INCB127443
INCB127443 is an orally active and selective CDK2/cyclin E1 inhibitor (IC50 = 0.99 nM). INCB127443 is an ATP-competitive inhibitor that blocks Rb phosphorylation and cell cycle progression, and inhibits S-phase progression and proliferation in cyclin E-overexpressing ovarian cancer cells. INCB127443 shows antitumor efficacy and inhibits Rb phosphorylation in a cyclin E-overexpressing ovarian cancer xenograft model. INCB127443 can be used for research related to ovarian cancer.
For research use only. We do not sell to patients.
- CAS No.: 2602667-12-7
- Formula: C24H26ClF4N7O2S
- Molecular Weight:588.02
-
Storage:
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]
-
Biological Activity
-
Chemical Information
- Protocols
- Purity & Documentation
- References
-
Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
CDK2/cyclin E1 0.99 nM (IC50) |
CDK1/cyclinB1 313 nM (IC50) |
Cdk4/cyclin D1 12 nM (IC50) |
CDK5/p35 243 nM (IC50) |
CDK6/D1 22 nM (IC50) |
cdk6/cyclin D3 85 nM (IC50) |
CDK7/H 143 nM (IC50) |
CDK9/T1 3511 nM (IC50) |
CDK12/K 748 nM (IC50) |
CDK13/K 7053 nM (IC50) |
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| OVCAR-3 | IC50 |
518 nM
|
Inhibition of CDK1-dependent NPM T199 phosphorylation in human OVCAR-3 cells.
Inhibition of CDK1-dependent NPM T199 phosphorylation in human OVCAR-3 cells.
|
42911678 |
| JeKo-1 | IC50 |
445 nM
|
Inhibition of CDK4-dependent pRb in human JeKo-1 cells.
Inhibition of CDK4-dependent pRb in human JeKo-1 cells.
|
42911678 |
| CAL-51 | IC50 |
448 nM
|
Inhibition of CDK4-dependent pRb in human CAL-51 cells.
Inhibition of CDK4-dependent pRb in human CAL-51 cells.
|
42911678 |
| MV4-11 | IC50 |
416 nM
|
Inhibition of CDK6-dependent pRb in human MV-4-11 cells.
Inhibition of CDK6-dependent pRb in human MV-4-11 cells.
|
42911678 |
| OVCAR-3 | IC50 |
27 nM
|
Inhibition of S-phase in human OVCAR-3 ovarian cancer cells treated with increasing concentrations of INCB127443.
Inhibition of S-phase in human OVCAR-3 ovarian cancer cells treated with increasing concentrations of INCB127443.
|
42911678 |
| OVCAR-3 | IC50 |
46 nM
|
Inhibition of long-term proliferation in human OVCAR-3 cells measured by confluence-based IncuCyte assay over 14 days.
Inhibition of long-term proliferation in human OVCAR-3 cells measured by confluence-based IncuCyte assay over 14 days.
|
42911678 |
In Vitro
INCB127443 exhibits 20-25-fold cellular selectivity relative to CDK1, CDK4, and CDK6 in tested cells and whole blood models[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
In Vivo
INCB127443 (3-100 mg/kg; p.o.; twice daily or once daily; 24 days) produces dose-dependent antitumor activity in CCNE1-high OVCAR-3 xenograft tumors, with a tumor growth inhibition rate of 83% at 100 mg/kg twice daily[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:athymic nude (female, 4-6-week, 1 × 107 OVCAR-3 cells suspended in a 1:1 mixture of PBS and Matrigel)[1]
-
Dosage:3, 10, 30, 100 mg/kg
-
Administration:p.o.; twice daily; 5 days
-
Result:Produced dose-dependent inhibition of tumor pRb S780 in CCNE1-high OVCAR-3 xenografts, reaching 79% inhibition at 100 mg/kg twice daily.
-
Animal Model:athymic nude (female, 4-6-week, 1 × 107 OVCAR-3 cells suspended in a 1:1 mixture of PBS and Matrigel)[1]
-
Dosage:3, 10, 30, 100 mg/kg (twice daily)
100 mg/kg (once daily) -
Administration:p.o.; twice daily or once daily; 24 days
-
Result:Reached 17% tumor growth inhibition at 3 mg/kg twice daily, 14% at 10 mg/kg twice daily, 65% at 30 mg/kg twice daily, 83% at 100 mg/kg twice daily, and 78% at 100 mg/kg once daily at study end.
- Kinase activity and phosphorylation assays
- Western Blot
- Flow cytometric DNA-content cell-cycle staining
- BrdU Incorporation Assay
- Patient-Derived Xenograft (PDX)
- Protocol for Cell Cycle
- Splenic/Portal-Vein Liver Metastasis Xenograft
- Protocol for Kinase activity and phosphorylation assays
- Subcutaneous Cell-Line-Derived Xenograft
- Orthotopic Cell-Line Xenograft
- Cell Viability Determination by MTT Colorimetric Assay
- Intraperitoneal/Peritoneal Dissemination Xenograft
Chemical Information
-
CAS No. 2602667-12-7
-
Molecular Weight 588.02
-
Formula C24H26ClF4N7O2S
-
SMILES
FC(C1=CN=C(NC2CCN(S(=O)(C)=O)CC2)N=C1C3=CN(C4=CC=C(CN5CCC5)C(F)=C4Cl)C=N3)(F)F
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
INCB127443 Related Classifications
HY-190774 Related Classifications
Powered by Bioz