PF-4800567

Protein target name:

CSNK1E

Mechanism of action:

ATP-competitive inhibitor

Recommended Concentration for use in cells:

N/A

Probe Availability

Tocris (1391052-28-0)

MilliporeSigma (1391052-28-0)

Cayman (1188296-52-7)

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

CK1

HUGO ID:

HGNC:2453

Entrez gene ID:

1454

UNIPROT ID:

P49674

Target alias:

CKIepsilon, HCKIE

Probe Details

Chemical Probes Portal ID:

CPP126

Probe alias:

PF 4800567

PubChem CID:

53472153

ChEMBL ID:

CHEMBL2069623

SMILES string:

C1COCCC1N2C3=C(C(=N2)COC4=CC(=CC=C4)Cl)C(=NC=N3)N

InChi Key:

AUMDBEHGJRZSOO-UHFFFAOYSA-N

PAINs evaluation:

PAINs free

Physico-chemical properties

NMR:

1H NMR (MeOH-d4) δ 8.39 (s, 1H), 7.28 (t, J = 8.2 Hz, 1H), 7.14 (t, J = 2.2 Hz, 1H), 6.96 - 7.05 (m, 2H), 5.49 - 5.61 (m, 2H), 5.02 - 5.11 (sym. mult., 1H), 4.11 (dd, J = 11.1, 4.1 Hz, 2H), 3.64 (dt, J = 12.0, 1.95 Hz, 2H), 2.26 - 2.39 (sym. mult., 2H), 1.90 - 1.99 (sym. mult., 2H); 13C NMR (MeOH-d4) δ 158.3, 152.0, 151.6, 146.2, 144.1, 134.9, 130.6, 122.0, 115.4, 113.5, 98.1, 66.5, 63.8, 54.3, 31.9

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

32 nM

Potency assay:

In vitro kinase assay

Off target activity

Potency (off target):

IC50

Off target protein and potency:

CSNK1D 711 nM

Potency assay (off target):

In vitro kinase assay; 50 additional kinases were tested at 1 and 1 uM. PF-4800567 inhibited 69% of EGFR activity at 1 uM and 83% at 10 uM.

In cell validation

On target activity in cells

Potency in cells:

IC50

0.13 uM

Potency assay (cells):

Inhibition of protein substrate phosphorylation; CSNK1D IC50 = 2.65 uM

Target engagement assay (cells):

Indirect: inhibition of protein substrate phosphorylation

In vivo validation

Organism:

C57BL/J6 mice

Dose:

100 mg/kg

Route of delivery:

Subcutaneous

Ratio of probe in organ to plasma (O:P):

2.1

Fraction of probe bound to plasma protein:

0.95

Cmax:

5250 ng/mL

Tmax:

0.5 hr

Organ of Interest

Organ (O):

Brain

Primary Reference

Reference (doi):

10.1124/jpet.109.151415

Reference (PMID):

19458106

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

3 review(s)

SAB Members

SAB Comments

This probe is weakly active in cells (2.7 uM), and mice dosed subcutaneously show only minor effects due to treatment. This probe needs improvement before using in cellular or in vivo models.

Jun 16 2016 - 5:15pm

The probe has cellular activity at 2.7 uM, but a target potency of triple-digit nM. Selectivity is ~ 20X at the biochemical level and ~ 10X at the cellular level for CK1d/e. No cellular target-engagement data is provided; therefore, it must be assumed to be insufficiently cell-active and insufficiently selective to act as a probe.

Jun 16 2016 - 5:16pm

This compound also significantly inhibits EGFR.

Jan 16 2017 - 2:40pm

PF-4800567

Probe Availability

Probe Information

Target Details

CKIepsilon, HCKIE

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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PF-4800567

Probe Availability

Probe Information

Target Details

CKIepsilon, HCKIE

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?