CDK9 degrader-1
CDK9 degrader-1 is a HyT-type CDK9 degrader that selectively induces protein degradation by recruiting ATG101 (with a DC50 of 0.4073 μM in HCT116 cells). CDK9 degrader-1 recruits ATG101 to initiate the autophagy-lysosome pathway, forming LC3-containing autophagosomes that fuse with lysosomes to degrade CDK9. CDK9 degrader-1 mediates the degradation of Cyclin T1 via the same autophagy-lysosome pathway. CDK9 degrader-1 induces downstream phenotypic effects associated with CDK9 degradation. CDK9 degrader-1 can be used in the research of colorectal cancer (Blue: hydrophobic group; Pnk: CDK9 ligand (HY-50940); Black: linker (HY-N0420)).
For research use only. We do not sell to patients.
- Formula: C32H34Cl2N6O4
- Molecular Weight:637.56
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Protocols
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- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
CDK9 0.4073 μM (DC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HCT-116 | GI50 |
0.72 μM
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Inhibition of cell viability against human HCT116 colon cancer cells assessed by CCK8 assay after 48 h incubation with the reagent, followed by 4 h incubation with CCK8 solution before absorbance measurement at 450 nm.
Inhibition of cell viability against human HCT116 colon cancer cells assessed by CCK8 assay after 48 h incubation with the reagent, followed by 4 h incubation with CCK8 solution before absorbance measurement at 450 nm.
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40487652 |
| HCT-116 | DC50 |
0.4073 μM
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Dose-dependent degradation of CDK9 protein in human HCT116 colon cancer cells assessed by Western blot analysis.
Dose-dependent degradation of CDK9 protein in human HCT116 colon cancer cells assessed by Western blot analysis.
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40487652 |
| HCT-116 | DC50 |
1.215 μM
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Dose-dependent degradation of Cyclin T1 protein in human HCT116 colon cancer cells assessed by Western blot analysis.
Dose-dependent degradation of Cyclin T1 protein in human HCT116 colon cancer cells assessed by Western blot analysis.
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40487652 |
In Vitro
CDK9 degrader-1 (AZ-9) (48 h) potently inhibits HCT116 cell viability with a GI50 of 0.72 μM, an effect dependent on CDK9 degradation[1].
CDK9 degrader-1 (0.1875-12 μM) dose-dependently degrades CDK9 with a DC50 of 0.4073 μM and Cyclin T1 with a DC50 of 1.215 μM in HCT116 cells[1].
CDK9 degrader-1 (1 μM; 0-24 h) induces time-dependent degradation of CDK9 in HCT116 cells, with significant effects starting at 8 h, while Cyclin T1 degradation is not significant after 24 h[1].
CDK9 degrader-1 (3 μM; 24 h pretreatment, followed by 0-24 h in drug-free medium) induces persistent degradation of CDK9 in HCT116 cells, with effects lasting up to 24 h after wash-out[1].
CDK9 degrader-1 (0.75-12 μM) selectively degrades CDK9 and Cyclin T1 without affecting CDK2, CDK4, or CDK6 in HCT116, HT-29, DLD-1, RKO, and MOLM-13 cells[1].
CDK9 degrader-1 (1-6 μM; 24-48 h) downregulates CDK9 downstream signaling in HCT116 cells, reducing anti-apoptotic protein levels and inducing caspase 3-mediated apoptosis[1].
CDK9 degrader-1 (1 μM; 8 h pretreatment, 48 h incubation) induces degradation of CDK9 and Cyclin T1 in HCT116 cells via the autophagy-lysosome pathway[1].
CDK9 degrader-1 (1 μM; 48 h) promotes degradation of CDK9 and Cyclin T1 in HCT116 cells by enhancing the interaction between CDK9 and ATG101, which is essential for the autophagy-lysosome pathway-mediated degradation[1].
CDK9 degrader-1 (1-3 μM; 24-48 h) induces autophagy-lysosome pathway activation in HCT116 cells, increasing autophagosome formation and lysosome fusion to mediate CDK9 degradation[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:HCT116 colon cancer cells
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Concentration:1 μM
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Incubation Time:0-24 h
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Result:Degraded CDK9 in a time-dependent manner, with significant degradation observed starting at 8 h.
