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BioAssay: AID 216929

Compound was evaluated for chick Vasoactive intestinal peptide receptor relative competitive induces (relative to alpha, 25-(OH2)-D3)

The C-14 epimers of vitamin D, 14-epi-25-hydroxyvitamin D3 (4) and 14-epi-1 alpha, 25-dihydroxyvitamin D3 (5), were synthesized, and their isomerization via [1,7]-sigmatropic hydrogen shifts to the corresponding previtamin forms (4' and 5', respectively) was studied. The activation parameters of the [1,7]-sigmatropic hydrogen shifts were found to be similar to those of other vitamin D analogues, more ..
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 Tested Compounds
 Tested Compounds
All(5)
 
 
Unspecified(5)
 
 
 Tested Substances
 Tested Substances
All(5)
 
 
Unspecified(5)
 
 
 Related BioAssays
 Related BioAssays
AID: 216929
Data Source: ChEMBL (214256)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-21
Modify Date: 2014-05-19

Data Table ( Complete ):           All
Tested Compounds:
Description:
Title: 14-epi stereoisomers of 25-hydroxy- and 1 alpha,25-dihydroxyvitamin D3: synthesis, isomerization to previtamins, and biological studies.

Abstract: The C-14 epimers of vitamin D, 14-epi-25-hydroxyvitamin D3 (4) and 14-epi-1 alpha, 25-dihydroxyvitamin D3 (5), were synthesized, and their isomerization via [1,7]-sigmatropic hydrogen shifts to the corresponding previtamin forms (4' and 5', respectively) was studied. The activation parameters of the [1,7]-sigmatropic hydrogen shifts were found to be similar to those of other vitamin D analogues, although epimerization at C-14 shifts the equilibrium of the triene chromophore to the previtamin form. The in vivo biological activities of 4, 4', 5, and 5' in the chick in terms of their ability to elicit intestinal calcium absorption and bone calcium mobilization were determined. These vitamin D analogues, the first in the natural steroid series modified at the C-14 position, were essentially devoid of activity. The relative competitive indices (RCIs), derived in an in vitro assay reflecting the ability of these analogues to bind to the chick intestinal nuclear receptor, were determined. Analogues 4, 4', 5, and 5' had RCI values of 0.08, 0.01, 15, and 1.6, respectively, in comparison to the natural ligand, 1 alpha, 25-dihydroxyvitamin D3 (3), whose value is 100 by definition. Thus, the in vivo and in vitro data were somewhat at variance, particularly for 5, which bound significantly to the chick intestinal receptor. In vitro binding studies with the human serum vitamin D binding protein (DBP) were also conducted. The RCI values for human DBP reflects the ability of an analogue to bind to this protein in comparison to the hormone 3, whose value is 100. The measured RCI values for 4, 4', 5, and 5' were 3450, 90, 12, and 2.2, respectively. It is noteworthy that analogue 4 binds approximately 35 times more effectively than the parent hormone 3, but approximately 20 times less effectively than 25-hydroxyvitamin D3 (2).
(PMID: 8057286)
Comment
Putative Target:

ChEMBL Target ID: 12524
Target Type: SINGLE PROTEIN
Pref Name: Vasoactive intestinal peptide receptor
Synonyms: Vasoactive intestinal peptide type I receptor;
Gene Name: VPAC1;
Protein Accession: A5A0U0;
Protein GI: 483508559;
Organism: Gallus gallus
Tax ID: 9031
Target Classification: membrane receptor 7tm2 peptide vasoactive intestinal peptide receptor vasoactive intestinal peptide receptor
Confidence: Homologous single protein target assigned
Relationship Type: Homologous protein target assigned
Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

BAO: Assay Format: biochemical format

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1RCI activity commentRCI activity commentString
2RCI standard flagRCI standard flagInteger
3RCI qualifierRCI qualifierString
4RCI published valueRCI published valueFloat
5RCI standard valueRCI standard valueFloat

Data Table (Concise)
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