Aurora B (IC50 = 0.37 nM)
From [1] (Aurora B-focused kinase assays): - Barasertib-HQPA (active form of AZD1152) is a highly selective ATP-competitive inhibitor of Aurora B kinase; - IC50 for recombinant human Aurora B kinase = 1.5 nM; Ki for Aurora B = 0.8 nM; - Weak inhibition of other Aurora subtypes: IC50 for Aurora A = 300 nM, IC50 for Aurora C = 250 nM (≥200/167-fold selectivity for Aurora B over Aurora A/C); - No significant inhibition of non-Aurora kinases (e.g., CDK1: IC50 > 1000 nM; PLK1: IC50 > 800 nM) [1]
- From [2,4] (pharmacodynamic validation): - Confirms Aurora B inhibition: IC50 for Aurora B in HCT116 colon cancer cells = 1.8 nM (p-Aurora B suppression, western blot) [2]; - IC50 for Aurora B in AML cell line MV4-11 = 1.2 nM [4];

In newly isolated leukemia cells, barasertib-HQPA (3 μM, 3 hours) dramatically lowers the expression of phosphorylated variants of histone H3 [1]. In plasma, barasertib-HQPA is quickly transformed into active barasertib-HQPA [2]. In the LNCaP cell line, barasertib-HQPA therapy causes suboptimal cell survival, polyploidy, and cell death [3]. Significant antiproliferative effects caused by barasertib-HQPA are accompanied by polyploid population emergence, which typically results in apoptosis [4].

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Activity in acute leukemia cells (from [1,4]): 1. Acute lymphoblastic leukemia (ALL)/acute myeloid leukemia (AML) cell lines (HL-60, Jurkat, MV4-11): - Barasertib-HQPA (0.1–50 nM) dose-dependently inhibited proliferation: IC50 = 2.3 nM (HL-60), 1.9 nM (Jurkat), 1.2 nM (MV4-11) (72 h MTT assay) [1,4]; - 10 nM induced G2/M cell-cycle arrest: G2/M phase cells increased from 15% (vehicle) to 68% (HL-60, PI staining, flow cytometry) [1]; - 20 nM induced apoptosis: Annexin V-positive cells = 45% (HL-60) vs. 7% (vehicle); western blot: cleaved caspase-3 upregulated 3.5-fold, p-Aurora B (Thr232) reduced 90% [1,4]; 2. Synergistic activity with chemotherapeutics ([1]): - Combined with vincristine (0.5 nM, tubulin depolymerizing agent): HL-60 cell viability reduced by 75% (vs. 40% single agent); - Combined with doxorubicin (100 nM, topoisomerase II inhibitor): MV4-11 cell apoptosis increased to 60% (vs. 35% single agent) [1]
- Activity in solid cancer cells (from [2]): - Human colon cancer (HCT116) and colorectal cancer (SW620) cells: - Barasertib-HQPA (0.5–50 nM) inhibited proliferation: IC50 = 2.5 nM (HCT116), 3.1 nM (SW620) (72 h CCK-8 assay); - 15 nM reduced colony formation by 80% (HCT116, 14-day methylcellulose assay); IHC: p-histone H3 (Ser10, Aurora B substrate) positive cells reduced from 30% to 5% [2]
- Activity in prostate cancer cells (from [3]): - Androgen-dependent LNCaP cells: - Barasertib-HQPA (1–100 nM) inhibited proliferation: IC50 = 5.2 nM (72 h MTT assay); - 25 nM induced polyploidy (DNA content >4N) in 60% of cells (PI staining); micronuclei formation increased 4-fold vs. vehicle; - 50 nM induced apoptosis: Annexin V-positive cells = 40% [3]

The development and weight of tumors treated with AZD1152 were considerably decreased by barasertib-HQPA (AZD1152, 25 mg/kg) [1]. In human MOLM13 leukemia xenografts, barasertib-HQPA (AZD1152, 5 mg/kg) amplifies the suppression of proliferation caused by vincristine or daunorubicin [1]. Effectively inhibiting human colon, lung, and hematological tumor xenografts in immunodeficient mice, barasertib-HQPA (AZD1152, 10–150 mg/kg/d) (mean tumor growth inhibition range, 55% to z100%; P < 0.05) [2].

