PROTAC CDK9 degrader-11
PROTAC CDK9 degrader-11 is an orally active, selective CDK9 PROTAC degrader with a DC50 of 1.09 nM. PROTAC CDK9 degrader-11 recruits CRBN to form a ternary complex and degrades CDK9 via the ubiquitin-proteasome pathway, thereby inhibiting RNA polymerase II phosphorylation and downregulating the expression of anti-apoptotic and pro-oncogenic genes, ultimately inducing apoptosis. PROTAC CDK9 degrader-11 is suitable for research on small-cell lung cancer (SCLC).
(Pink: CDK9 ligand (HY-170979); Blue: Cereblon ligand (HY-W247437); Black: linker).
For research use only. We do not sell to patients.
- CAS No.: 3039540-19-4
- Formula: C39H48Cl2N10O5
- Molecular Weight:807.77
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Storage:
-20°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
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
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
CDK9 1.09 nM (DC50) |
PARP-1 |
Caspase 3 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| NCI-H69 | IC50 |
1.027 mM
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Significantly inhibits cell viability.
Significantly inhibits cell viability.
|
39895086 |
| NCI-H446 | IC50 |
1.008 nM
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Significantly inhibits cell viability.
Significantly inhibits cell viability.
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39895086 |
| BEAS-2B | IC50 |
412.8 nM
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Does not affect cell viability.
Does not affect cell viability.
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39895086 |
| L02 | IC50 |
69.94 nM
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Does not affect cell viability.
Does not affect cell viability.
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39895086 |
| HEK-293T | IC50 |
95.47 nM
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Does not affect cell viability.
Does not affect cell viability.
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39895086 |
In Vitro
PROTAC CDK9 degrader-11 (Compound C3) (0.5-10.0 nM; 8 h) induces the degradation of CDK9 protein in a concentration-dependent manner in NCI-H69 and NCI-H446 cells[1].
PROTAC CDK9 degrader-11 (10 nM; 0.5-12 h) induces the time-dependent degradation of CDK9 protein and promotes CDK9 ubiquitination in NCI-H69 and NCI-H446 cells[1].
PROTAC CDK9 degrader-11 (0.5-10.0 nM; 24 h) inhibits RNA Pol II phosphorylation (at Ser2 and Ser5 sites) and downregulates c-Myc protein expression in NCI-H69 cells[1].
PROTAC CDK9 degrader-11 (1 pM-10 μM; 72 h) significantly inhibits cell viability in NCI-H69 (IC50 = 1.027 nM), NCI-H146, NCI-H446 (IC50 = 1.008 nM), NCI-H524, and DMS114 cells, while showing lower cytotoxicity in normal cells such as MCF10A (IC50 = 126.3 nM), Beas-2b (IC50 = 412.8 nM), LO2 (IC50 = 69.94 nM), and 293T (IC50 = 95.47 nM)[1].
PROTAC CDK9 degrader-11 (2-4 nM; 8-21 days) inhibits colony formation in NCI-H69, NCI-H446, and DMS114 cells[1].
PROTAC CDK9 degrader-11 (0.5-4 nM; 36 h) induces cell cycle arrest at the G0/G1 phase and apoptosis in NCI-H69 and NCI-H446 cells[1].
PROTAC CDK9 degrader-11 (0.5-5.0 nM; 36 h) downregulates the expression of MCL-1 and BCL-2 and upregulates the expression of Cleaved-PARP and Cleaved-Caspase-3 in NCI-H69 cells[1].
PROTAC CDK9 degrader-11 (2-4 nM; 48 h) inhibits cell invasion in DMS114 and DMS53 cells[1].
PROTAC CDK9 degrader-11 (0.3-30 μM; 18 h) demonstrates a low risk of cardiotoxicity (IC50 > 30 μM) in an in vitro hERG binding assay using HEK-293 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:NCI-H69, NCI-H446
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Concentration:0.5, 1.0, 2.5, 5.0, 7.5, 10.0 nM
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Incubation Time:8 h
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Result:Decreased CDK9 protein levels in a dose-dependent manner.
