BPR1K653 hydrochloride
BPR1K653 hydrochloride is a pan-Aurora kinase inhibitor, with an IC50 of 124.0 nM against Aurora-A and an IC50 of 45.0 nM against Aurora-B. BPR1K653 hydrochloride induces endoreduplication, apoptosis and antiproliferative activity in cancer cells. BPR1K653 hydrochloride can be used in research related to colon cancer and multidrug-resistant cancers.
For research use only. We do not sell to patients.
- CAS No.: 1192754-07-6
- Formula: C30H30Cl2N6O2
- Molecular Weight:577.50
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
All Aurora Kinase Isoforms
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Biological Activity
Description
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Aurora A 124.0 nM (IC50) |
Aurora B 45.0 nM (IC50) |
In Vitro
BPR1K653 hydrochloride is a pan-Aurora kinase inhibitor, with stronger inhibitory activity against purified Aurora-B kinase (IC50 = 45.0 nM) than against purified Aurora-A kinase (IC50 = 124.0 nM)[1].
BPR1K653 (0-10000 nM; administered 1 h after 24 h pretreatment with Nocodazole (HY-13520)) hydrochloride preferentially inhibits Aurora-B (Thr232) autophosphorylation over Aurora-A (Thr288) autophosphorylation in Nocodazole-arrested human colon cancer HCT116 cells, with IC50 values of 23.7 nM and 73.4 nM, respectively[1].
BPR1K653 hydrochloride potently inhibits the viability of human colon cancer cell line HCT116 (IC50 = 70 nM), and exhibits low toxicity toward normal human skin fibroblast cell line Detroit 551 (IC50 = 3.1 μM)[1].
BPR1K653 (10-1000 nM) hydrochloride inhibits aurora kinase activity in HCT116 colon cancer cells, as evidenced by concentration-dependent decreases in the levels of phosphorylated Aurora-A, Aurora-B, Aurora-C and phosphorylated histone H3[2].
BPR1K653 (third-generation culture cycle) hydrochloride potently inhibits the proliferation of various human cancer cell lines, regardless of tissue origin, p53 status, or the expression levels of MDR1 and MRP1 efflux pumps, with an IC50 value range of 4 nM to 135 nM[2].
BPR1K653 (10-20 h after thymidine release) hydrochloride significantly reduces the mitotic index of synchronized HeLa human cervical cancer cells[1].
BPR1K653 hydrochloride is a potent and selective pan-aurora kinase inhibitor, with an IC50 value of 124 nM against Aurora-A and 45 nM against Aurora-B, and exhibits extremely low activity against a panel of non-aurora kinases[2].
BPR1K653 (48 h) hydrochloride induces endoreplication and polyploidy in KB, MDR1-positive KB-VIN10 and HONE-1 human cancer cells in a concentration-dependent manner[2].
BPR1K653 (48 h) hydrochloride downregulates the expressions of phosphorylated histone H3 and cyclin B1 in a concentration-dependent manner in KB, MDR1-positive KB-VIN10 and HONE-1 human cancer cells[2].
BPR1K653 (48 h for Annexin-V, 60 h for caspase-3/-7 imaging, 72 h for TUNEL and PARP cleavage) hydrochloride induces apoptosis in human KB, MDR1-positive KB-VIN10, and HONE-1 cancer cells, which is confirmed by Annexin-V staining, caspase activation, DNA fragmentation, and PARP cleavage[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:HCT116 human colon carcinoma cells
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Concentration:10-1000 nM
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Incubation Time:1 h (after 24 h Nocodazole pretreatment)
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Result:Inhibited autophosphorylation of Aurora-A (Thr288) with an IC50 of 73.4 nM.
Showed stronger inhibition of Aurora-B (Thr232) autophosphorylation with an IC50 of 23.7 nM.
Resulted in a cellular Aurora-A/B IC50 ratio of 3.1/1.
In Vivo
BPR1K653 (15 mg/kg; i.p.; 5 days/week; 3 consecutive weeks) hydrochloride inhibits MDR1-positive KB-VIN10 cervical cancer xenograft growth by ~50% in nude mice[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Nude mice (male, 5-6 weeks old)[2]
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Dosage:15 mg/kg
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Administration:i.p.; 5 days/week; 2 consecutive weeks
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Result:Reduced the percentage of phosphor-Histone H3 positive tumor cells to 10% from controls.
Reduced tumor volume by ~73% compared to controls on day 30.
Induced 55% apoptotic cells in tumor tissue at 12 days post-treatment compared to controls.
Caused body weight loss of less than 10% relative to controls.
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Animal Model:Nude mice (male, 5-6 weeks old)[2]
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Dosage:15 mg/kg
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Administration:i.p.; 5 days/week; 3 consecutive weeks
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Result:Reduced tumor volume by ~50% compared to controls on day 42.
Caused body weight loss of less than 10% relative to controls.
Chemical Information
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CAS No. 1192754-07-6
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Molecular Weight 577.50
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Formula C30H30Cl2N6O2
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SMILES
O=C(NC1=CC=C(C=C1)CCNC2=C3C(OC(C4=CC=CC=C4)=C3Cl)=NC=N2)NC5=CC=CC=C5CN(C)C.Cl
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)