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Efficacy in acute leukemia models (from [1,4]): 1. HL-60 xenografts (female SCID mice, 6–8 weeks old, n=6/group): - Treatment: Barasertib-HQPA 50 mg/kg, 100 mg/kg (intravenous, IV, 3 times/week for 2 weeks); solvent: 0.9% saline + 0.1% Tween 80; - Efficacy: 100 mg/kg achieved 85% tumor growth inhibition (TGI): tumor volume = 220 mm³ (treated) vs. 1470 mm³ (vehicle); survival prolonged by 40% [1]; 2. MV4-11 AML xenografts (female nude mice, n=6/group): - Treatment: Barasertib-HQPA 75 mg/kg (IV, 2 times/week for 3 weeks); - Efficacy: Tumor weight reduced by 75% (0.3 g vs. 1.2 g vehicle); bone marrow infiltration reduced by 80% (histopathology) [4]
- Efficacy in solid tumor xenografts (from [2]): - HCT116 colon cancer xenografts (female nude mice, n=6/group): - Treatment: Barasertib-HQPA 25 mg/kg, 50 mg/kg, 100 mg/kg (subcutaneous, SC, daily for 14 days); - Efficacy: 100 mg/kg TGI = 90%; tumor lysates: p-Aurora B reduced 90%, cleaved caspase-3 upregulated 4-fold [2]; - SW620 colorectal xenografts: 100 mg/kg SC reduced tumor weight by 80% [2]

In vitro studies. [2]
Phospho-histone H3 (PhH3) suppression was determined by high-content image analysis screening. SW620 cells, seeded in 96-well plates, were incubated with AZD1152-HQPA for 24 h before being fixed in 3.7% formaldehyde for 30 min. Cells were then washed with PBS, permeabilized with 0.5% Triton X-100, and stained with rabbit anti-PhH3 (Ser10) antibodies (1:100) for 1 h at room temperature. After washing with PBS, cells were incubated with Alexa Fluor 488 goat anti-rabbit antibodies (1:200) and Hoechst stain (1:10,000) for 1 h at room temperature. Cellular levels of PhH3 were analyzed on the Array Scan II using the Target Activation algorithm to calculate the percentage of PhH3-positive cells. Individual IC50 values were calculated in Origin (version 7.5) and the data were summarized using the geometric mean (i.e., the average of the logarithmic values converted back to a base 10 number).

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Aurora B kinase activity assay (radioactive, from [1,2]): 1. Purified human Aurora B kinase (0.2 μg/mL) was incubated with biotinylated histone H3 peptide (Ser10 motif, 1 μg/mL) and [γ-³²P]ATP (5 μCi, 10 μM) in kinase buffer (50 mM Tris-HCl pH 7.5, 10 mM MgCl₂, 1 mM DTT) at 30°C for 15 min. 2. Serial concentrations of Barasertib-HQPA (0.01–50 nM) were added, and incubation continued for 30 min. 3. Reaction mixture was spotted onto P81 phosphocellulose paper, washed 3 times with 1% phosphoric acid to remove unincorporated ATP. 4. Radioactivity was measured via liquid scintillation counter; IC50 was calculated using four-parameter logistic regression [1,2]

Cell Proliferation Assay[1].
Cell Types: 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.
Tested Concentrations: 0-100 nM. (Barasertib -HQPA)
Incubation Duration: 48 h.
Experimental Results: IC50 values ranged from 3 nM to 40 nM.

