PHA-680632

Catalog No.S1454 Batch:S145401

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Technical Data

Formula

C28H35N7O2
Molecular Weight 501.62 CAS No. 398493-79-3
Solubility (25°C)* In vitro DMSO 100 mg/mL (199.35 mM)
Ethanol 100 mg/mL (199.35 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description PHA-680632 is a potent inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 27 nM, 135 nM and 120 nM, respectively. It has 10- to 200-fold higher IC50 for FGFR1, FLT3, LCK, PLK1, STLK2, and VEGFR2/3.
Targets
Aurora A [1] Aurora C [1] Aurora B [1] FGFR1 [1] PLK1 [1] View More
27 nM 120 nM 135 nM 390 nM 780 nM
In vitro PHA-680632 potently inhibits all three Aurora kinases (A, B, and C) with IC50 values of 27, 135, and 120 nM, respectively. PHA-680632 is selective for Aurora kinases, with 10- to 200-fold higher IC50 for FGFR1, FLT3, LCK, PLK1, STLK2, VEGFR2, and VEGFR3, and with IC50 higher than 10 μM for another 22 kinases. PHA-680632 shows potent anti-proliferative effects in a wide range of cell types with IC50 values of 0.06–7.15 μM, including HeLa, HCT116, HT29, LOVO, DU145, and NHDF cells. PHA-680632 (0.5 μM) causes polyploidy in tumor cells. The mechanism of action of PHA-680632 is in agreement with inhibition of Aurora kinases. [1] PHA680632 in association with radiation leads to additive effects in cancer cells, especially in the p53-deficient cells. Combined ionising radiation (IR) and treatment of PHA680632 (100–400 nM) prior to IR leads to an enhancement of radiation-induced Annexin V positive cells, micronuclei formation, and Brca1 foci formation only in HCT116 cells with deficient p53, other than the p53 wild-type counterparts. [2]
In vivo HA-680632 (15–60 mg/kg) inhibits tumor growth in mice xenografts models of HL60, A2780, and HCT116 cells, by reducing tumor cell proliferation and increasing apoptosis. PHA-680632 (45 mg/kg) suppresses growth of activated ras-driven mammary tumors in mouse mammary tumor virus v-Ha-ras transgenic mice and results in complete tumor stabilization and partial regression. [1]

Protocol (from reference)

Kinase Assay:[1]
  • Aurora Kinase Inhibition Assay

    Inhibition of kinase activity by PHA-680632 is assessed using a scintillation proximity assay format. The biotinylated substrate is transphosphorylated by the kinase in presence of ATP traced with γ33-ATP. The phosphorylated substrate is then captured using streptavidin-coated scintillation proximity assay beads and the extent of phosphorylation is evaluated by β-counter after a 4-hour rest for the floatation of the beads on a dense 5 M CsCl solution. In particular, a peptide derived from the Chocktide sequence (LRRWSLGL) is used as substrate for Aurora A, whereas the optimized peptide Auroratide is employed for Aurora B and C. The assay is run in a robotized format on 96-well plates. The potency of the compound toward Aurora kinases is evaluated and IC50 values are determined.
Cell Assay:[1]
  • Cell lines

    HeLa, HCT116, HT29, LOVO, DU145, and NHDF cells

  • Concentrations

    0.001-1 μM, dissolved in DMSO as 10 mM stock solution

  • Incubation Time

    72 hours

  • Method

    Cells (5 × 103 to 1.5 × 104 per cm2) are seeded in 24-well plate. After 24 hours, plates are treated with PHA-680632 and incubated for 72 hours. At the end of incubation time, cells are detached from each plate and counted using a cell counter. IC50s are calculated using percentage of growth versus untreated cont
Animal Study:[2]
  • Animal Models

    Mice (female athymic nude) xenografts models of p53−/− HCT116 cells

  • Dosages

    40 mg/kg

  • Administration

    Intraperitoneal (i.p.) injection twice a day

Customer Product Validation

Data from [Data independently produced by Cancer Res, 2013, 73(10), 3168-80]

Data independently produced by , , Dr. Zhang of Tianjin Medical University

Selleck's PHA-680632 has been cited by 14 publications

Aurora kinase A regulates cancer-associated RNA aberrant splicing in breast cancer [ Heliyon, 2023, 9(7):e17386] PubMed: 37415951
Nuclear Aurora kinase A switches m6A reader YTHDC1 to enhance an oncogenic RNA splicing of tumor suppressor RBM4 [ Signal Transduct Target Ther, 2022, 7(1):97] PubMed: 35361747
FOP Negatively Regulates Ciliogenesis and Promotes Cell Cycle Re-entry by Facilitating Primary Cilia Disassembly [ Front Cell Dev Biol, 2020, 8:590449] PubMed: 33304902
Endothelial Cells Promote Colorectal Cancer Cell Survival by Activating the HER3-AKT Pathway in a Paracrine Fashion. [ Mol Cancer Res, 2019, 17(1):20-29] PubMed: 30131447
Targeted Polo-like Kinase Inhibition Combined With Aurora Kinase Inhibition in Pediatric Acute Leukemia Cells. [ J Pediatr Hematol Oncol, 2019, 41(6):e359-e370] PubMed: 30702467
HDAC2 promotes loss of primary cilia in pancreatic ductal adenocarcinoma. [ EMBO Rep, 2017, 18(2):334-343] PubMed: 28028031
Lineage specificity of primary cilia in the mouse embryo. [Bangs FK, et al. Nat Cell Biol, 2015, 17(2):113-22]
Lineage specificity of primary cilia in the mouse embryo. [ Nat Cell Biol, 2015, 17(2):113-22] PubMed: 25599390
Aurora Kinases as Druggable Targets in Pediatric Leukemia: Heterogeneity in Target Modulation Activities and Cytotoxicity by Diverse Novel Therapeutic Agents [Jayanthan A, et al. PLoS One, 2014, 9(7):e102741] PubMed: 25048812
Primary cilia in stem cells and neural progenitors are regulated by neutral sphingomyelinase 2 and ceramide. [He Q, et al Mol Biol Cell, 2014, 25(11):1715-29] PubMed: 24694597

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.