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| Other Sizes |
Purity: ≥98%
| Targets |
CP-10 targets CDK6 (cyclin-dependent kinase 6) for degradation via the ubiquitin-proteasome system. For CDK6 degradation: DC50 ≈ 2.1 nM. For CDK4 degradation: DC50 ≈ 150-180 nM (50-80 fold higher). In vitro kinase inhibition activity for CDK4 or CDK6 is 10-25 fold weaker than palbociclib [1].
CP-10 targets CDK6, a cyclin-dependent kinase that forms complexes with cyclins D and is crucial for the G1 to S phase transition of the cell cycle. As a PROTAC, its mechanism of action is to induce the ubiquitination and subsequent proteasomal degradation of CDK6. It achieves this by simultaneously binding to CDK6 and the E3 ubiquitin ligase Cereblon, bringing them into close proximity and tagging CDK6 for destruction. |
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| ln Vitro |
CP-10 caused approximately 72% degradation of CDK6 at 10 nM and 89% degradation at 100 nM in human astroblastoma U251 cells. Compared to CDK6 (DC50), CDK4 is substantially less susceptible to CP-10's degradation. In both mantle cell thoracic cells (in Mino, IC50≈8 nM) and multiple myeloma cells MM.1S (IC50≈10 nM), CP-10 decreases cell viability [1]: 50–80 times][1].
CP-10 (10-100 nM) induces degradation of CDK6 in U251 cells: ~72% degradation at 10 nM, 89% at 100 nM. Time-lapse shows degradation begins at ~2 h, complete by 6 h. It is highly selective for CDK6 with minimal off-target effects (quantitative proteomics shows CDK6 as the most downregulated protein after 4 h treatment). CP-10 induces degradation of overexpressed CDK6 (in A-673 cells) and mutant forms D163G and S178P as efficiently as wild-type (though D163G slightly compromised). In palbociclib-resistant breast cancer cells (MCF-7 CDK6-amplified and FAT1 loss), CP-10 degrades CDK6 and CDK4 and inhibits proliferation. Control experiments: palbociclib, pomalidomide, or non-degrading controls CP-9 and CP-23 do not induce CDK6 degradation. Proteasome inhibitor carfilzomib and neddylation inhibitor MLN-4924 block CP-10-induced degradation. In vitro kinase assay shows CP-10 has weaker kinase inhibitory activity than palbociclib (10-25 fold) [1]. In vitro, CP-10 demonstrates remarkable CDK6 degradation activity with a DC₅₀ of 2.1 nM. In human glioblastoma U251 cells, CP-10 induces nearly 72% degradation of CDK6 at 10 nM and 89% at 100 nM, while the degradation of CDK4 is far weaker (50-80 fold), indicating its high selectivity. It also displays potent cell inhibition potential in mantle cell lymphoma cells (Mino, IC₅₀ ≈ 8 nM) and multiple myeloma cells (MM.1S, IC₅₀ ≈ 10 nM). |
| ln Vivo |
In vivo, CP-10, as a potent and selective CDK6 degrader, has the potential to inhibit the proliferation of various hematopoietic cancer cells, including those in multiple myeloma. Its ability to degrade mutated and overexpressed CDK6 makes it a valuable tool for studying CDK6-driven cancers. However, specific in vivo efficacy data in animal models, such as xenograft studies, are not extensively detailed in the provided literature.
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| Enzyme Assay |
In vitro kinase assay was performed to measure the kinase inhibitory activity of CP-10 against CDK4 and CDK6. The results showed that CP-10 had 10-25 fold weaker inhibitory activity compared to palbociclib. No detailed protocol for the kinase assay is provided in the paper [1].
In vitro degradation assays for CP-10 are typically performed using cell lines like human glioblastoma U251. Cells are treated with varying concentrations of CP-10 for a specified period (e.g., 4-24 hours). The level of CDK6 protein remaining is then quantified by Western blot analysis, and the DC₅₀ (the concentration required for 50% degradation) is calculated from the dose-response curve. The assay is often run in parallel with a control to assess the degradation of other proteins, like CDK4, to confirm selectivity. |
| Cell Assay |
CP-10 was tested in multiple cancer cell lines. Cells were treated with increasing concentrations of CP-10, and cell proliferation was measured by CCK-8 assay after 84 h. In MM.1S multiple myeloma cells, IC50 ≈ 10 nM (vs palbociclib IC50 ≈ 200 nM). In Mino mantle cell lymphoma cells, IC50 ≈ 8 nM (vs palbociclib IC50 ≈ 45 nM). In THP-1 and HL-60 leukemia cells, activities were comparable or weaker. In RPMI8226 multiple myeloma cells, CP-10 was far weaker than palbociclib. Non-degrading controls CP-9 and CP-23 barely inhibited proliferation. Immunoblots were performed to detect CDK4, CDK6, and phospho-Rb (S780) levels. For degradation assays, U251 cells were treated with CP-10 at indicated concentrations for 24 h, then lysates were immunoblotted with anti-CDK6, anti-CDK4, and anti-β-tubulin antibodies. DC50 values were calculated from densitometry. For time-lapse, cells were treated with 100 nM CP-10 and harvested at 0, 2, 4, 6, 12, 24 h. For selectivity, U251 cells were treated with 500 nM CP-10 or DMSO for 4 h, then quantitative proteomic analysis was performed. For mutant degradation, MCF-7 cells stably expressing FLAG-tagged CDK6 WT, D163G, or S178P were treated with 50 nM or 200 nM CP-10 for 24 h, then immunoblotted with anti-FLAG. For overexpression model, A-673 cells (low endogenous CDK6) were transduced with CDK6 via lentivirus, then treated with DMSO or 200 nM CP-10 for 24 h. For resistant cell lines, MCF-7 CDK6-amplified and MCF-7 FAT1 CRISPR cells were treated with 200 nM CP-10 for 24 h [1].
