EXEL-1855
EXEL-1855 is an orally active, potent and selective PLK4 inhibitor with an IC50 of 7.7 nM. EXEL-1855 competitively inhibits the catalytic activity of PLK4 by specifically binding to PLK4 (Met91 residue) to block centriole biogenesis, while relieving its ubiquitination-mediated degradation feedback, leading to abnormal protein accumulation and ultimately causing mitotic defects and death of tumor cells. EXEL-1855 can be used for research on neuroblastoma.
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- CAS. Nr.: 3086824-79-2
- Formel: C26H29F7N8O2
- Molecular Weight:618.55
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biologische Aktivität
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Chemical Information
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Biologische Aktivität
Beschreibung
IC50 & Target
[1]|
PLK4 7.7 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| CHP-134 | EC50 |
12 nM
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Inhibition of CHP-134 neuroblastoma cell viability after five-day exposure.
Inhibition of CHP-134 neuroblastoma cell viability after five-day exposure.
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acs.jmedchem.6c01844 |
In Vitro
EXEL-1855 (7-5000 nM; 16 h) induces concentration-dependent accumulation and stabilization of total PLK4 protein levels in MCF7 cells, confirming its targeted inhibition of intracellular PLK4 kinase activity (relieving phosphorylation-dependent autodegradation feedback)[1].
EXEL-1855 (2 h) binds PLK4 in cells with an EC50 of 33 nM[1].
EXEL-1855 has a low hERG risk, with IC50 >20 µM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MCF7 cells
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Concentration:7, 21, 62, 185, 556, 1667, and 5000 nM
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Incubation Time:16 h
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Result:Induced the accumulation and stabilization of total PLK4 protein levels in a dose-dependent manner.
Parmacokinetics
| Species | Dose | Route | CL | Vdss | F | T1/2 | AUClast | Cmax | Tmax |
|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 30 mg/kg | p.o. | / | / | / | 2.2 h | 29 μM·h | 7.1 μM | 1 h |
| Rat[1] | 1 mg/kg | i.v. | 24 mL/min/kg | 4.0 L/kg | / | / | / | / | / |
| Rat[1] | 1 mg/kg | p.o. | / | / | 4 % | 1.6 h | / | / | / |
| Dog[1] | 1 mg/kg | i.v. | 7.7 mL/min/kg | 3.1 L/kg | / | / | / | / | / |
| Dog[1] | 1 mg/kg | p.o. | / | / | 21 % | 6.4 h | / | / | / |
| Cynomolgus Monkey[1] | 1 mg/kg | i.v. | 15 mL/min/kg | 15 L/kg | / | / | / | / | / |
| Cynomolgus Monkey[1] | 1 mg/kg | p.o. | / | / | 15 % | 2.2 h | / | / | / |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:CB-17 SCID (female, 6-8 weeks old)[1]
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Dosage:10 mg/kg; 30 mg/kg; 100 mg/kg
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Administration:p.o.; once daily; 21 days
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Result:Tumor growth inhibition was 20%, 93%, and 106% at 10, 30, and 100 mg/kg, respectively, based on day 21 tumor volumes.
Tumor stasis occurred at 30 mg/kg from day 7 onward.
Tumor regression occurred at 100 mg/kg from day 10 through the end of the 21-day study.
Chemical Information
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CAS. Nr. 3086824-79-2
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Molecular Weight 618.55
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Formel C26H29F7N8O2
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SMILES
O=C(N(CC[C@@](C(F)(F)F)(O)C1)C21CC2)NC3=CNN=C3C(N=C4)=CC5=C4C(N6CC(C6)C(F)(F)F)=NN5CC(C)(C)F
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
EXEL-1855 Related Classifications
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