JQKD82

Protein target name:

KDM5A

Mechanism of action:

Prodrug Inhibitor

Recommended Concentration for use in cells:

up to 1 uM

Probe Information

Target and Probe Information

Target Details

Target class:

Epigenetics

Subclass:

Lysine demethylase

HUGO ID:

HGNC:9886

Entrez gene ID:

5927

UNIPROT ID:

P29375

Target alias:

RBP2; RBBP2; RBBP-2

Probe Details

Chemical Probes Portal ID:

CPP2439

SMILES string:

O=C(OC1=CC=C(OC(C)C)C=C1OC(C)C)C2=CC(CNCC(N(CC)CCN(C)C)=O)=NC=C2

InChi Key:

APYABXFXNNTCQD-UHFFFAOYSA-N

Orthogonal probe:

GSK-J1GSK467

Physico-chemical properties

NMR:

1H NMR (500 MHz , CD3OD): δ = 8.92 (d, J = 5.0 Hz 1H), 8.12 (s, 1H), 8.02 (d, J = 5.0 Hz 1H), 7.02 (d, J = 9.0 Hz, 1H), 6.60 (s, 1H), 6.35 (d, J = 9.0 Hz, 1H), 4.50-4.38 (m, 4H), 4.23 (s, 2H), 3.81-3.78 (m, 2H), 3.42-3.38 (m, 4H), 2.92 (s, 6H), 1.31 (d, J = 6.0 Hz, 3H), 1.24 (t, J = 7.5 Hz, 3H), 1.20 (d, J = 6.0 Hz, 3H).

13C NMR (126 MHz, CD3OD) δ 171.0, 170.2, 163.6, 160.0, 157.0, 149.7, 138.1, 134.3, 122.4, 121.7, 115.1, 108.5, 106.6, 104.1, 71.1, 70.2, 57.0, 56.1, 53.3, 44.4, 43.8, 41.7, 21.1, 21.0, 20.9, 20.9, 12.6, 11.7.

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

7 nM KDM5A

Potency assay:

AlphaLISA Assay

PDB ID for probe-target interaction (3D structure):

5FWJ

Structure-activity relationship:

Off target activity

Potency (off target):

IC50

Off target protein and potency:

4 nM KDM5B, 13 nM KDM5C, 15nM KDM5D

Probe Selectivity in Vitro:

Within Family: 210 nM KDM4C, 1400 nM KDM6C, 780 nM KDM3A, 2200 nM KDM2A

In cell validation

On target activity in cells

Potency in cells:

IC50

420 nM

Potency assay (cells):

Growth inhibition

Target engagement assay (cells):

JQKD82 induced specific increases of H3K4me3, but has no effect with either other histone methylation marks, such as H3K9me3 and H3K27me3, or H3K4me1, which is in agreement with the KDM5 methylation profile.

In vivo validation

Organism:

Mouse

Dose:

50 mg/kg

Route of delivery:

Intraperitoneal

Plasma half life:

6 h

Cmax:

330 uM

Primary Reference

Reference (doi):

10.1158/2643-3230.BCD-20-0108 10.1038/nchembio.2087

Reference (PMID):

34258103 27214403

JQKD82

Probe Information

Target Details

RBP2; RBBP2; RBBP-2

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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JQKD82

Probe Information

Target Details

RBP2; RBBP2; RBBP-2

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?