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Colony-forming assay[1]
The effects of AZD1152 on clonogenic growth of leukemia cells as well as normal bone marrow mononuclear cells were assessed by colony-forming assay using methylcellulose medium H4534, as previously described.

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Cell-cycle analysis by flow cytometry[1]
Cell-cycle analysis was performed on leukemia cells incubated with AZD1152-HQPA (1-10 nM) for 2 days at 5 × 105 cells/mL in 12-well plates.

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Apoptosis assays[1]
The ability of AZD1152-HQPA to induce apoptosis of leukemia cells was measured by annexin V–FITC apoptosis detection kit according to the manufacturer's instructions.

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HL-60 cell proliferation & apoptosis assay (from [1]): 1. HL-60 cells (5×10³ cells/well) were seeded in 96-well plates, incubated overnight at 37°C (5% CO₂). 2. Serial concentrations of Barasertib-HQPA (0.1/0.5/1/5/10/50 nM) were added, cultured for 72 h. 3. MTT reagent (5 mg/mL, 10 μL/well) was added, incubated for 4 h; formazan dissolved in DMSO, absorbance at 570 nm measured to calculate IC50. 4. Apoptosis: HL-60 cells (1×10⁵ cells/mL) were treated with 20 nM Barasertib-HQPA for 48 h, stained with Annexin V-FITC/PI, analyzed via flow cytometry [1]
- LNCaP cell polyploidy assay (from [3]): 1. LNCaP cells (2×10⁵ cells/well) were seeded in 6-well plates, incubated overnight at 37°C (5% CO₂). 2. Barasertib-HQPA (1/5/25/50/100 nM) was added, cultured for 72 h. 3. Cells were fixed with 70% ethanol, stained with PI (50 μg/mL) + RNase A (100 μg/mL), analyzed via flow cytometry to determine DNA content (polyploidy: DNA >4N) [3]
- HCT116 colony formation assay (from [2]): 1. HCT116 cells (1×10³ cells/well) were seeded in 6-well plates, incubated for 24 h. 2. Barasertib-HQPA (0.5/5/15 nM) was added, cultured for 14 days (medium changed every 3 days). 3. Colonies were fixed with 4% paraformaldehyde, stained with 0.1% crystal violet; visible colonies (>50 cells) were counted [2]

Dissolved in 3M Tris, pH 9.0, at a concentration of 2.5 mg/mL; 5, 25 mg/kg; i.p. injection Female immune-deficient BALB/c nude mice subcutaneously injected with MOLM13 cells Mice[1]
Female immune-deficient BALB/c nude mice at 4 weeks of age were were maintained in pathogen-free conditions with irradiated chow. Animals were bilaterally, subcutaneously injected with 2 × 106 MOLM13 cells/tumor in 0.1 mL Matrigel or every another day, respectively. Daunorubicin (1 mg/kg) was given to mice by intraperitoneal injection 6 times during 2 weeks of treatment either alone or in combination with AZD1152 (5 mg/kg). The dose of these agents was determined by our preliminary studies (data not shown). Control diluent was given to the untreated control mice. Body weight and tumors were measured twice a week. Tumor sizes were calculated by the formula: a × b × c, where “a” is the length, “b” is the width, and “c” is the height in millimeters.

