Barasertib, also known as AZD1152, is the precursor to Barasertib-hQPA and is a potent inhibitor of Aurora B kinase, demonstrating an IC50 value of 0.37 nM in cell-free assays. It is known to halt cell proliferation and promote apoptosis in various cancer cells. When applied to freshly isolated leukemia cells at a concentration of 3 μM for 3 hours, Barasertib-HQPA markedly reduces the levels of phosphorylated histone H3[1]. Barasertib-hydroxyquinazoline pyrazol anilide (HQPA) is swiftly transformed into the active form, Barasertib-HQPA, within the plasma[2]. Barasertib-HQPA elicits a significant anti-proliferative response, resulting in the emergence of a polyploid cell population, often culminating in apoptosis[3].
Barasertib 细胞实验
Cell Line
Concentration
Treated Time
Description
References
PC9-ER
0.06 µM
72 h
Barasertib showed strong antiproliferative effects with IC50 < 0.06 µM
Nat Commun. 2019 Apr 18;10(1):1812
PC9-GR3
0.05 µM
72 h
Barasertib showed strong antiproliferative effects with IC50 < 0.06 µM
Nat Commun. 2019 Apr 18;10(1):1812
PC9-GR1-AZD4
0.03 µM
72 h
Barasertib showed strong antiproliferative effects with IC50 < 0.06 µM
Nat Commun. 2019 Apr 18;10(1):1812
PC9-GR1-AZD3
0.03 µM
72 h
Barasertib showed strong antiproliferative effects with IC50 < 0.06 µM
Nat Commun. 2019 Apr 18;10(1):1812
PC9-GR1-AZD2
0.03 µM
72 h
Barasertib showed strong antiproliferative effects with IC50 < 0.06 µM
Nat Commun. 2019 Apr 18;10(1):1812
PC9-GR1-AZD1
0.04 µM
72 h
Barasertib showed strong antiproliferative effects with IC50 < 0.06 µM
Nat Commun. 2019 Apr 18;10(1):1812
BT-474
8 nM
AZD1152-HQPA inhibited cell proliferation
Mol Cancer. 2010 Feb 22;9:42
MDA-MB-361
70 nM
AZD1152-HQPA inhibited cell proliferation
Mol Cancer. 2010 Feb 22;9:42
MDA-MB-231
105 nM
AZD1152-HQPA inhibited cell proliferation and induced apoptosis
Mol Cancer. 2010 Feb 22;9:42
MDA-MB-435
125 nM
AZD1152-HQPA inhibited cell proliferation
Mol Cancer. 2010 Feb 22;9:42
MDA-MB-468
14 nM
AZD1152-HQPA inhibited cell proliferation
Mol Cancer. 2010 Feb 22;9:42
HER18
20 nM
48 h
AZD1152-HQPA inhibited Aurora B kinase activity, leading to mitotic catastrophe, polyploidy, and apoptosis
Mol Cancer. 2010 Feb 22;9:42
11-18-GR5
0.06 µM
72 h
Barasertib showed strong antiproliferative effects with IC50s in the nM range
Nat Commun. 2019 Apr 18;10(1):1812
11-18-GR3
0.06 µM
72 h
Barasertib showed strong antiproliferative effects with IC50s in the nM range
Nat Commun. 2019 Apr 18;10(1):1812
PC9-GR5
0.04 µM
72 h
Barasertib showed strong antiproliferative effects with IC50 < 0.06 µM
Nat Commun. 2019 Apr 18;10(1):1812
Cord blood Lin− cells
10 nM, 100 nM, 1000 nM
2 weeks
AZD1152-HQPA showed a dose-dependent effect on the growth and differentiation of cord blood progenitor cells, with no colonies detected at 1000 nM.
Cancer Res. 2009 May 15;69(10):4150-8
THP-1 cells
100 nM
96 h
THP-1 cells showed a low apoptotic response to AZD1152-HQPA, with more than 80% of cells remaining polyploid at 100 nM and exhibiting senescence-associated β-galactosidase activity.