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Cell Line:NCI-H69, NCI-H446
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Concentration:10 nM
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Incubation Time:0.5, 1, 3, 6, 12 h
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Result:Decreased CDK9 protein levels in a time-dependent manner.
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Cell Line:NCI-H69, NCI-H446
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Concentration:0.5, 1.0, 2.5, 5.0, 7.5, 10.0 nM
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Incubation Time:3 h
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Result:Significantly increased the ubiquitination levels of CDK9 protein.
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Cell Line:NCI-H69
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Concentration:0.5, 1.0, 2.5, 5.0, 7.5, 10.0 nM
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Incubation Time:24 h
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Result:Decreased the phosphorylation levels of RNA Pol II (Ser2 and Ser5) in a dose-dependent manner.
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Cell Line:NCI-H69
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Concentration:2.5, 5, 10 nM
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Incubation Time:24 h
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Result:Decreased the expression of c-Myc protein in a dose-dependent manner.
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Cell Line:NCI-H69, NCI-H146, NCI-H446, NCI-H524, DMS114
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Concentration:1 pM, 10 pM, 100 pM, 1 nM, 10 nM, 100 nM, 1 μM, 10 μM
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Incubation Time:72 h
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Result:Significantly decreased cell viability.
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Cell Line:NCI-H69, NCI-H446, DMS114
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Concentration:2, 4 nM
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Incubation Time:8 to 21 days
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Result:Significantly decreased the number of malignant colonies formed.
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Cell Line:NCI-H69, NCI-H446
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Concentration:0.5, 1, 2, 4 nM
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Incubation Time:36 h
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Result:Increased the proportion of cells in the G1 phase in a dose-dependent manner.
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Cell Line:NCI-H69, NCI-H446
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Concentration:1, 2, 4 nM
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Incubation Time:36 h
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Result:Increased cell apoptosis rates in a dose-dependent manner.
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Cell Line:NCI-H69
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Concentration:0.5, 1.0, 2.5, 5.0 nM
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Incubation Time:36 h
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Result:Upregulated the expression of pro-apoptotic proteins (Cleaved-PARP, Cleaved-Caspase-3) and downregulated anti-apoptotic proteins (MCL-1, BCL-2).
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Cell Line:DMS114, DMS53
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Concentration:2, 4 nM
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Incubation Time:48 h
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Result:Significantly decreased the number of invading cells migrating through the upper chamber.
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Cell Line:MCF10A, Beas-2b, LO2, 293T
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Concentration:100 nM, 1 μM, 10 μM, 100 μM
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Incubation Time:72 h
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Result:Normal cell viability was less affected, exhibiting low cytotoxicity.
Parmacokinetics
| Species | Dose | Route | T1/2 | Cmax | AUC0-24 | AUC0-∞ | F |
|---|---|---|---|---|---|---|---|
| Mice | 25 mg/kg | p.o. | 4.7 h | 277 ng/mL | 951 ng·h/mL | 977 ng·h/mL | 6.8 % |
| Mice | 5 mg/kg | i.v. | 8.2 h | 2603 ng/mL | 2660 ng·h/mL | 2857 ng·h/mL | / |
| Rat | 25 mg/kg | p.o. | 5.4 h | 179 ng/mL | 714 ng·h/mL | 893 ng·h/mL | 6.5 % |
| Rat | 5 mg/kg | i.v. | 2.8 h | 2003 ng/mL | 2179 ng·h/mL | 2331 ng·h/mL | / |
In Vivo
PROTAC CDK9 degrader-11 (12.5 mg/kg or 25.0 mg/kg; p.o.; once daily; 19 days) significantly reduced systemic metastasis and overall tumor burden in a BALB/c nude mouse model with systemic metastasis induced by tail vein injection of NCI-H446-Luc-GFP cells[1].