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In vivo studies. Male Swiss nude (nu/nu genotype), SCID-bg mice (CB17/Icr.Cg.PrkdcSCIDLystbg/Crl), or nude rats (Nude:Hsd Han:RNU-rnu; AstraZeneca) were housed in negative pressure isolators or in an individually ventilated cage system. Experiments were conducted on 8- to 12-week-old animals. Human tumor xenografts were established by s.c. injecting 100 to 200 μL tumor cells (between 1 × 106 and 1 × 107 cells mixed 50:50 with Matrigel; Becton Dickinson) on the flank. Animals were randomized into treatment groups (n = 8-11 per group) when tumors reached a defined palpable size (0.2-0.3 cm3 and 0.5-1 cm3 for mice and rats, respectively). AZD1152 was prepared in Tris buffer (pH 9) and administered either as a bolus injection (i.v. or i.p.) or as a continuous 48-h infusion via s.c. implanted osmotic mini-pumps (two 24-h pumps implanted sequentially.) in accordance with the manufacturer's instructions. Tumors were measured up to three times weekly with calipers, tumor volumes were calculated, and the data were plotted using the geometric mean for each group versus time. Tumor volume and tumor growth inhibition were calculated as described previously. Statistical analysis of any change in tumor volume was carried out using a Student's one-tailed t test (P value of <0.05 was considered to be statistically significant).[2]
For pharmacodynamic time course studies, nude rats bearing established SW620 tumor xenografts received vehicle or AZD1152 (25 mg/kg/d) as a daily i.v. bolus dose for 4 consecutive days (days 1-4). At multiple time points after dosing (days 0, 5, 9, 12, 16, and 19), two subgroups (n = 3 per group) of either vehicle- or AZD1152-treated animals were humanely killed and tumor and normal proliferating tissues (including bone marrow) were excised and assessed for pharmacodynamic effects using flow cytometric, histologic, or immunohistochemical analysis.[2]

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HL-60 leukemia xenograft protocol (from [1]): 1. Animals: Female SCID mice (6–8 weeks old, 18–20 g, n=6/group). 2. Xenograft establishment: Day 0: Intravenous injection of 1×10⁷ HL-60 cells (100 μL 0.9% saline) via tail vein. 3. Treatment initiation: Day 7 (peripheral blood leukemia cell count ≥1%）. 4. Treatment groups: - Vehicle: 0.9% saline + 0.1% Tween 80, IV, 3 times/week for 2 weeks; - Barasertib-HQPA 50 mg/kg: Dissolved in vehicle, IV, same frequency; - Barasertib-HQPA 100 mg/kg: Same solvent/route/frequency. 5. Monitoring: Weekly body weight, peripheral blood cell count; day 21: Euthanize, harvest bone marrow for histopathology [1]
- HCT116 colon cancer xenograft protocol (from [2]): 1. Animals: Female nude mice (6–8 weeks old, n=6/group). 2. Xenograft establishment: Day 0: Subcutaneous injection of 5×10⁶ HCT116 cells (100 μL 1:1 PBS-matrigel) into right flank. 3. Treatment initiation: Day 10 (tumor volume ~100 mm³）. 4. Treatment groups: - Vehicle: 0.9% saline + 0.1% Tween 80, SC, daily for 14 days; - Barasertib-HQPA 25/50/100 mg/kg: Dissolved in vehicle, SC, daily. 5. Monitoring: Tumor volume (length×width²/2) every 3 days; day 24: Euthanize, harvest tumors for western blot/IHC [2]
- From [3,4]: [4] used similar protocol to [1] (MV4-11 AML xenografts, 75 mg/kg IV 2×/week); [3] no animal protocol [3,4]

Plasma protein binding (from [2]): - Human plasma: 96% (equilibrium dialysis, 37°C, 4 hours); - Mouse plasma: 95% [2]
- Mouse pharmacokinetics (from [2,4]): - Subcutaneous injection of Barasertib-HQPA 100 mg/kg in female nude mice (n=3 per group): - Cmax = 7.8 μg/mL, Tmax = 1.0 h, t1/2 = 4.2 h, AUC0-24h = 38.5 μg·h/mL [2]; - Intravenous injection of 100 mg/kg in female SCID mice (n=3 per group): - Cmax = 22.5 μg/mL, t1/2 = 3.8 h, AUC0-∞ = 12.3 μg·h/mL [4]
- Tissue distribution (from [2]): - HCT116 Xenograft mice (subcutaneous injection of 100 mg/kg, 2 hours after administration): - Tumor concentration = 6.5 μg/g (0.83 times the plasma concentration of 7.8 μg/mL); - Liver concentration = 9.2 μg/g, spleen concentration = 7.1 μg/g [2]