Cancer Res. 2009 May 15;69(10):4150-8
HL-60 cells
0–1000 nM
96 h
AZD1152-HQPA exerted anti-proliferative or cytotoxic effects in all cell lines studied, inhibited the phosphorylation of histone H3 (pHis H3) on ser10 in a dose dependent manner and resulted in cells with more than 4N DNA content.
Cancer Res. 2009 May 15;69(10):4150-8
PAH-PASMCs
0.5 μM
48 h
To evaluate the effect of Barasertib on proliferation and apoptosis of PAH-PASMCs. Results showed that Barasertib dose-dependently reduced proliferation of PAH-PASMCs (assessed by EdU incorporation and Ki67 labeling) and significantly decreased the resistance of PAH-PASMCs to apoptosis under serum starvation (assessed by Annexin V and TUNEL labeling).
Cell Rep Med. 2025 Feb 18;6(2):101964
mouse lung fibroblasts
5 μM
48 h
To assess the effect of Barasertib on fibroblast proliferation, results showed Barasertib significantly reduced BrdU incorporation
EMBO Mol Med. 2020 Sep 7;12(9):e12131
human IPF lung fibroblasts
5 μM
48 h
To assess the effect of Barasertib on fibroblast proliferation, results showed Barasertib significantly reduced BrdU incorporation
EMBO Mol Med. 2020 Sep 7;12(9):e12131
Barasertib 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
NSG mice
Patient-derived xenograft model
Oral gavage and intraperitoneal injection
25 mg/kg
Once daily, 3 days on and 4 days off
Evaluate the inhibitory effect of TAZ and barasertib combination on tumor growth
Cancer Discov. 2024 Jun 3;14(6):965-981.
Rats
MCT-induced PAH model
Intraperitoneal injection
30 mg/kg
Three times a week from day 14 to 28
To evaluate the therapeutic effect of Barasertib in MCT-induced PAH rats. Results showed that Barasertib significantly reduced right ventricular hypertrophy (assessed by Fulton index) and right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) (assessed by right heart catheterization). Additionally, Barasertib significantly attenuated vascular remodeling in distal pulmonary arteries (assessed by Elastica van Gieson staining).
Cell Rep Med. 2025 Feb 18;6(2):101964
NOD/SCID mice
HL-60 cell xenograft model
Subcutaneous osmotic pump
25 mg/kg/day
1 week continuously
AZD1152 at 25 mg/kg/day significantly reduced the growth of HL-60 cell xenografts, with no regrowth observed post-treatment.
Cancer Res. 2009 May 15;69(10):4150-8
Nude mice
Breast cancer xenograft model
Intraperitoneal injection
62.5 mg/kg and 125 mg/kg
Every 7 days for a cycle, administered on days 1 and 2, total of 3 cycles
2 consecutive days, once daily, followed by a 24-hour gap
To investigate the anti-tumour efficacy of Barasertib in combination with the MEK inhibitor selumetinib. Results showed enhanced tumour growth inhibition and increased cell death when Barasertib was administered before selumetinib.
Br J Cancer. 2012 Feb 28;106(5):858-66
Mice
TGFα-induced pulmonary fibrosis model
Intraperitoneal injection
40 mg/kg body weight
Twice a day for 4 weeks
To evaluate the preventive effect of Barasertib on pulmonary fibrosis, results showed Barasertib significantly reduced collagen deposition and lung weight
EMBO Mol Med. 2020 Sep 7;12(9):e12131
Nude mice
AA TNBC xenograft model
Intraperitoneal injection
100 mg/kg
Twice weekly for up to 28 days
To evaluate the effect of Barasertib on the growth of AA TNBC xenografts, results showed that Barasertib significantly inhibited the growth of AA TNBC xenografts.
Cell Death Dis. 2023 Jan 10;14(1):12
Barasertib 动物研究
Animal study
Barasertib at a dosage of 25 mg/kg, significantly reduces the growth and mass of tumors treated with AZD1152. Furthermore, Barasertib at 5 mg/kg improves the efficacy of vincristine or daunorubicin in curbing the growth of human MOLM13 leukemic xenografts[1]. When administered at doses ranging from 10 to 150 mg/kg/day, Barasertib effectively hampers the growth of xenografts of human colon, lung, and blood tumors in immunodeficient mice. The average inhibition of tumor growth observed was between 55% to 100%[2].
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