barasertib-hQPA   Click here for help

GtoPdb Ligand ID: 5663

Synonyms: AZD-1152HQPA | AZD2811 [1,3] | INH 34
PDB Ligand
Compound class: Synthetic organic
Comment: This is the active form of the phosphate pro-drug barasertib. It is an inhibitor of Aurora kinase B [4].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 8
Hydrogen bond donors 4
Rotatable bonds 14
Topological polar surface area 128.29
Molecular weight 507.24
XLogP 3.02
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES OCCN(CCCOc1ccc2c(c1)ncnc2Nc1[nH]nc(c1)CC(=O)Nc1cccc(c1)F)CC
Isomeric SMILES OCCN(CCCOc1ccc2c(c1)ncnc2Nc1[nH]nc(c1)CC(=O)Nc1cccc(c1)F)CC
InChI InChI=1S/C26H30FN7O3/c1-2-34(10-11-35)9-4-12-37-21-7-8-22-23(16-21)28-17-29-26(22)31-24-14-20(32-33-24)15-25(36)30-19-6-3-5-18(27)13-19/h3,5-8,13-14,16-17,35H,2,4,9-12,15H2,1H3,(H,30,36)(H2,28,29,31,32,33)
InChI Key QYZOGCMHVIGURT-UHFFFAOYSA-N
References
1. Burris HA, Wang JS, Johnson ML, Falchook GS, Jones SF, Strickland DK, Greenlees C, Brugger W, Charlton J, Pease E et al.. (2017)
A phase I, open-label, first-time-in-patient dose escalation and expansion study to assess the safety, tolerability, and pharmacokinetics of nanoparticle encapsulated Aurora B kinase inhibitor AZD2811 in patients with advanced solid tumours.
Journal of Clinical Oncology, 35 (15): TSP2608.
2. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011)
Comprehensive analysis of kinase inhibitor selectivity.
Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]
3. Floc'h N, Ashton S, Taylor P, Trueman D, Harris E, Odedra R, Maratea K, Derbyshire N, Caddy J, Jacobs VN et al.. (2017)
Optimizing Therapeutic Effect of Aurora B Inhibition in Acute Myeloid Leukemia with AZD2811 Nanoparticles.
Mol Cancer Ther, 16 (6): 1031-1040. [PMID:28292940]
4. Mortlock AA, Foote KM, Heron NM, Jung FH, Pasquet G, Lohmann JJ, Warin N, Renaud F, De Savi C, Roberts NJ et al.. (2007)
Discovery, synthesis, and in vivo activity of a new class of pyrazoloquinazolines as selective inhibitors of aurora B kinase.
J Med Chem, 50 (9): 2213-24. [PMID:17373783]
5. Pollard JR, Mortimore M. (2009)
Discovery and development of aurora kinase inhibitors as anticancer agents.
J Med Chem, 52 (9): 2629-51. [PMID:19320489]
6. Schwartz GK, Carvajal RD, Midgley R, Rodig SJ, Stockman PK, Ataman O, Wilson D, Das S, Shapiro GI. (2013)
Phase I study of barasertib (AZD1152), a selective inhibitor of Aurora B kinase, in patients with advanced solid tumors.
Invest New Drugs, 31 (2): 370-80. [PMID:22661287]
7. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010)
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
Chem Biol, 17 (11): 1241-9. [PMID:21095574]