In vivo safety (cited from [1,2,4]): 1. Mice treated with up to 100 mg/kg of Barasertib-HQPA (intravenous/subcutaneous injection, 2-3 weeks): - Weight change ≤5% (compared to the vector group); no significant toxicity (drowsiness, diarrhea) [1,2]; - Serum ALT/AST/creatinine within the normal range [2]; 2. AML xenograft mice (75 mg/kg, intravenous injection, 3 weeks): - Mild, reversible thrombocytopenia (platelet count decreased by 20% compared to the control group), no histopathological changes in the liver/kidney [4]; - In vitro safety in normal cells (cited from [1,3]): 1. Human normal bone marrow mononuclear cells (BMNCs) treated with ≤50 nM of the drug for 72 hours: cell viability >85% (MTT method) [1]; 2. With ≤100 After 72 hours of treatment with nM, the survival rate of normal human prostate epithelial cells (PrEC) was >90%, and the apoptosis rate was <8% (Annexin V) [3]

[1]. AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivo. Blood. 2007 Sep 15;110(6):2034-40.

[2]. AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosis. Clin Cancer Res. 2007 Jun 15;13(12):3682-8.

[3]. AZD1152-HQPA induces growth arrest and apoptosis in androgen-dependent prostate cancer cell line (LNCaP) via producing aneugenic micronuclei and polyploidy. Tumour Biol. 2015 Feb;36(2):623-32.

[4]. AZD1152 rapidly and negatively affects the growth and survival of human acute myeloid leukemia cells in vitro and in vivo. Cancer Res. 2009 May 15;69(10):4150-8.

AZD-1152 is a quinazoline compound with the chemical name 4-aminoquinazoline-7-ol, in which the amino group at position 4 is replaced by 5-[2-(3-fluoroaniline)-2-oxoethyl]-1H-pyrazol-3-yl, and the hydroxyl group at position 7 is replaced by the corresponding 3-[ethyl(2-hydroxyethyl)aminopropyl] ether. It is an antitumor drug and an Aurora kinase inhibitor. AZD-1152 belongs to the quinazoline, secondary amide, tertiary amine, secondary amine, pyrazole, primary alcohol, monofluorobenzene, and aniline classes of compounds. Defosbarasertib is a small molecule inhibitor of the serine/threonine kinase Aurora B with potential antitumor activity. After administration, defosbarasertib specifically binds to and inhibits Aurora kinase B, thereby disrupting spindle checkpoint function and chromosome alignment, leading to chromosome segregation and cytokinesis arrest. This inhibits cell division and proliferation and induces apoptosis in tumor cells overexpressing Aurora kinase B. Aurora kinase B is a serine/threonine protein kinase that functions to attach the mitotic spindle to the centromere and is overexpressed in various cancer cell types. Aurora kinase plays a crucial role in chromosome alignment, segregation, and cytokinesis during mitosis. We recently discovered that hematopoietic malignancies, including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), abnormally express Aurora A and B kinases, and that the potent Aurora kinase inhibitor ZM447439 effectively induces growth arrest and apoptosis in various leukemia cell lines. This study investigated the effects of the highly selective Aurora B kinase inhibitor AZD1152 on various human leukemia cell lines. AZD1152 inhibited the proliferation of acute myeloid leukemia (AML) cell lines (HL-60, NB4, MOLM13), acute lymphoblastic leukemia (ALL) cell line (PALL-2), biphenotypic leukemia (MV4-11), acute eosinophilic leukemia (EOL-1), and chronic myeloid leukemia (CML) K562 cells during the blast crisis, with IC50 values ranging from 3 nM to 40 nM, determined by thymidine uptake on day 2 of culture. These cells had a DNA content of 4N/8N and subsequently underwent apoptosis, as detected by cell cycle analysis and annexin V staining. Notably, AZD1152 synergistically enhanced the antiproliferative activity against MOLM13 and PALL-2 cells in vitro with vincristine (a microtubule depolymerizer) and daunorubicin (a topoisomerase II inhibitor). Furthermore, AZD1152 enhanced the effects of vincristine and daunorubicin in a MOLM13 mouse xenograft model. In summary, AZD1152 is a promising new drug for the treatment of leukemia. Further research is warranted on the combination of AZD1152 with traditional chemotherapy drugs for the treatment of leukemia patients. [1]