In vitro cell-based assays for CP-10 are used to assess its anti-proliferative effects. Cancer cell lines, such as Mino (mantle cell lymphoma) and MM.1S (multiple myeloma), are cultured and treated with CP-10 at various concentrations for 48-72 hours. Cell viability and proliferation are then measured using standard assays like MTT, CellTiter-Glo, or by counting viable cells, allowing for the determination of the IC₅₀. |
| Animal Protocol |
In vivo animal studies for CP-10 would typically involve using mouse xenograft models. Immunodeficient mice are injected with cancer cells (e.g., MM.1S or Mino) to establish tumors. Once tumors reach a certain size, mice are treated with CP-10, often via intraperitoneal (IP) or intravenous (IV) injection. Tumor growth is measured over time to assess the compound's efficacy. Pharmacodynamic studies would also be performed to confirm CDK6 degradation in tumor tissue.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic properties of CP-10, such as half-life and oral bioavailability, are not detailed in the available literature. As a PROTAC with a high molecular weight (871.94), it is likely to have poor oral bioavailability and is typically administered via injection in research settings. It is soluble in DMSO at 200 mg/mL, suggesting it can be formulated for in vivo administration.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for CP-10 are not available in the provided text. As a research compound, it is intended for laboratory use only and is not for human therapeutic use. Safety precautions should be followed when handling this compound. The purity of the compound is typically ≥95%.
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| References | |
| Additional Infomation |
CP-10 is a PROTAC degrader targeting CDK6, derived from palbociclib and pomalidomide. It preferentially degrades CDK6 over CDK4 despite similar binding affinity of the parent inhibitor. The selectivity is attributed to a more stable ternary complex formation (docking scores: CP-10 with CDK6 -10.24, with CDK4 -7.31) and potentially more lysine residues on CDK6 (18 vs 11). CP-10 overcomes CDK6 inhibitor resistance mechanisms including CDK6 overexpression (gene amplification or FAT1 loss) and point mutations (D163G, S178P) that reduce palbociclib binding. It shows potent antiproliferative activity in hematopoietic cancers, especially multiple myeloma, and represents a promising therapeutic strategy for CDK6-dependent cancers [1].
CP-10 is a PROTAC (PROteolysis TArgeting Chimera) that acts as a highly selective and potent degrader of CDK6. It is a valuable tool for studying CDK6 biology and for validating CDK6 as a therapeutic target in cancer. This product is for research use only. |
| Molecular Formula |
C10H13CL9
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|---|---|
| Molecular Weight |
452.2872
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| Exact Mass |
871.387
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| CAS # |
2366268-80-4
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| PubChem CID |
138911323
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
1.8
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
16
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| Rotatable Bond Count |
15
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| Heavy Atom Count |
64
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| Complexity |
1810
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC([H])(C([H])(C([H])(C([H])(C([H])([H])Cl)Cl)Cl)Cl)C([H])(C([H])(C([H])(C([H])(C([H])([H])[H])Cl)Cl)Cl)Cl
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| InChi Key |
PACRWHUPEPCFHX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C44H49N13O7/c1-26-32-23-47-44(50-39(32)56(29-6-3-4-7-29)42(62)37(26)27(2)58)48-35-12-10-30(22-46-35)54-17-15-53(16-18-54)24-28-25-55(52-51-28)19-21-64-20-14-45-33-9-5-8-31-38(33)43(63)57(41(31)61)34-11-13-36(59)49-40(34)60/h5,8-10,12,22-23,25,29,34,45H,3-4,6-7,11,13-21,24H2,1-2H3,(H,49,59,60)(H,46,47,48,50)
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| Chemical Name |
4-[2-[2-[4-[[4-[6-[(6-acetyl-8-cyclopentyl-5-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]pyridin-3-yl]piperazin-1-yl]methyl]triazol-1-yl]ethoxy]ethylamino]-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione
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| Synonyms |
CP-10; CP 10; CP10
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : ~200 mg/mL (~229.37 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2110 mL | 11.0549 mL | 22.1097 mL | |
| 5 mM | 0.4422 mL | 2.2110 mL | 4.4219 mL | |
| 10 mM | 0.2211 mL | 1.1055 mL | 2.2110 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.
Products are for research use only; We do not sell to patients
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