PHA-680632

SKU: orb1300855

Description

PHA-680632 is a potent, pan-Aurora kinase inhibitor with IC50 values of 27 nM (Aurora A), 135 nM (Aurora B), and 120 nM (Aurora C). It demonstrates high selectivity, showing 10- to 200-fold less potency against kinases such as FGFR1 and VEGFR2/3. This inhibitor is a valuable chemical probe for studying mitotic progression and cell cycle dysregulation in both cellular and animal cancer models.

Research Area

Cardiovascular Research, Cell Biology, Epigenetics & Chromatin, Metabolism Research, Signal Transduction

Key Properties

• CAS Number: 398493-79-3
• MW: 501.62
• Purity: 99.03% (May vary between batches)
• Formula: C₂₈H₃₅N₇O₂
• SMILES: CCc1cccc(CC)c1NC(=O)N1Cc2[nH]nc(NC(=O)c3ccc(cc3)N3CCN(C)CC3)c2C1
• Target: FGFR,PLK,Aurora Kinase
• Solubility: Ethanol:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (6.58 mM);DMSO:93 mg/mL (185.4 mM);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  Aurora A:27 nM|Aurora B:135 nM|Aurora C:120 nM
• 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.
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• 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. 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.
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• Cell Research:
  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(Only for Reference)
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

AuroraKinase, Aurora Kinase, Aurora C, Aurora A, Aurora B, Inhibitor, FGFR1, inhibit, PHA 680632, PHA680632, PHA-680632, PLK1

Compound Identifiers

PubChem CID

11249084