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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
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Probe Summary

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

References

Publications

Cross References

canSARChEMBLBindingDBPubMed

Vendors

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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...
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