The Aurora family of serine/threonine kinases, which consists of Aurora A, B and C, plays an important role in chromosome alignment, segregation, and cytokinesis during mitosis. AZD1152-HQPA, the active drug form converted from AZD1152 (Barasertib) in human plasma, is a specific Aurora B inhibitor with Ki value of 0.36nM versus 1369nM for A kinase. Consistent with Aurora B kinase inhibition, treatment with AZD1152-HQPA caused a dose-dependent inhibition of histone H3 phosphorylation on Ser10 site, with IC50 of 10.27nM, in SW620 colorectal tumor cells and led to increased polyploidy following a 48-h exposure. This activity of AZD1152-HQPA can also observed in an in vivo study. Administration of AZD1152 at dose ranging in 10-150mg/kg/d via an osmotic mini-pump for 48h inhibited growth in a panel of human tumor xenografts, including SW620, Colo205, A549 and HL-6, suggesting that AZD1152 was active against a variety of solid tumors including colon, breast and lung cancers[1]. AZD1152 also had effect in hematologic malignancies. In the presence of AZD1152-HQPA, the clonogenic growth of freshly isolated leukemia cells tested was effectively inhibited with IC50 values ranging in 1-3nM. Exposure of MOLM13 cells to AZD1152-HQPA (1-10nM) for 24 or 48 hours induced apoptosis in a dose-dependent manner. AZD1152-HQPA alone or combined with vincristine or daunorubicin significantly inhibited the proliferation of MOLM13 cells in murine xenograft model[2].
作用机制
AZD1152-HQPA can bind to the ATP-binding pocket of Aurora B.[2]
Barasertib-HQPA 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HD-MB03
500 nM
5 days
To evaluate the inhibitory effect of Barasertib on the growth and dissemination of HD-MB03 cells in the tissue context, Barasertib significantly reduced tumor volume and proliferation volume
Neoplasia. 2025 Jan;59:101078.
ONS-76
3 µM
24 h
To screen kinase inhibitors for inhibiting MB invasion, Barasertib did not significantly reduce collagen I invasion
Neoplasia. 2025 Jan;59:101078.
HBL
3 nM to 3 μM
3 days
To evaluate the growth inhibitory effect of Barasertib-HQPA on BRAF wild-type cells, results showed significant inhibition of cell proliferation within 3 days.
J Transl Med. 2015 Jan 27;13:26.
LND1
3 nM to 3 μM
3 days
To evaluate the growth inhibitory effect of Barasertib-HQPA on BRAF wild-type cells, results showed significant inhibition of cell proliferation within 3 days.
J Transl Med. 2015 Jan 27;13:26.
MBA72
3 nM to 3 μM
3 days
To evaluate the growth inhibitory effect of Barasertib-HQPA on BRAF-mutated cells, results showed significant inhibition of cell proliferation within 3 days.
J Transl Med. 2015 Jan 27;13:26.
Hmel-1
3 nM to 3 μM
3 days
To evaluate the growth inhibitory effect of Barasertib-HQPA on BRAF-mutated cells, results showed significant inhibition of cell proliferation within 3 days.
J Transl Med. 2015 Jan 27;13:26.
U937 cells
29 nM
72 h
Barasertib-HQPA also exhibited cytotoxicity in U937 cells, inducing polyploidy and apoptosis.
Cancer Sci. 2013 Jul;104(7):926-33.
HL-60/ara-C20 cells
70 nM
72 h
Barasertib-HQPA equally inhibited the growth of HL-60/ara-C20 cells, indicating its efficacy against ara-C-resistant cells.
Cancer Sci. 2013 Jul;104(7):926-33.
HL-60 cells
51 nM
72 h
Barasertib-HQPA induced polyploidy with a subsequent induction of sub-G1 phase apoptosis, indicating the M-phase specific cytotoxicity.
Cancer Sci. 2013 Jul;104(7):926-33.
Barasertib-HQPA 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Zebrafish
Zebrafish larval model
Water administration
2, 4, 6, 8, 10 µM
Daily administration until 5 dpf
To evaluate the developmental toxicity of Barasertib in zebrafish larvae, Barasertib did not cause significant developmental toxicity
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