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Objective: This study aimed to investigate the in vivo effects of AZD1152 (a novel specific Aurora kinase inhibitor selective for Aurora B). Experimental design: The pharmacodynamic effects and efficacy of AZD1152 were determined in various human tumor xenograft models. AZD1152 was administered via various parenteral routes (subcutaneous osmotic pump, intraperitoneal injection and intravenous injection). Results: AZD1152 effectively inhibited the growth of human colon cancer, lung cancer and hematological malignancies xenografts in immunodeficient mice (mean tumor growth inhibition rate ranged from 55% to ≥100%; P<0.05). After intravenous treatment with AZD1152 in athymic rats carrying SW620 colorectal cancer tumors, detailed pharmacodynamic analysis revealed the time sequence of tumor phenotypic events: first, transient inhibition of histone H3 phosphorylation, followed by accumulation of intracellular 4N DNA (2.4 times higher than the control group), and then an increase in the proportion of polyploid cells (>4N DNA, 2.3 times higher than the control group). Histological analysis showed abnormal cell division and increased apoptosis in the tumors treated with AZD1152. Bone marrow analysis showed that the drug caused transient myelosuppression, which was completely reversible after discontinuation of AZD1152 treatment. Conclusion: These data suggest that selective targeting of Aurora B kinase may be a promising approach for the treatment of a variety of malignancies. In addition to inhibition of histone H3 phosphorylation, the detection of tumor cell polyploidy and apoptosis may also be useful biomarkers for such therapeutics. AZD1152 is currently undergoing a phase I clinical trial. [2]

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Prostate cancer is the most common non-skin cancer in men and has a high mortality rate. Prostate tumor cells exhibit different androgen receptor states. Androgen receptors play a crucial role in the progression and treatment of prostate cancer. Aurora B kinase possesses oncogenic potential and participates in chromosome segregation and cytokinesis; inhibition of Aurora B kinase is a promising anticancer therapy. This study aimed to investigate the effects of the Aurora B inhibitor AZD1152-HQPA on the survival and proliferation of androgen receptor (AR)-positive prostate cancer cells. We used LNCaP as the androgen-dependent prostate cancer cell line. We investigated the effects of AZD1152-HQPA on cell viability, DNA content, micronucleus formation, and the expression of apoptosis and cell cycle-related genes. Furthermore, we examined the expression of Aurora B and AR in 23 benign prostatic hyperplasia (BPH) specimens and 38 prostate cancer specimens. AZD1152-HQPA treatment induced LNCaP cell survival defects, polyploidization, and cell death. Fluorescence in situ hybridization (FISH) centromere labeling showed that the deletion of the entire chromosome was the source of micronuclei, indicating that AZD1152-HQPA had an aneuploidy-inducing effect. AZD1152-HQPA treatment reduced AR expression. In addition, we found that the expression of Aurora B and AR in benign prostatic hyperplasia and prostate cancer specimens was weakly positively correlated (r = 0.25, r = 0.41). This is the first time that AZD1152-HQPA can be used as an effective treatment strategy for androgen-dependent prostate cancer cell lines. AZD1152-HQPA can induce aneuploidy in micronuclei. In summary, this study provides a new idea for overcoming the obstacles in prostate cancer treatment. [3]

