WM-1119

Protein target name:

KAT6A

Mechanism of action:

HAT inhibitor

Recommended Concentration for use in cells:

up to 1 uM

Probe Availability

TOCRIS

MedChemExpress

Probe Information

Target and Probe Information

Target Details

Target class:

Other

Define other target class:

HAT

Subclass:

Lysine Acetyltransferase

HUGO symbol:

HGNC:13013

Entrez gene ID:

7994

Target alias:

MOZ; ARTHS; MRD32; MYST3; MYST-3; ZNF220; RUNXBP2; ZC2HC6A

Probe Details

Chemical Probes Portal ID:

CPP1837

Probe alias:

WM 1119, Compound-4

PubChem CID:

133080719

SMILES string:

C1=CC=C(C(=C1)F)S(=O)(=O)NNC(=O)C2=CC(=CC(=C2)C3=CC=CC=N3)F

InChi Key:

QLXULUNLCRKWRD-UHFFFAOYSA-N

Control compound:

Compound 187Compound 188Compound 189

Physico-chemical properties

Solubility - concentration:

25-50 ug/ml

NMR:

1H NMR (400 MHz, DMSO-d6) δ = 10.98 (brs, 1H), 10.43 (brs, 1H), 8.71 (d, J = 4.4 Hz, 1H), 8.31 (s, 1H), 8.13–8.02 (m, 2H), 7.96 (t, J = 7.7 Hz, 1H), 7.82 (t, J = 7.3 Hz, 1H), 7.70 (dd, J = 12.7, 7.3 Hz, 1H), 7.54 (d, J = 9.8 Hz, 1H), 7.43 (dd, J = 17.4, 7.9 Hz, 2H), 7.31 (t, J = 7.6 Hz, 1H).

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50, KD

6.3 nM IC50, 2 nM KD

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

6CT2

Structure-activity relationship:

yes, see DOI: 10.1021/acs.jmedchem.9b02071

Off target activity

Selectivity against non-family targets:

WM-1119 is 1,100-fold and 250-fold more active against KAT6A than against KAT5 or KAT7

In cell validation

On target activity in cells

Potency in cells:

IC50

0.250 uM

Potency assay (cells):

Cell cycle analysis, Western

Target engagement assay (cells):

> 1 µM G1 cell cycle arrest

Off target activity in cells

Selectivity against nonfamily targets (cells):

No affinity on off-target panel of 159 diverse targets at 1 or 10 µM

In vivo validation

Organism:

Rat

Dose:

2.9 (IV) mg/kg33 (PO) mg/kg

Route of delivery:

IntravenousOral

Plasma half life:

7.7 h (IV), 6.4 h (PO)

Systemic clearance:

21 mL/min/kg

Cmax:

2.9 uM

Tmax:

1 h

Primary Reference

Reference (doi):

10.1021/acs.jmedchem.9b02071 10.1038/s41586-018-0387-5

Reference (PMID):

32118427 30069049

WM-1119

Probe Availability

Probe Information

Target Details

MOZ; ARTHS; MRD32; MYST3; MYST-3; ZNF220; RUNXBP2; ZC2HC6A

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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WM-1119

Probe Availability

Probe Information

Target Details

MOZ; ARTHS; MRD32; MYST3; MYST-3; ZNF220; RUNXBP2; ZC2HC6A

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?