Did not cause a significant decrease in Cyclin T1 levels after 24 h of exposure.
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Cell Line:HCT116 colon cancer cells
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Concentration:1 μM
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Incubation Time:0-8 h
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Result:Reduced CDK9 content when combined with CHX, while CHX alone did not reduce CDK9 levels within 8 h.
Confirmed chemically induced CDK9 degradation rather than altered protein half-life.
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Cell Line:HCT116 colon cancer cells
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Concentration:3 μM
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Incubation Time:24 h pretreatment, followed by 0-24 h in drug-free medium
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Result:Maintained a long-lasting degradation effect on CDK9 after drug removal, with reduced CDK9 levels persisting for up to 24 h in drug-free medium.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nu/nu (6-week-old female; colorectal cancer xenograft model via HCT116 cell injection)[1]
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Dosage:50 mg/kg; 20 mg/kg
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Administration:p.o.; daily; 15 days; i.p.; daily; 15 days
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Result:Reduced tumor volume and weight.
Degraded CDK9 and Cyclin T1 in tumor tissues, with no significant effect on CDK2, CDK4, or CDK6.
Inhibited phosphorylation of RNA polymerase II at Ser 2.
Reduced mRNA and protein levels of Mcl-1, c-Myc, and Bcl-2.
Induced cleavage of caspase 3 and PARP.
Lowered the number of Ki67-positive cells in tumors compared to vehicle and AT7519-treated groups.
Caused no obvious toxicity in heart, liver, spleen, lungs, or kidneys via H&E staining.
Caused no significant body weight loss.
Chemical Information
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Molecular Weight 637.56
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Formula C32H34Cl2N6O4
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SMILES
ClC1=C(C(NC2=CNN=C2C(NC3CCN(C(CCC(NC4=C(CCC5)C5=CC6=C4CCC6)=O)=O)CC3)=O)=O)C(Cl)=CC=C1
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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.
Protocols
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Autophagy
Autophagy is a process in which eukaryotic cells use lysosomes to degrade their own cytoplasmic proteins and damaged organelles under the regulation of autophagy related gene (Atg). Microtubule-associated proteins light chain 3 (LC3) is recognized as autophagy marker, which transfers from cytoplasmic LC3 (LC3-I) to membrane type (LC3-II). LC3-II/I ratio could be detected by Western Blot and fluorescence microscopy.
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Lysosome and acidic-vesicle live-cell staining
Lysosome and acidic-vesicle live-cell staining detects acidic intracellular compartments by using membrane-permeant acidotropic probes that accumulate in low-pH vesicles, including lysosomes, late endosomes, autolysosomes, and acidic phagosomes. LysoTracker staining is commonly used as an intensity-based readout of acidic lysosomal compartment abundance or enlargement, while acridine orange produces green fluorescence in less concentrated compartments and red fluorescence after concentration-dependent accumulation in acidic vesicular organelles. Loss or reduction of acridine-orange red signal can be used as a readout of lysosomal membrane permeabilization or reduced acidic-vesicle integrity. This protocol is designed for live cultured cells and can be adapted for fluorescence microscopy, high-content imaging, plate-reader readout, or flow cytometry when the selected literature supports the readout. Because these dyes report acidotropic accumulation rather than lysosome identity alone,
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Macroautophagy Solutions
Macroautophagy is a conserved lysosome-dependent degradation pathway in which cytoplasmic material is sequestered into double-membrane autophagosomes and delivered to lysosomes for degradation and recycling. The pathway supports cellular homeostasis during nutrient limitation, organelle stress, protein-aggregate accumulation, infection, differentiation, and tissue remodeling by coupling cargo sequestration, autophagosome maturation, lysosomal fusion, and degradation of cargo-derived macromolecules. The core molecular sequence includes initiation by nutrient- and stress-regulated autophagy machinery, autophagosome nucleation, LC3/ATG8-family conjugation to autophagosomal membranes, cargo selection through receptors such as SQSTM1/p62, autophagosome-lysosome fusion, and lysosomal degradation. LC3 was identified as a mammalian homolog of yeast Atg8 that localizes to autophagosomal membranes after processing, and p62/SQSTM1 was shown to connect ubiquitinated cargo with autophagic degradati
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
CDK9 degrader-1 Related Classifications
HY-176451 Related Classifications
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