(R)-Zinc-3573

Protein target name:

MRGPRX2

Mechanism of action:

Agonist

Recommended Concentration for use in cells:

up to 1 uM

Probe Availability

TOCRIS

Probe Information

Target and Probe Information

Target Details

Target class:

GPCR

Subclass:

Mast cell-specific receptor

HUGO ID:

HGNC:17983

Entrez gene ID:

117194

UNIPROT ID:

Q96LB1

Target alias:

MGRG3, MRGX2

Probe Details

Chemical Probes Portal ID:

CPP1847

Probe alias:

ZINC72453573, R-zinc-3573, zinc-3573

PubChem CID:

95882507

ChEMBL ID:

CHEMBL4520293

SMILES string:

CN(C)[C@@H]1CCN(C1)C2=CC(=NC3=CC=NN32)C4=CC=CC=C4

InChi Key:

XKBSPAZCFAIBJL-OAHLLOKOSA-N

Control compound:

ZINC72453574

Physico-chemical properties

NMR:

1H NMR (600 MHz, CDCl3) δ 8.05 – 7.97 (m, 2H), 7.95 (d, J = 2.3 Hz, 1H), 7.52 – 7.39 (m, 3H), 6.48 (d, J = 2.3 Hz, 1H), 6.12 (s, 1H), 4.30 (t, J = 8.8 Hz, 1H), 4.23 (t, J = 9.8 Hz, 1H), 4.02 (q, J = 9.3 Hz, 1H), 3.83 (t, J = 9.5 Hz, 1H), 2.91 – 2.81 (m, 1H), 2.36 (s, 6H), 2.30 – 2.21 (m, 1H), 2.02 – 1.91 (m, 1H).

13C NMR (151 MHz, CDCl3) δ 157.5, 151.8, 147.9, 143.8, 139.2, 129.6, 128.7 (2C), 127.3 (2C), 94.9, 86.2, 65.2, 55.0, 50.1, 44.5 (2C), 30.1.

Validation in Cells and Model Organisms

In cell validation

On target activity in cells

Potency in cells:

EC50

760nM and 1000nM

Potency assay (cells):

PRESTO-Tango arrestin recruitment, FLIPR calcium assay

Off target activity in cells

Probe Selectivity in Cell:

315 GPCRs were screened at 10uM. Potential hits were re-screened by dose response. Two off-targets were identified: DRD4,EC50 >10uM; GPR37, EC50 >10uM

Primary Reference

Reference (doi):

10.1038/nchembio.2334 10.1038/nchembio.2490 10.1038/nrd.2017.77

Reference (PMID):

28288109 29045379 28417990

Under Review

This probe is in the process of SAB review. Please continue to check back for new reviews and commentary.

SAB Rating

Rating for use in Cells

2 review(s)

Rating for use in Model Organisms

2 review(s)

SAB Members

SAB Comments

This probe was identified through an innovative approach to first screen a set of compounds using PRESTO-Tango, then using these results to refine a structural model that could be used for subsequent docking studies with a large set of compounds. These efforts have led to a probe is quite structurally novel relative to other GPCR ligands, has extremely high selectivity against a large collection of GPCRs as well as a broad panel of 76 kinases, and is active in an orthogonal cell assay. Another key attribute is that it possesses an inactive enantiomer, which can be used as an inactive probe. The deficiencies of the probe are its relatively modest cellular functional potency (740 nM), the lack of a binding data (Kd) to the receptor, and lack of ADME/PK data to guide in vivo use.

May 15 2020 - 1:52pm

(R)-Zinc-3573

Probe Availability

Probe Information

Target Details

MGRG3, MRGX2

Probe Details

Physico-chemical properties

In cell validation

Primary Reference

Supporting Organizations

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(R)-Zinc-3573

Probe Availability

Probe Information

Target Details

MGRG3, MRGX2

Probe Details

Physico-chemical properties

In cell validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?