General
Preferred name
CCT241533
Synonyms
CCT 241533 dihydrochloride ()
CCT 241533 ()
GTPL8044 ()
XBJ ()
CCT-241533 ()
CCT241533 (hydrochloride) ()
CCT241533 hydrochloride ()
P&D ID
PD015659
CAS
1262849-73-9
1962925-28-5
1431697-96-9
Tags
available
probe
drug candidate
Drug indication
Solid tumour/cancer
Probe info
Probe type
calculated probe
experimental probe
Probe selectivity
protein-selective
Probe sources
Chemical Probes.org
High-quality chemical probes
Probe Miner (suitable probes)
Probe targets
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
DESCRIPTION CCT241533 hydrochloride is a potent and selective CHK2 inhibitor with an IC50 of 3 nM and a Ki of 1.16 nM[1].
PRICE 245
DESCRIPTION CCT241533 hydrochloride is an effective and selective ATP competitive inhibitor of CHK2 (Ki: 1.16 nM; IC50: 3 nM).
COMMENT This probe has a very good selectivity profile; activity was found for only four kinases (PHK, GCK, MLKI, and MARK3) out of a panel of 85. The X-ray structure shows CCT241533 bound to CHK2 in the kinase domain region at a resolution of 2.3 Angstrom. Selectivity of CCT241533 for CHK2 over CHK1 is 80-fold. Pairing with PARP inhibitors enhances cellular toxicity. No PK data are available; solubility has been indicated in DMSO only. This probe is commercially available up to 100 mg of material, and scaled-up synthesis is possible. Jun 30 2016 - 12:31am; CCT241533 is a potent (biochemical IC50 3 nM) and selective (63-fold vs CHK1, >90% inhibition of 3 out of 85 kinases tested at 1 uM) inhibitor of CHK2. Mechanistic inhibition of CHK2 in cancer cells (HT29) has been demonstrated at concentrations from 1 uM (J Med Chem 2011, 54(2), 580-590) and further cell activity is described (Cancer Res 2011, 71(2), 463-472) at similar concentrations. Jun 30 2016 - 12:31am; CCT241533 is a selective, ATP-competitive CHEK2 inhibitor with biochemical (3 nM) and cellular activity. The compound also inhibits CHEK1 in vitro at 190-245 nM and potentiated the anti-proliferative effect of a PARP inhibitor in p53-minus cancer cells. The compound blocks CHEK2 autophosphorylation in response to DNA damage from bleomycin, etoposide, ionizing radiation in p53-null HT29 and HeLa cells, but not in p53 wild-type A549 cells. CCT241533 did not potentiate the cytotoxicity of bleomycin, however. The compound also blocked CHEK2 activity in three human tumor cell lines HT29 (GI50=1.7 uM), HeLa (GI50=2.2 uM) and MCF7 (GI50=5.1 uM) and protected mouse thymocytes from apoptosis by ionizing radiation.  May 23 2017 - 12:38pm
MOA Inhibitor (Chemical Probes.org)
DESCRIPTION Potent inhibitor of the LFA-1/ICAM interaction (Tocris Bioactive Compound Library)
Cell lines
1
Organisms
0
Compound Sets
15
Cayman Chemical Bioactives
19178
Chemical Probes.org
cct241533
Chemical proteomics reveals the target landscape of 1,000 kinase inhibitors
CZ-OPENSCREEN Bioactive Library
DrugMAP
DMZXFT9
EU-OPENSCREEN Bioactive Compound Library
EOS100051
EUbOPEN Chemogenomics Library
EUB0001216
High-quality chemical probes
PD015659
Kinase Chemogenomic Set (KCGS)
CCT241533
Kinase Inhibitors (best-in-class)
Mcule NIBR MoA Box Subset
MCULE-8739590383
MedChem Express Bioactive Compound Library
HY-14715B
Novartis Chemogenetic Library (NIBR MoA Box)
Probe Miner (suitable probes)
O96017/432350
Tocris Bioactive Compound Library
4968
External IDs
29
Properties
(calculated by RDKit )
Molecular Weight
442.2
Hydrogen Bond Acceptors
8
Hydrogen Bond Donors
4
Rotatable Bonds
6
Ring Count
4
Aromatic Ring Count
3
cLogP
2.93
TPSA
108.76
Fraction CSP3
0.39
Chiral centers
2.0
Largest ring
6.0
QED
0.46
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
CHK2
Checkpoint Kinase (Chk)
CHEK2, MARK3, PHK
CHEK2
Known off targets
PHK, MARK3
Kinase group
CAMK
Pathway
Cell Cycle/DNA Damage
Primary Target
Checkpoint Kinases
MOA
Inhibitor
Checkpoint Kinase 2 (Chk2) Inhibitors
Member status
member
Target class
Protein kinase
Recommended Cell Concentration
None
Source data