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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
Structure of DEFOSBARASERTIB

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)

HIDE SMILES / InChI

Molecular Formula C26H30FN7O3
Molecular Weight 507.5599
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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 TargetPharmacologyConditionPotency
0.37 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

PubMed

Sample Use Guides

In Vivo Use Guide
Rats: 25 mg/kg/d as a daily i.v. bolus dose for 4 consecutive days
Route of Administration: Intravenous
In Vitro Use Guide
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
Substance Class Chemical
Record UNII
29P8LWS24N
Record Status Validated (UNII)
Record Version