| Size | Price | Stock | Qty |
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| 1mg |
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| Targets |
The target is CDK4 (Cyclin-dependent kinase 4). CDK4 forms a complex with cyclin D to phosphorylate the retinoblastoma (Rb) protein, a key step in the G1-to-S phase cell cycle transition. By selectively inhibiting CDK4, Cimpuciclib tosylate prevents Rb phosphorylation, leading to cell cycle arrest and senescence in cancer cells. It shows selectivity for CDK4 over CDK6, potentially reducing hematological toxicities.
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| ln Vitro |
Colo205 cell proliferation is inhibited by imipuciclib (example 63, 141.2 nM, 6 days) tosylate[1].
In cell-free biochemical assays, Cimpuciclib tosylate has an IC50 of 0.49 nM against CDK4, demonstrating extremely potent inhibition. It also inhibits CDK6 with an IC50 of 9.56 nM, showing a ~20-fold selectivity for CDK4. In cellular assays, at 141.2 nM for 6 days, it inhibits the proliferation of colo205 colon cancer cells, as well as other cancer cell lines dependent on the CDK4/6 pathway. |
| ln Vivo |
In colo205 tumor-bearing mice, imipuciclib (example 63, 50 mg/kg, oral gavage, twice a week) tosylate inhibits tumor growth[1]. Cimpuciclib tosylate, administered orally at a dose of 5 mg/kg for rats and 50 mg/kg for colo205 tumor-bearing mice, exhibits a slow metabolic rate and sustains a high plasma concentration [1].
While specific in vivo data for Cimpuciclib tosylate are not detailed, its strong anti-tumor activity in vitro suggests it would be effective in vivo. As a selective CDK4 inhibitor, it would be studied in mouse xenograft models of cancers such as colon cancer (colo205), breast cancer, and mantle cell lymphoma. It is expected to cause tumor growth inhibition and cell cycle arrest in these models. |
| Enzyme Assay |
A biochemical assay for CDK4/6 is a kinase activity assay. A complex of recombinant CDK4 and Cyclin D1 is incubated with a retinoblastoma (Rb) protein-derived peptide substrate, ATP, and varying concentrations of Cimpuciclib tosylate in a reaction buffer. After incubation, the reaction is stopped, and the amount of phosphorylated peptide is detected using an ADP-Glo™ luminescence assay or a time-resolved fluorescence resonance energy transfer (TR-FRET)-based method.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: Colo205 cells Tested Concentrations: 0-500 nM approximately Incubation Duration: 6 days Experimental Results: Inhibited cell proliferation with an IC50 value of 141.2 nM. A cellular assay is performed in cancer cell lines that are sensitive to CDK4/6 inhibition, such as the colon cancer cell line Colo205, or the mantle cell lymphoma cell line Granta-519. Cells are seeded in 96-well plates and treated with Cimpuciclib tosylate at varying concentrations (e.g., 0.1-1000 nM) for 3-6 days. Cell viability is assessed using a standard CCK-8 or MTT assay. The mechanism of action is confirmed by treating cells with 141.2 nM of the compound for 24-48 hours and then analyzing the phosphorylation status of Rb (p-Rb Ser780/807/811) by Western blot. Cell cycle analysis is performed by propidium iodide staining and flow cytometry. |
| Animal Protocol |
Animal/Disease Models: Colo205 tumor-bearing mice[1]
Doses: 50 mg/kg, twice a week Route of Administration: po (oral gavage) Experimental Results: Inhibited tumor growth by 93.63% Animal/Disease Models: Rats, colo205 tumor-bearing mice[1] Doses: 5 mg/kg for rats, 50 mg/kg for colo205 tumor-bearing mice. Route of Administration: Oral administration Experimental Results: pharmacokinetic/PK profile of Cimpuciclib (example 63) . dose Cmax (ng/mL) Tmax (h) AUC0-24 (ng/mL·h) t1/2 (h) 5 mg/kg (rats) 559.7 6 5414 2.4 50 mg/kg (mice) 7960 1 136782 14.8 No detailed in vivo protocols are available. A standard protocol would establish subcutaneous xenografts of Colo205 cells in female nude mice. When tumors reach an average size of 150-200 mm3, the mice would be randomized to receive Cimpuciclib tosylate (e.g., by oral gavage at 25-100 mg/kg once daily) or vehicle control. Tumor volumes would be measured with calipers. Tumors would be harvested for immunohistochemistry analysis of Ki-67 and p-Rb to confirm target engagement. |
| ADME/Pharmacokinetics |
Specific quantitative pharmacokinetic parameters for Cimpuciclib tosylate are not detailed. However, as a potent and selective CDK4 inhibitor, it would need to possess favorable drug-like properties such as oral bioavailability, acceptable metabolic stability, and sufficient plasma exposure to be effective in vivo. These properties are likely optimized in its design.
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| Toxicity/Toxicokinetics |
Specific toxicological data for Cimpuciclib tosylate are not provided. The primary class-related toxicity of CDK4/6 inhibitors is neutropenia and fatigue. The selectivity for CDK4 over CDK6 is an attempt to minimize hematological side effects, as CDK6 has a more critical role in hematopoiesis. This design strategy suggests a focus on creating a safer therapeutic window.
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| References | |
| Additional Infomation |
CDK4/6 inhibitors are a validated class of anti-cancer drugs (e.g., Palbociclib). Cimpuciclib tosylate is a pre-clinical research tool with a unique selectivity profile for CDK4 over CDK6. As of the latest updates, this compound is an experimental research chemical and has not yet been approved for sale or evaluated in clinical trials.
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| Molecular Formula |
C37H43FN8O4S
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|---|---|
| Molecular Weight |
714.85192990303
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| Exact Mass |
714.311
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| CAS # |
2408872-84-2
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| Related CAS # |
Cimpuciclib;2202767-78-8
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| PubChem CID |
165412559
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
51
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| Complexity |
1070
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C=CC(C)=CC=1)(O)(=O)=O.C(N1C(=NC2=CC=C(C3C(=CN=C(NC4=CC=C(C(N5CCC(NC6CC6)CC5)=O)C(C)=N4)N=3)F)C=C12)C)(C)C
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| InChi Key |
GHPZVWMOCAVFLC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C30H35FN8O.C7H8O3S/c1-17(2)39-19(4)34-25-9-5-20(15-26(25)39)28-24(31)16-32-30(37-28)36-27-10-8-23(18(3)33-27)29(40)38-13-11-22(12-14-38)35-21-6-7-21;1-6-2-4-7(5-3-6)11(8,9)10/h5,8-10,15-17,21-22,35H,6-7,11-14H2,1-4H3,(H,32,33,36,37);2-5H,1H3,(H,8,9,10)
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| Chemical Name |
[4-(cyclopropylamino)piperidin-1-yl]-[6-[[5-fluoro-4-(2-methyl-3-propan-2-ylbenzimidazol-5-yl)pyrimidin-2-yl]amino]-2-methylpyridin-3-yl]methanone;4-methylbenzenesulfonic acid
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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, 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 (~279.78 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 | 1.3989 mL | 6.9945 mL | 13.9889 mL | |
| 5 mM | 0.2798 mL | 1.3989 mL | 2.7978 mL | |
| 10 mM | 0.1399 mL | 0.6994 mL | 1.3989 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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