PD0332991

Reagent Authentication Certificate:

Chemical Probes Portal PD0332991.pdf

Protein target name:

CDK4, CDK6

Mechanism of action:

ATP-competitive inhibitor

Recommended Concentration for use in cells:

3 nM - 3 uM

Probe Availability

MedChem Express (571190-30-2)

Abcam (571190-30-2)

Tocris (571190-30-2)

Cayman (827022-32-2)

MilliporeSigma (827022-33-3)

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

CMGC

HUGO ID:

HGNC:1773 HGNC:1777

Entrez gene ID:

1019 1021

UNIPROT ID:

P11802 Q00534

Target alias:

CMM3, PSK-J3; MCPH12, PLSTIRE

Probe Details

Chemical Probes Portal ID:

CPP144

Probe alias:

Palbociclib

PubChem CID:

5330286

ChEMBL ID:

CHEMBL189963

SMILES string:

CC1=C(C(=O)N(C2=NC(=NC=C12)NC3=NC=C(C=C3)N4CCNCC4)C5CCCC5)C(=O)C

InChi Key:

AHJRHEGDXFFMBM-UHFFFAOYSA-N

PAINs evaluation:

PAINs free

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

CDK4 0.011 uM; CDK6 0.0.16 uM

Potency assay:

Inhibition of substrate-GST fusion phosphorylation

Off target activity

Potency (off target):

IC50

Off target protein and potency:

DUSP1A 2 uMMAPK9 8 uM

Potency assay (off target):

>10 uM for all other kinases tested (CDK1, CDK2, CDK5, EGFR, FGFR, PDGFR, LCK, VEGFR, AMPK, CHEK1, CSNK1, CSNK2, SRC, CSK, GSK3B, JUN, ERK2, MAPKAPK2, MAPK1, MAPK8, RPS6KB1, PDPK1, PHK, PRKACA, AKT1, PRKC, MAPKAPK5, ROCK1, MAPK14, MAP2K6, MAP2K4)

In cell validation

On target activity in cells

Potency in cells:

IC50

0.066 uM

Potency assay (cells):

Inhibition of Rb phosphorylation at Ser780 in MDA-MB-435 breast carcinoma cells

Target engagement assay (cells):

Indirect, inhibition of substrate phosphorylation

Primary Reference

Reference (doi):

Mol Cancer Ther.

Reference (PMID):

15542782

Endorsed probe

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

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

3 review(s)

SAB Members

SAB Comments

PD0332991 leads to complete tumor stasis in a MDA-MB-435 xenograft at 150 mg/kg.

Jun 30 2016 - 12:37am

Additional kinase selectivity data can be found on the MRC website (http://www.kinase-screen.mrc.ac.uk/screening-compounds/348821). Cellular target- engagement studies would strengthen support for using this as a probe and would further link the target to the phenotype.

Sep 4 2016 - 1:58pm

PD0332991

Probe Availability

Probe Information

Target Details

CMM3, PSK-J3; MCPH12, PLSTIRE

Probe Details

In vitro validation

In cell validation

Primary Reference

Supporting Organizations

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PD0332991

Probe Availability

Probe Information

Target Details

CMM3, PSK-J3; MCPH12, PLSTIRE

Probe Details

In vitro validation

In cell validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?