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BioAssay: AID 613495

Partial agonist activity at recombinant human vasopressin V2 receptor expressed in HEK293 cells by luciferase reporter gene assay

[Arg(8)]vasopressin (AVP) produces vasoconstriction via V(1a) receptor (V(1a)R)-mediated vascular smooth muscle cell contraction and is being used to increase blood pressure in septic shock, a form of vasodilatory hypotension. However, AVP also induces V(2) receptor (V(2)R)-mediated antidiuresis, vasodilation, and coagulation factor release, all deleterious in septic shock. The V(1a)R agonist more ..
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 Tested Compounds
 Tested Compounds
All(11)
 
 
Unspecified(11)
 
 
 Tested Substances
 Tested Substances
All(11)
 
 
Unspecified(11)
 
 
 Related BioAssays
 Related BioAssays
AID: 613495
Data Source: ChEMBL (763506)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-04-30
Modify Date: 2013-11-17

Data Table ( Complete ):           All
Target
Sequence: RecName: Full=Vasopressin V2 receptor; Short=V2R; AltName: Full=AVPR V2; AltName: Full=Antidiuretic hormone receptor; AltName: Full=Renal-type arginine vasopressin receptor
Description ..   
Comment ..   

Gene:AVPR2     Conserved Domain     Related Protein 3D Structures     More BioActivity Data..
Tested Compounds:
Description:
Title: New, potent, selective, and short-acting peptidic V1a receptor agonists.

Abstract: [Arg(8)]vasopressin (AVP) produces vasoconstriction via V(1a) receptor (V(1a)R)-mediated vascular smooth muscle cell contraction and is being used to increase blood pressure in septic shock, a form of vasodilatory hypotension. However, AVP also induces V(2) receptor (V(2)R)-mediated antidiuresis, vasodilation, and coagulation factor release, all deleterious in septic shock. The V(1a)R agonist terlipressin (H-Gly(3)[Lys(8)]VP) also lacks selectivity vs the V(2)R and has sizably longer duration of action than AVP, preventing rapid titration of its vasopressor effect in the clinic. We designed and synthesized new short acting V(1a)R selective analogues of general structure [Xaa(2),Ile(3),Yaa(4),Zaa(8)]VP. The most potent and selective compounds in in vitro functional assays (e.g., [Phe(2),Ile(3),Asn(Me(2))(4),Orn(8)]VP (31), [Phe(2),Ile(3),Asn((CH(2))(3)OH)(4),Orn(8)]VP (34), [Phe(2),Ile(3),Hgn(4),Orn(iPr)(8)]VP (45), [Phe(2),Ile(3),Asn(Et)(4),Dab(8)]VP (49), [Thi(2),Ile(3),Orn(iPr)(8)]VP (59), [Cha(2),Ile(3),Asn(4),Orn(iPr)(8)]VP (68)) were tested by intravenous bolus in rats for duration of vasopressive action. Analogues 31, 34, 45, and 49 were as short-acting as AVP. Compound 45, FE 202158, is currently undergoing clinical trials in septic shock.
(PMID: 21688787)
Categorized Comment
ChEMBL Assay Type: Functional

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Assay Cell Type: HEK293

ChEMBL Target ID: 112

ChEMBL Target Type: Target is a single protein chain

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Efficacy activity commentEfficacy activity commentString
2Efficacy standard flagEfficacy standard flagInteger
3Efficacy qualifierEfficacy qualifierString
4Efficacy published valueEfficacy published valueFloat%
5Efficacy standard valueEfficacy standard valueFloat%

Data Table (Concise)
Classification
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