CAS NO: | 885325-71-3 |
规格: | ≥98% |
包装 | 价格(元) |
5mg | 电议 |
50mg | 电议 |
100mg | 电议 |
250mg | 电议 |
500mg | 电议 |
1g | 电议 |
Molecular Weight (MW) | 431.91 |
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Formula | C20H19ClFN5OS |
CAS No. | 885325-71-3 |
Storage | -20℃ for 3 years in powder form |
-80℃ for 2 years in solvent | |
Solubility (In vitro) | DMSO: 86 mg/mL (199.1 mM) |
Water: <1 mg/mL | |
Ethanol: 1 mg/mL (2.3 mM) | |
Other info | Chemical Name: (3-chloro-2-fluorophenyl)(4-((6-(thiazol-2-ylamino)pyridin-2-yl)methyl)piperazin-1-yl)methanone. InChi Key: YCRFPWKUUNKNDN-UHFFFAOYSA-N InChi Code: InChI=1S/C20H19ClFN5OS/c21-16-5-2-4-15(18(16)22)19(28)27-10-8-26(9-11-27)13-14-3-1-6-17(24-14)25-20-23-7-12-29-20/h1-7,12H,8-11,13H2,(H,23,24,25) SMILES Code: O=C(C1=CC=CC(Cl)=C1F)N2CCN(CC3=NC(NC4=NC=CS4)=CC=C3)CC2 |
Synonyms | MK 8745; MK8745; MK-8745 |
In Vitro | In vitro activity: MK-8745 leads to cell cycle arrest at the G2/M phase with accumulation of tetraploid nuclei followed by cell death in non-Hodgkin lymphoma (NHL) cell lines. Treatment with MK-8745 induces p21(waf1/cip1) and CycB1, indicating cell cycle arrest and an increase in the G2/M phase cell population. Following MK-8745 treatment, Aurora-A substrates (TACC3, Eg5 and TPX2) are rapidly degraded following the reduction of phospho-Aurora-A. MK8745 induces apoptotic cell death in a p53-dependent manner when tested in vitro in cell lines of multiple lineages. Exposure of p53 wild-type cells to MK8745 results in the induction of p53 phosphorylation (ser15) and an increase in p53 protein expression. p53-dependent apoptosis by MK8745 is further confirmed in HCT 116 p53(-/-) cells transfected with wild-type p53. Kinase Assay: MK-8745 is a novel, potent and selective Aurora A inhibitor with IC50 of 0.6 nM, 450-fold more selective for Aurora A over Aurora B. Cell Assay: When tested with p53-/+ cell lines, MK-8745 treatment induced apoptotic cell death in a p53-dependent manner through inhibiting Aurora A activity. In non-Hodgkin lymphoma (NHL) cell lines, MK-8745 treatment arrested cell cycle in G2/M phase and induced cell death via inhibiting Aurora A kinase. In HCT 116 Puma (-), HCT116 p21 (-), HCT116 Bax(-) and HCT116 Chk2(-) cell lines, MK-8745 treatment induced cell apoptosis with the percent of 25%, 22%, 25%, and 22%, respectively. |
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In Vivo | NA |
Animal model | NA |
Formulation & Dosage | |
References | Leuk Lymphoma. 2012 Mar;53(3):462-71; Cell Cycle. 2012 Feb 15;11(4):807-17. |
MK8745 is a selective inhibitor of Aurora A kinase. Cell Cycle. 2012 Feb 15;11(4):807-17. | Cell cycle effect and induction of apoptosis by MK8745 (5 μM) in isogenic variants of HCT-116 cells (parental, p53–/–, p21–/–). (A) Flow cytometry analysis of the HCT 116 (top) and its isogenic variants; p21–/– (middle) and p53–/– (bottom) upon exposure to MK for different time points (6, 17, 22, 30 and 40 h) and exposure to ABI (100 nM AZD 1152) for 40 h after Propidium Iodide staining. Cell Cycle. 2012 Feb 15;11(4):807-17. | Downregulation of Aurora A recapitulates the effects of MK8745. Cell Cycle. 2012 Feb 15;11(4):807-17. |