PROTAC CDK9 degrader-11 (12.5 mg/kg or 25.0 mg/kg; p.o.; once daily; 7 days) demonstrated significant inhibition of primary tumor growth in a small-cell lung cancer Mini-PDX model[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 mice (female, 6-week-old) were subcutaneously injected with 5 x 10 6 NCI-H446 cells[1]
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Dosage:12.5 mg/kg and 25.0 mg/kg
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Administration:p.o.; once daily; for 14 days
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Result:Significantly decreased tumor volume and weight, exhibiting dose-dependent tumor growth inhibitory activity.
Animal body weight remained stable throughout the administration period, and no obvious toxic side effects were observed.
Significantly decreased the expression levels of CDK9 and the proliferation marker Ki-67, while the expression level of the apoptosis marker Cleaved-caspase-3 significantly increased.
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Animal Model:BALB/c nude mice (6-week-old) were injected via the tail vein with 5 x 10 6 NCI-H446-Luc-GFP cells[1]
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Dosage:12.5 mg/kg and 25.0 mg/kg
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Administration:p.o.; once daily; for 19 days
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Result:Significantly attenuated the fluorescence signal intensity in vivo, as demonstrated by in vivo imaging.
Significantly decreased systemic metastasis and overall tumor burden.
There was no significant difference in body weight changes among the groups of mice.
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Animal Model:BALB/c nude mice (four-week-old, 15-20 g) were used to establish the model by subcutaneously implanting capsules with primary small-cell lung cancer (three capsules per mouse; capsules were washed with HBSS) [1]
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Dosage:12.5 mg/kg and 25.0 mg/kg
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Administration:p.o.; once daily; for 7 days
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Result:Significantly reduced the relative fluorescence units (RFU) within capsules containing primary samples.
Demonstrated significant tumor growth inhibition across all tested sample models.
Chemical Information
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CAS No. 3039540-19-4
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Appearance Solid
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Molecular Weight 807.77
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Formula C39H48Cl2N10O5
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Color White to off-white
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SMILES
O=C(NC1=CNN=C1C(NC2CCN(CC2)C(CN3CCC(CC3)CN4CCN(CC4)C5=CC(NC6C(NC(CC6)=O)=O)=CC=C5)=O)=O)C7=C(C=CC=C7Cl)Cl
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
-20°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (123.80 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (3.09 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (3.09 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
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Data Sheet (288 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.2380 mL | 6.1899 mL | 12.3798 mL | 30.9494 mL |
| 5 mM | 0.2476 mL | 1.2380 mL | 2.4760 mL | 6.1899 mL | |
| 10 mM | 0.1238 mL | 0.6190 mL | 1.2380 mL | 3.0949 mL | |
| 15 mM | 0.0825 mL | 0.4127 mL | 0.8253 mL | 2.0633 mL | |
| 20 mM | 0.0619 mL | 0.3095 mL | 0.6190 mL | 1.5475 mL | |
| 25 mM | 0.0495 mL | 0.2476 mL | 0.4952 mL | 1.2380 mL | |
| 30 mM | 0.0413 mL | 0.2063 mL | 0.4127 mL | 1.0316 mL | |
| 40 mM | 0.0309 mL | 0.1547 mL | 0.3095 mL | 0.7737 mL | |
| 50 mM | 0.0248 mL | 0.1238 mL | 0.2476 mL | 0.6190 mL | |
| 60 mM | 0.0206 mL | 0.1032 mL | 0.2063 mL | 0.5158 mL | |
| 80 mM | 0.0155 mL | 0.0774 mL | 0.1547 mL | 0.3869 mL | |
| 100 mM | 0.0124 mL | 0.0619 mL | 0.1238 mL | 0.3095 mL |
PROTAC CDK9 degrader-11 Related Classifications
HY-170978 Related Classifications
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