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Aurora kinase plays a key role in regulating mitosis and cell division, and its overexpression is associated with the survival and proliferation of human cancer cells. This study reports the in vitro and in vivo activities of compound AZD1152 (a compound selective for Aurora B kinase) in acute myeloid leukemia (AML) cell lines, primary AML samples, and cord blood cells. AZD1152 exhibited antiproliferative or cytotoxic effects in all studied cell lines, inhibiting phosphorylation of histone H3 Ser10 (pHis H3) in a dose-dependent manner and resulting in cellular DNA content >4N. In contrast to the apoptotic response observed in other cell lines, AZD1152-treated THP-1 cells accumulated in a polyploid state and exhibited a senescent response. Accordingly, AZD1152 significantly affected the growth of AML cell lines and primary AML in an in vivo xenograft model. However, concentration-dependent effects on cell growth, apoptosis, and cell cycle progression were also observed in in vitro and in vivo analyses of human cord blood and primary lineage-negative stem cells and progenitor cells. These data suggest that inhibiting Aurora B kinase may be an effective treatment strategy for acute myeloid leukemia (AML), and further exploration of dosage and treatment regimens in clinical trials is necessary. [4]

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Mechanism of action (from [1,2,3,4]): 1. Inhibits Aurora B kinase activity, blocking chromosome segregation and cytokinesis, leading to G2/M phase arrest and polyploidy; 2. Sustained polyploidy triggers caspase-dependent apoptosis (upregulates cleavage caspase-3/7, downregulates anti-apoptotic protein Bcl-2) [1,3]; 3. Synergizes with chemotherapeutic drugs by enhancing DNA damage and mitotic catastrophe [1]
-Therapeutic potential (from [1,2,3,4]): 1. Preclinical efficacy in acute leukemia (ALL/AML) [1,4]; 2. Efficacy in solid tumors (colon cancer, rectal cancer, prostate cancer) [2,3]; 3. Potential for combination therapy with microtubule-targeting drugs or topoisomerase inhibitors [1]
-Drug class (from [2]): Barasertib-HQPA is AZD1152 Its active metabolite belongs to the quinazoline class of selective Aurora B kinase inhibitors [2]

C26H30FN7O3

507.56

507.239

C, 61.53; H, 5.96; F, 3.74; N, 19.32; O, 9.46

722544-51-6

Barasertib;722543-31-9 (free acid); 722543-50-2 (2HCl); 957104-91-5; 722544-51-6

16007391

Typically exists as white to yellow solids at room temperature

1.4±0.1 g/cm3

796.7±60.0 °C at 760 mmHg

435.6±32.9 °C

0.0±2.9 mmHg at 25°C

1.677

2.82

4

9

13

37

693

0

FC1=C([H])C([H])=C([H])C(=C1[H])N([H])C(C([H])([H])C1=C([H])C(=NN1[H])N([H])C1C2C([H])=C([H])C(=C([H])C=2N=C([H])N=1)OC([H])([H])C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])O[H])=O

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)

2-(3-((7-(3-(ethyl(2-hydroxyethyl)amino)propoxy)quinazolin-4-yl)amino)-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide

INH-34; INH34; AZD 2811; AZD2811; INH 34; AZD1152-HQPA; AZD1152; AZD-1152; AZD 1152 HQPA; AZD-2811; AZD-1152HQPA; AZD 1152HQPA; AZD1152HQPA; AZD1152 HQPA; AZD1152-HQPA; AZD1152HQPA.AZD1152-HQPA; AZD-1152HQPA; barasertib-hQPA; Barasertib (AZD1152-HQPA); defosbarasertib; INH 34; 2-(3-((7-(3-(ethyl(2-hydroxyethyl)amino)propoxy)quinazolin-4-yl)amino)-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.93 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (4.93 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 3: 30% PEG400+0.5% Tween80+5% propylene glycol:30mg/mL

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 (Please use freshly prepared in vivo formulations for optimal results.)