Chemical Probes logo

PF-477736

PF-477736 : ATP-competitive inhbitor of CHEK1

Structure

Information

  • CHEK1
  • ATP-competitive inhbitor
  • 50 nM - 1 uM

In Vitro Validations

Uniprot ID: O14757
Target Class: Protein kinase
Target SubClass: CAMK
Potency: Ki
Potency Value: 0.49 nM
Potency Assay: In vitro kinase assay with the catalytic domain of CHEK1
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Serine/threonine-protein kinase Chk1, CHK1, CHEK1, ...

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency end-point : IC50 AURA 23 nM, FGFR3 23 nM, FLT3 25 nM, CSF1R 10 nM, RET 39 nM, YES 14 nM, VEGFR2 8 nM (Ki), CHEK2 47 nM (Ki)
Potency assay (off target): >100 kinases were screened, and PF-477136 was >100-fold selective for all other than those indicated.
I have extra information to add

SERP ratings and comments

SERP Ratings

In Cell Rating
In Model Organisms

(last updated: 16 May 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

The compound abrogates cell cycle arrest induced by DNA damage and enhances cytotoxicity of clinically important chemotherapeutic agents, including gemcitabine and carboplatin. It also inhibits VEGFR2, Aurora-A, FGFR3, FLT3, FMS (CSF1R), RET and YES. It shows ~100-fold selectivity for CHK1 over CHK2. PF-477736 (128 nM) abrogates the camptothecin-induced DNA damage checkpoint in CA46 and HeLa cells. PF-477736 (540 nM) enhances gemcitabine-induced cytotoxicity in HT29 cells. PF-477736 (360 nM) suppresses docetaxel-induced phosphorylation of histone H3 (Ser10) and Cdc25C (Ser216) and potentiates apoptosis in COLO205 cells. PF-477736 (250 nM) combined with MK-1775 have synergistic cytotoxic activity in OVCAR-5 cells.

(last updated: 9 Jun 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

This probe is a potent inhibitor of CHK1 in biochemical and cellular assays.

(last updated: 22 Jun 2016 )