meshheading:9733495-Animals,
pubmed-meshheading:9733495-Biological Availability,
pubmed-meshheading:9733495-Dogs,
pubmed-meshheading:9733495-Female,
pubmed-meshheading:9733495-Growth Hormone,
pubmed-meshheading:9733495-Hormones,
pubmed-meshheading:9733495-Injections, Intravenous,
pubmed-meshheading:9733495-Magnetic Resonance Spectroscopy,
pubmed-meshheading:9733495-Male,
pubmed-meshheading:9733495-Molecular Mimicry,
pubmed-meshheading:9733495-Oligopeptides,
pubmed-meshheading:9733495-Pituitary Gland,
pubmed-meshheading:9733495-Rats,
pubmed-meshheading:9733495-Rats, Sprague-Dawley,
pubmed-meshheading:9733495-Structure-Activity Relationship,
pubmed-meshheading:9733495-Swine
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pubmed:year |
1998
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pubmed:articleTitle |
A new series of highly potent growth hormone-releasing peptides derived from ipamorelin.
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pubmed:affiliation |
Departments of Medicinal Chemistry Research, Assay and Cell Technology, Growth Hormone Pharmacology, Health Care Discovery and Preclinical Development, Novo Nordisk Park, DK-2760 Måløv, Denmark. miak@novo.dk
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pubmed:publicationType |
Journal Article,
In Vitro
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