PHA-680632
作者：齊岳
發布時間：2023-08-28
09:00:55
點擊數：
產品名稱：PHA-680632
產品描述：
| 產品描述 | PHA-680632 is 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. |
| 靶點活性 | Aurora A:27 nM, Aurora B:135 nM, Aurora C:120 nM |
| 體外活性 | 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] |
| 體內活性 | 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] |
| 激酶實驗 | 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. |
| 細胞實驗 | 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) |
| 別名 | PHA 680632, PHA680632 |
| 分子量 | 501.635 |
| 分子式 | C28H35N7O2 |
| CAS No. | 398493-79-3 |
存儲
Powder: -20°C for 3 years | In solvent: -80°C for 2 years
溶解度
Ethanol: <1 mg/mL
DMSO: 93 mg/mL (185.4 mM)
H2O: <1 mg/mL
( < 1 mg/mL refers to the product slightly soluble or insoluble )
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公司介紹：
西安齊岳生物科技有限公司是集化學科研和定制與一體的高科技化學公司。業務范圍包括化學試劑和產品的研發、生產、銷售等。涉及產品為通用試劑的分銷、非通用試劑的定制與研發，涵蓋生物科技、化學品、中間體和化工材料等領域。
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