barasertib-hQPA   

GtoPdb Ligand ID: 5663

Synonyms: AZD-1152HQPA | AZD2811 [1,3] | INH 34
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].
2D Structure
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Physico-chemical Properties
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
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]