General
Preferred name
barasertib
Synonyms
AZD1152-HQPA ()
AZD-1152 ()
AZD1152 ()
AZD-2811 ()
AZD 1152 ()
BARASERTIB (WHO-DD) ()
AZD 1152 (hydrochloride) ()
Barasertib ()
P&D ID
PD036155
CAS
722543-31-9
722543-50-2
Tags
available
probe
prodrug
drug candidate
Drug Status
investigational
Max Phase
3.0
Drug indication
Acute myeloid leukemia
Probe info
Probe type
calculated probe
experimental probe
P&D approved
Probe selectivity
protein-selective
Probe sources
Probe targets
[[ compound.targets[t].gene_name ]]
Probe control
Probe control not defined
Orthogonal probes
80
No orthogonal probes found
Similar probes
6
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
COMMENT
I would like to see a more comprehensive screen of this probe against more than 50 kinases to confirm its broad selectivity. IC50 is listed at 0.37 nM. It is ~3700-fold more selective for Aurora B over Aurora A. AZD1152-HQPA is the active metabolite of AZ1152. Jun 11 2016 - 4:33am; AZD1152 is a phosphate pro-drug that is rapidly cleaved to the active alcohol. The active alcohol is a potent inhibitor of AURB and AURC. We have dosed AZD1152 in tumor xenograft models in mice using IP administration (100 mg/kg, dosed once daily for 3 consecutive days) and seen robust efficacy in sensitive models (e.g., Lymphoma DOOH2 cell line). The AZD1152 alcohol is significantly less active in P-gp- and BCRP-expressing cell lines, most likely due to drug efflux. Jun 11 2016 - 4:33am; AZD1152 is a phosphate prodrug designed for in vivo studies only. The active form is compound 34 in the corresponding J Med Chem paper, with Aurora B inhibition IC50 <1 nM and the corresponding functional effect in SW620 cells of IC50 17 nM. For in vitro, cell-based studies, Compound 34 should be used since cleavage of the phosphate in AZD1152 might not occur in a cellular system. The compound is very selective based on profiling in the Ambit kinome panel where less than 10 kinases (example EPHB6, FLT3 (more potent than Aurora B)), have a KD within 10X of that for Aurora B. Any kinase reported as an off target within 100X could have functional effect in cellular environment if the Km for ATP is large. Aug 29 2016 - 2:18pm
DESCRIPTION
Barasertib is a pro-drug. The phosphate group is rapidly converted to a hydroxyl group in vivo generating the active form which is a selective inhibitor of aurora kinase B.
(GtoPdb)
DESCRIPTION
Barasertib (AZD1152), a pro-drug of Barasertib-hQPA, is a highly selective Aurora B inhibitor with an IC50 of 0.37 nM in a cell-free assay. Barasertib (AZD1152) induces growth arrest and apoptosis in cancer cells[1].
PRICE
129
MOA
Inhibitor
(Chemical Probes.org)
DESCRIPTION
Barasertib is an orally bioavailable, small-molecule, dihydrogen phosphate prodrug of the pyrazoloquinazoline Aurora kinase inhibitor AZD1152-hydroxyquinazoline pyrazol anilide (AZD1152-HQPA) with potential antineoplastic activity.
(BOC Sciences Bioactive Compounds)
DESCRIPTION
AZD1152 is a pro-drug of Barasertib (AZD1152)-hQPA. Which is a highly selective Aurora B inhibitor with IC50 of 0.37 nM in a cell-free assay.
(TargetMol Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
2
Organisms
0
Compound Sets
19
BOC Sciences Bioactive Compounds
Cayman Chemical Bioactives
ChEMBL Drugs
Chemical Probes.org
Clinical kinase drugs
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
EU-OPENSCREEN Bioactive Compound Library
Guide to Pharmacology
High-quality chemical probes
LINCS compound set
LSP-MoA library (Laboratory of Systems Pharmacology)
LSP-OptimalKinase library (Laboratory of Systems Pharmacology)
MedChem Express Bioactive Compound Library
PKIDB
ReFrame library
TargetMol Bioactive Compound Library
Tool Compound Set
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
40
Molecular Weight
587.21
Hydrogen Bond Acceptors
9
Hydrogen Bond Donors
5
Rotatable Bonds
15
Ring Count
4
Aromatic Ring Count
4
cLogP
3.62
TPSA
174.82
Fraction CSP3
0.31
Chiral centers
0.0
Largest ring
6.0
QED
0.1
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
Serine/threonine-protein kinase Aurora-B
Apoptosis
Aurora B
Aurora Kinase
AURKA, AURKB
Targets
AURKB
MOA
Aurora Kinase inhibitor
Pathway
Cell Cycle/Checkpoint
Chromatin/Epigenetic
Cell Cycle/DNA Damage
Epigenetics
Orthogonal probe
AMG900
Target class
Protein kinase
Kinase
Target subclass
cell cycle-regulated kinase
Source data
