Details
Stereochemistry | ACHIRAL |
Molecular Formula | C26H30FN7O3 |
Molecular Weight | 507.5599 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCN(CCO)CCCOC1=CC2=NC=NC(NC3=NNC(CC(=O)NC4=CC=CC(F)=C4)=C3)=C2C=C1
InChI
InChIKey=QYZOGCMHVIGURT-UHFFFAOYSA-N
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)
DescriptionCurator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/17575233
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/17575233
AstraZeneca and BIND Therapeutics (formerly BIND Biosciences) are collaborating to develop AZD-1152HQPA (AZD2811) for the treatment of cancer. AZD2811, a novel, selective inhibitor of Aurora B kinase that has been shown to be active in both solid and hematological tumors in preclinical models, is the second Accurin candidate to enter clinical development. AZD1152-HQPA is a highly selective Aurora B inhibitor with IC50 of 0.37 nM in a cell-free assay. AZD1152-HQPA inhibited the proliferation of AML lines (HL-60, NB4, MOLM13), ALL line (PALL-2), biphenotypic leukemia (MV4-11), acute eosinophilic leukemia (EOL-1), and the blast crisis of chronic myeloid leukemia K562 cells with an IC50 ranging from 3 nM to 40 nM. The phase 1 trial is enrolling patients with advanced solid tumors, including patients with small cell lung cancer, and is being conducted by AstraZeneca under the companies’ 2013 collaboration agreement with BIND managing all chemistry, manufacturing and control activities.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2185 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17495131 |
0.37 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
---|---|---|
Discovery and development of aurora kinase inhibitors as anticancer agents. | 2009 May 14 |
|
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. | 2010 Nov 24 |
|
Comprehensive analysis of kinase inhibitor selectivity. | 2011 Oct 30 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17575233
Rats: 25 mg/kg/d as a daily i.v. bolus dose for 4 consecutive days
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22382783
Exposure of U251 cells to AZD1152-HQPA from 25 nM to 10 uM for 24 h resulted in a reduction of histone H3 serine 10 phosphorylation and Aurora B autophosphorylation. All GBM cell lines showed a block in cell division with variable reduction in total cell numbers between day 2 and 8 of continuous exposure to 1 uM AZD1152-HQPA
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ACTIVE MOIETY
PRODRUG (METABOLITE ACTIVE)