ICI-199441

Protein target name:

OPRK1

Mechanism of action:

Agonist

Reviewer suggested Concentration for use in cells:

up to 100 nM

Probe Availability

ZINC

Probe Information

Target and Probe Information

Target Details

Target class:

GPCR

Subclass:

Opioid receptors

HUGO ID:

HGNC:8154

Entrez gene ID:

4986

UNIPROT ID:

P41145

Target alias:

K-OR-1, KOR, KOR-1, OPRK, opioid receptor kappa 1

Probe Details

Chemical Probes Portal ID:

CPP1803

Probe alias:

GR-199,441

PubChem CID:

3082718

ChEMBL ID:

CHEMBL38576

SMILES string:

CN([C@H](CN1CCCC1)c2ccccc2)C(=O)Cc3ccc(Cl)c(Cl)c3

InChi Key:

AEJOEPSMZCEYJN-HXUWFJFHSA-N

Orthogonal probe:

Salvinorin A

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

0.04 nM

Potency assay:

[3H]-diprenorphine radioligand inhibitory binding assay [Bioorg. Med. Chem. Lett., (2005) 15:10:2647]. These numbers have been confirmed in multiple publications; additional assays and data are available in CHEMBL.

Structure-activity relationship:

Yes, available in multiple publications (e.g., 15863335, 18487043)

Off target activity

Potency (off target):

Off target protein and potency:

OPRD1: 24 nMOPRM1: 53 nMUTS2R: 4,000 nM

Potency assay (off target):

Measured using [3H]-diprenorphine as radioligand in binding assay (OPRD1, OPRM1) reported in Bioorg. Med. Chem. Lett., (2005) 15:10:2647 and confirmed in subsequent publications. Binding affinity to human urotensin-2 receptor reported in Bioorg. Med. Chem. Lett., (2008) 18:13:3716.

Probe Selectivity in Vitro:

CYP2D6 IC50 = 26 nM

In cell validation

On target activity in cells

Potency in cells:

EC50

0.3 nM

Potency assay (cells):

Agonist activity at human kappa opioid receptor transfected in CHO cells by [35S]GTP-gamma-S binding assay (Bioorg. Med. Chem. Lett., (2008) 18:12:3667). There are additional assay results in ChEMBL.

In vivo validation

Organism:

RatMouse (J Med Chem paper, no PK data published)

Dose:

10 mg/kg

Route of delivery:

Subcutaneous

Other route of delivery:

Intrapaw

Organ of Interest

Organ (O):

CNS, PNS

Target engagement assay:

Formalin flinching (A50 when administered via paw: 0.74 ug; A50 when administered sc: 0.05 mg/kg) and rotarod (ED50 sc=0.14 mg/kg) assays indirecly indicate interaction with target in both CNS and PNS.

Primary Reference

Reference (doi):

10.1016/0014-2999(88)90546-8

Reference (PMID):

15863335 18487043 2850924 8893842 11086731

Endorsed probe

The Chemical Probes Portal endorses this compound as chemical probe for use in cells.

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

3 review(s)

SAB Members

SAB Comments

Opioid agonist signalling is complex and context dependent. This makes probe definitions complicated. This compound is a very potent kappa opioid agonist with opioid receptor subtype selectivity in some contexts. Two extra papers added here demonstrate that at least this compound has been well annotated and compared with other compounds and can thus guide use. One hesitation for calling this a probe is the lack of broad profiling across other targets.

May 19 2020 - 11:18am

Recommended dose for in vivo studies is high when considered in light of the high potency in cell-based assays and the Ki. As a result interpretation of a target specific role in any biological impact of the probe in vivo at this dose should be made with caution and careful consideration of the potential for other targets to contribute to the biological effect.

Nov 16 2020 - 9:20pm

ICI-199441

Probe Availability

Probe Information

Target Details

K-OR-1, KOR, KOR-1, OPRK, opioid receptor kappa 1

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?

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ICI-199441

Probe Availability

Probe Information

Target Details

K-OR-1, KOR, KOR-1, OPRK, opioid receptor kappa 1

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?