Chemical Probes logo
CCT244747 | CCT244747 : ATP competitive inhibitor of CHEK1
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (3 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
Download

Probe Summary

More...

Targets Biochemical/Biophysical Potency Cellular Potency
CHEK1
  • IC50:7.7 nM
  • IC50:29 nM
ATP competitive
30 - 1000 nM

Selectivity

In Vitro Selectivity Assessment

Potency: IC50 - CHK2 >10,000 nM, CDK1 >10,000 nM

Potency Assay Off-Target:
Inhibition of recombinant, full-length CHK2 and CDK1 kinase activity was determined in a DELFIA assa ...
Selectivity Assessment Description:
We assessed binding/inhibition of eight cardiac ion channels (Millipore Ion Channel CardiacProfil ...
In Cell Selectivity Assessment
Selectivity Assessment Description:
CHK1 inhibition alone is not expected to be cytotoxic in HT29 and SW620 colon cancer cell lines. ...

Potency
Cellular
In Vitro

CHEK1

Mode of Action: ATP competitive

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1158/1078-0432.CCR-12-1322

In Vivo Validations

Mouse
Dose: 25 - 150 mg/kg
Route of delivery: Oral
Plasma half life: BALB/c mice IV (10 mg/kg): 0.67 h, BALB/c mice oral (10 mg/kg): 0.92 h
Systemic clearance: BALB/c mice: 0.125 L/h
Organ of interest (O): HT29 human colon cancer xenograft
Target engagement assay: Target engagement was assessed in vivo by measuring inhibition of gemcitabine-induced CHK1 autophosphorylation on serine 296 (immuno-blot) in HT29 human colon cancer xenografts in CRTac:Ncr-Fox1(nu) athymic mice. At 24 h after gemcitabine +/- CCT244747 treatment, pS296 CHK1 was reduced ~4-fold (p < 0.05) by 100 and 150 mg/kg CCT244747.

DOI Reference: 10.1158/1078-0432.CCR-12-1322

Negative Control Compounds

Not available

Orthogonal Probes def

MK-8776 (SCH 900776)
PF-477736

Chemical Information

Molecular Formula C20H24N8O2
SMILEs COc1cc(Nc2cnc(C#N)c(O[C@H](C)CN(C)C)n2)ncc1-c1cnn(C)c1
InChI InChI=1S/C20H24N8O2/c1-13(11-27(2)3)30-20-16(7-21)22-10-19(26-20)25-18-6-17(29-5)15(9-23-18)14-8-24-28(4)12-14/h6,8-10,12-13H,11H2,1-5H3,(H,23,25,26)/t13-/m1/s1
Molecular weight 408.20 Da
AlogP 2.2248799999999997
HBond acceptors 10
HBond donors 1
Atoms 54

Vendors

Note: This is not an exhaustive list and does not indicate endorsement by the portal.

Expert Reviews

by SERP
(on 23 Oct 2016)
Cellular Use Rating
In Model Organisms
The IC50 for the target kinase, CHK1, is 7.7 nM. The inhibitor was tested versus panel of 140 kinases and showed 50% inhibition against 127 of them and 80% inhibition against 5 at 1,000 nM; no IC50s for...
by SERP
(on 18 May 2017)
Cellular Use Rating
In Model Organisms
In vivo pharmacokinetic (PK) studies show good oral availability, with a more extended half-life compared to iv dosing. Accumulation in tumors was measured. Efficacy of gemcitabine and irinotecan was...
by SERP
(on 11 Sept 2017)
Cellular Use Rating
In Model Organisms
CCT2444747 is a potent CHK1 inhibitor (IC50=7.7 nM) with high selectivity over CHK2 and CDK1 (IC50 >10 uM). Depending on the cell line, off-target antiproliferative effects can be seen at fairly low...
Note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars. Read more about our evaluation criteria