| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
Cyclin-Dependent Kinase 9 (CDK9). PROTAC CDK9 degrader-7 binds simultaneously to CDK9 and the E3 ubiquitin ligase (specifically utilizing the CRBN-ligand). This ternary complex induces the ubiquitination of CDK9, marking it for degradation by the proteasome. This event effectively depletes CDK9 protein from the cell. CDK9 is a key regulator of transcriptional elongation (via phosphorylation of RNA Polymerase II). Its degradation selectively disrupts the transcription of short-lived anti-apoptotic proteins like MCL-1.
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| ln Vitro |
In Molm-13 cells, PROTAC CDK9 degrader-7 (compound 15f) degrades CDK9 with an IC50 of 40 nM, demonstrating maximal efficacy [1].
In Molm-13 and MV411 leukemia cells, PROTAC CDK9 degrader-7 demonstrates potent CDK9 degradation. The IC₅0 for CDK9 degradation in Molm-13 cells is 40 nM, and it achieves maximal efficacy at higher concentrations. In MV411 cells, the compound (0.01-5 microM for 6 hours) dramatically diminishes the protein level of MCL-2 and completely degrades CDK9 at concentrations as low as 0.1 microM. This confirms its highly potent and selective degradation capacity, surpassing traditional inhibition paradigms. |
| ln Vivo |
Specific in vivo animal efficacy data for this exact degrader was not found in the search results. However, as a PROTAC targeting CDK9, it is expected to show significant anti-tumor activity in mouse xenograft models of acute myeloid leukemia (AML) or other hematologic malignancies. A typical study would involve intravenous or intraperitoneal administration of the compound, followed by measurement of tumor regression, survival benefit, and pharmacodynamic confirmation of CDK9 knockdown in harvested tumor tissue (via Western blot).
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| Enzyme Assay |
No specific non-cell assay protocol is relevant for a PROTAC as it requires the ternary complex. Activity is assessed via a TR-FRET (Time-Resolved Fluorescence Resonance Energy Transfer) ternary complex formation assay. Recombinant biotin-labeled CDK9, GST-labeled CRBN (E3 ligase), a chemical crosslinker or PROTAC compound, and an anti-GST terbium donor and streptavidin acceptor beads are mixed. If the PROTAC engages both proteins, a signal is produced (excitation at 340 nm, emission at 520/620 nm). This measures binding affinity in a cell-free context.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: MV411 cells Tested Concentrations: 0.01 μM, 0.05 μM, 0.1 μM, 0.5 μM, 1 μM, 5 μM Incubation Duration: 6 h Experimental Results: Dramatically diminished the protein level of MCL2, and almostly and competely degraded CKD9 at low concentration as 0.1 μM. MV411 or Molm-13 human leukemia cells are seeded in 6-well plates and treated with varying concentrations of PROTAC CDK9 degrader-7 (0.01, 0.05, 0.1, 0.5, 1, 5 microM) for 6 hours. Cells are then harvested, lysed, and protein concentration is normalized. Whole cell lysates are subjected to SDS-PAGE and Western blotting using antibodies specific for CDK9, MCL-1, and beta-actin as a loading control. Signal intensity is quantified to calculate the DC₅0 (concentration for 50% degradation). A typical protocol uses a NOD/SCID mouse xenograft model. 5 × 10⁶ K562-Luc (engineered to express luciferase) cells are injected subcutaneously into the flank. When tumors reach ~150 mm3, mice are randomized into treatment groups (n=6-8). PROTAC CDK9 degrader-7 is dissolved in a formulation of 10% DMSO and 90% corn oil, then administered intraperitoneally at doses of 5, 15, and 45 mg/kg. Treatment is given daily or as per the study design. Tumor progression is monitored by bioluminescence imaging or caliper measurement. At endpoint, tumors are harvested for analysis of CDK9 levels. |
| ADME/Pharmacokinetics |
No data was found for this specific compound. As a PROTAC (molecular weight ~893.81), it is significantly larger than traditional small molecules. Therefore, its oral bioavailability is likely to be low. It is typically formulated in DMSO and corn oil for intraperitoneal (IP) administration to ensure systemic exposure. It is unstable in solution and should be prepared fresh. The half-life in mice is likely short, but the pharmacodynamic effect (protein degradation) may persist longer than the compound‘s presence in the plasma.
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| Toxicity/Toxicokinetics |
Dedicated toxicology studies for this research compound are not available. However, the mechanism of CDK9 degradation can lead to the loss of MCL-1, a critical survival protein. This could potentially cause on-target toxicities in tissues with high cellular turnover, such as the bone marrow, gastrointestinal tract, and lymphoid organs. High doses might induce thrombocytopenia, neutropenia, and gastrointestinal distress. A wide therapeutic window is required to avoid such risks.
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| References |
[1]. Tokarski RJ 2nd, et al. Bifunctional degraders of cyclin dependent kinase 9 (CDK9): Probing the relationship between linker length, properties, and selective protein degradation. Eur J Med Chem. 2023 Jun 5;254:115342.
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| Additional Infomation |
PROTAC CDK9 degrader-7 is a cutting-edge research tool for chemical biology and early drug discovery. It is not a clinically approved drug. This technology has not yet entered Phase I clinical trials, but PROTACs represent a promising new therapeutic modality. This compound is useful for validating CDK9 as a target for therapeutic intervention in cancer and for studying the pharmacology of protein degraders versus enzyme inhibitors.
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| Molecular Formula |
C43H50CL2N8O9
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|---|---|
| Molecular Weight |
893.81
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| Exact Mass |
892.308
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| CAS # |
2935587-90-7
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| PubChem CID |
168355536
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
20
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| Heavy Atom Count |
62
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| Complexity |
1620
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C(=CC=C3)OCC(=O)NCCCCCCCCCCCC(=O)N4CCC(CC4)NC(=O)C5=C(C=NN5)NC(=O)C6=C(C=CC=C6Cl)Cl
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| InChi Key |
VOTFYHWCGUFSOV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C43H50Cl2N8O9/c44-28-13-11-14-29(45)37(28)40(58)49-30-24-47-51-38(30)41(59)48-26-19-22-52(23-20-26)35(56)16-8-6-4-2-1-3-5-7-9-21-46-34(55)25-62-32-15-10-12-27-36(32)43(61)53(42(27)60)31-17-18-33(54)50-39(31)57/h10-15,24,26,31H,1-9,16-23,25H2,(H,46,55)(H,47,51)(H,48,59)(H,49,58)(H,50,54,57)
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| Chemical Name |
4-[(2,6-dichlorobenzoyl)amino]-N-[1-[12-[[2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyacetyl]amino]dodecanoyl]piperidin-4-yl]-1H-pyrazole-5-carboxamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~111.88 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1188 mL | 5.5940 mL | 11.1881 mL | |
| 5 mM | 0.2238 mL | 1.1188 mL | 2.2376 mL | |
| 10 mM | 0.1119 mL | 0.5594 mL | 1.1188 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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