CDK9-IN-54
CDK9-IN-54 is an orally active and selective CDK9 inhibitor (IC50 = 0.9 nM), with IC50 values of 100.3 nM, 45.7 nM, 114.9 nM, 92.1 nM, 5.2 nM, and 9.5 nM against CDK1, CDK2, CDK4, CDK7, CLK1, and ERK7, respectively. CDK9-IN-54 directly binds CDK9/cyclin T1 in live cells and downregulates RNA polymerase II Ser2 phosphorylation. CDK9-IN-54 inhibits tumor cell proliferation, migration, and invasion, induces DNA damage, cell cycle arrest, and apoptosis (apoptosis), and downregulates Mcl-1 and c-Myc. CDK9-IN-54 inhibits the growth of hepatocellular carcinoma xenograft tumors. CDK9-IN-54 can be used for research on hepatocellular carcinoma[1].
For research use only. We do not sell to patients.
- CAS No.: 3145822-23-4
- Formula: C25H27FN6O2
- Molecular Weight:462.52
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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]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
All DNA/RNA Synthesis Isoforms
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Biological Activity
Description
IC50 & Target
[1]|
CDK9 0.9 nM (IC50) |
CDK1 100.3 nM (IC50) |
CDK4 114.9 nM (IC50) |
CDK7 92.1 nM (IC50) |
CDK2 45.7 nM (IC50) |
ERK7 9.5 nM (IC50) |
CLK1 5.2 nM (IC50) |
Mcl-1 |
RNA Polymerase |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK-293T | IC50 |
16.41 nM
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CDK9/Cyclin T1 target engagement in live HEK293T cells by NanoBRET assay.
CDK9/Cyclin T1 target engagement in live HEK293T cells by NanoBRET assay.
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acs.jmedchem.6c01374 |
| Huh-7 | IC50 |
0.044 μM
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Antiproliferative activity against human Huh-7 cells.
Antiproliferative activity against human Huh-7 cells.
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acs.jmedchem.6c01374 |
| HepG2 | IC50 |
0.028 μM
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Antiproliferative activity against human HepG2 cells.
Antiproliferative activity against human HepG2 cells.
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acs.jmedchem.6c01374 |
In Vitro
CDK9-IN-54 causes moderate CYP3A4 inhibition, exhibits moderate Caco-2 permeability with a Papp A→B of 6.41 × 10-6 cm/s, shows a high plasma protein binding rate of 92.2%, and has moderate stability in human liver microsomes but is rapidly metabolized by rat liver microsomes[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Huh-7 cells
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Concentration:50, 100, 200 nM
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Incubation Time:12 h
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Result:Suppressed migration and invasion of Huh-7 cells.
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Cell Line:Huh-7 cells
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Concentration:100, 200, 500 nM
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Incubation Time:12 h
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Result:Induced dose-dependent G2/M-phase accumulation in Huh-7 cells.
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Cell Line:Huh-7 cells
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Concentration:100, 200, 500 nM
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Incubation Time:12 h
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Result:Induced concentration-dependent apoptosis in Huh-7 cells.
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Cell Line:Huh-7 cells
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Concentration:50, 100, 200 nM
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Incubation Time:12 h
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Result:Downregulated p-RNAPII-Ser2 and reduced Mcl-1 and c-Myc protein levels.
At 200 nM, Mcl-1 was reduced by approximately 90% and c-Myc by approximately 60%.
Parmacokinetics
| Species | Dose | Route | AUC0-t | T1/2 | Vz |
|---|---|---|---|---|---|
| Rat[1] | 5 mg/kg | i.v. | 2191.6 μg/L·h | 0.73 h | 2.4 L/kg |
In Vivo
CDK9-IN-54 (10-20 mg/kg; i.v.; every other day; approximately 2 weeks) significantly inhibits the growth of Huh-7 xenograft tumors in BALB/c nude mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude (male, 18-22 g, 1×107 HepG2 cells)[1]
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Dosage:10 mg/kg; 20 mg/kg
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Administration:i.v.; every other day; approximately 2 weeks
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Result:Suppressed HepG2 xenograft tumor growth in BALB/c nude mice, achieving TGI of 63.2% at 10 mg/kg and 77.6% at 20 mg/kg and reducing endpoint tumor weight.
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Animal Model:BALB/c nude (male, 18-22 g, 1×107 Huh-7 cells)[1]
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Dosage:10 mg/kg; 20 mg/kg
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Administration:i.v.; every other day; approximately 2 weeks
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Result:Suppressed Huh-7 xenograft tumor growth in BALB/c nude mice, achieving TGI of 52.7% at 10 mg/kg and 81.7% at 20 mg/kg and reducing endpoint tumor weight, Mcl-1, c-Myc, and Ki67.
- Cell migration
- Somatic Cell Culture
- Liver Cancer Modeling
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Flow cytometric DNA-content cell-cycle staining
- Apoptosis Solutions
- Cell invasion
- MTT Cell Proliferation Assay
- Genotoxicity/Mutagenicity Study
- Western Blot
- Annexin V plus membrane-impermeant dye apoptosis staining
- BrdU Incorporation Assay
- CFSE Dye Dilution Proliferation Assay
- Dye-dilution cell tracking and proliferation staining
- CCK-8/WST-8 Cell Proliferation Assay
- Protocol for Cell Cycle
- Cell Counting-Based Growth Curve Assay
- Colony Formation (Clonogenic) Assay
- Cell Viability Determination by MTT Colorimetric Assay
- Kinase activity and phosphorylation assays
- EdU Incorporation Assay (Click Chemistry-Based DNA Synthesis Measurement)
- Ki-67 Immunostaining Proliferation Assay
- PCNA Immunodetection Proliferation Assay
- Protocol for Cell Counting and Cell Density Analysis
- Patient-Derived Xenograft (PDX)
- Splenic/Portal-Vein Liver Metastasis Xenograft
- Protocol for Kinase activity and phosphorylation assays
- Subcutaneous Cell-Line-Derived Xenograft
- Orthotopic Cell-Line Xenograft
- Intraperitoneal/Peritoneal Dissemination Xenograft
Chemical Information
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CAS No. 3145822-23-4
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Molecular Weight 462.52
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Formula C25H27FN6O2
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SMILES
FC(C=N1)=C(C2=CN(C(C)C)C(C=C2)=O)N=C1NC3=CC=C4C(NC=C4CN5CCOCC5)=C3
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Shipping
Room temperature in continental US; may vary elsewhere.
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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)
CDK9-IN-54 Related Classifications
HY-191430 Related Classifications
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