CDK4/6-IN-15
Based on 1 Customer Validation
CDK4/6-IN-15 is an orally active and selective CDK4/6 inhibitor. CDK4/6-IN-15 potently inhibits cancer cells growth. CDK4/6-IN-15 arrests cell cycle at G1 phase and suppresses retinoblastoma tumour suppressor protein (Rb) phosphorylation at S780 and E2 factor (E2F)-regulated gene expression.
For research use only. We do not sell to patients.
- Purity : 99.32%
- CAS No.: 2078047-99-9
- Formula: C21H27FN8S
- Molecular Weight:442.56
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Storage:
4°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]|
CDK4 3 nM (IC50) |
CDK6 0.279 μM (IC50) |
CDK2 3.335 μM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| MDA-MB-453 | GI50 |
0.325 μM
Compound: 40a
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Antiproliferative activity against human MDA-MB-453 cells assessed as cell growth inhibition incubated for 72 hrs by MTT assay
Antiproliferative activity against human MDA-MB-453 cells assessed as cell growth inhibition incubated for 72 hrs by MTT assay
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[PMID: 32707525] |
| MV4-11 | GI50 |
0.107 μM
Compound: 40a
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Antiproliferative activity against human MV4-11 cells assessed as cell growth inhibition incubated for 72 hrs by resazurin assay
Antiproliferative activity against human MV4-11 cells assessed as cell growth inhibition incubated for 72 hrs by resazurin assay
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[PMID: 32707525] |
In Vitro
CDK4/6-IN-15 (compound 91) (10 μM; 24 h) also potently inhibits FLT3 and MYLK4 with inhibition rates >90%[1].
CDK4/6-IN-15 (0-5 μM; 72 h) suppresses tumour cell proliferation selectively with GI50s of 0.107 μM (MV4-11) and 0.325 μM (MDA-MB-453)[1].
CDK4/6-IN-15 (0.1-1 μM; 24 h) arrests exclusively the cell cycle at G1 phase in Rb-positive MV4-11 cells and MDA-MB-453 cells[1].
CDK4/6-IN-15 (0.1-1 μM or 0.3-3 μM; 24-96 h) triggers apoptosis in MV4-11 and MDA-MB-453 cells[1].
CDK4/6-IN-15 (0.1-3.3 μM; 4-24 h) inhibits phosphorylation of Rb[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:MV4-11 and MDA-MB-453 cells
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Concentration:0.1 μM, 0.5 μM, and 1 μM for MV4-11; 0.3 μM, 0.6 μM, and 3.3 μM for MDA-MB-453 cells
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Incubation Time:24 h, 48 h, 72 h, and 96 h
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Result:Induced cell apoptosis via arresting cell cycle at G1 accompanied with Rb) phosphorylation suppression and E2F-regulated gene expression decreases.
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Cell Line:MV4-11 (GI50=0.107 μM) and MDA-MB-453 (GI50=0.325 μM)
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Concentration:1×, 5×, 10× GI50
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Incubation Time:4 h, 12 h, and 24 h
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Result:Resulted inhibition of Rb phosphorylation at S780.
In Vivo
Pharmacokinetic Analysis[1]
| Route | Dose (mg/kg) | CL (mL/min/kg) | Vss (L/kg) | AUC (μM·h) | Cmax (μM) | Tmax (h) | t1/2 (h) | F (%) | |
| rat | IV | 5 | 155 | 27.5 | 1.2 | 1.4 | / | 2.1 | / |
| PO | 20 | / | / | 4.4 | 0.3 | 4.3 | 20.3 | 95 | |
| mouse | IV | 2 | 90 | 15.7 | 0.7 | 1.3 | / | 2.9 | / |
| PO | 10 | / | / | 4.3 | 0.6 | 2.5 | 2.7 | 129 |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 2078047-99-9
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Appearance Solid
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Molecular Weight 442.56
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Formula C21H27FN8S
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Color Light yellow to yellow
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SMILES
CNC1=NC(C)=C(C2=NC(NC3=NC=C(N4CCC(N(C)C)CC4)C=C3)=NC=C2F)S1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
Solvent & Solubility
In Vitro:
DMSO : 5 mg/mL (11.30 mM; ultrasonic and warming and heat to 60°C; 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.
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.
Protocols
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Kinase activity and phosphorylation assays
Kinase activity assays measure the ability of kinases to transfer phosphate groups from ATP to specific substrates, while phosphorylation assays detect the presence and levels of phosphorylated proteins. Common methods include radiolabeled ATP incorporation (e. g. ,), ADP release detection via bioluminescence (e. g. ,[3]), enzyme-linked immunosorbent assays (ELISA) for phospho-specific epitopes (e. g. ,[6]), and microtiter-based formats for high-throughput screening (e. g. ,[8]). The ADP-Glo assay quantifies kinase activity by measuring ADP produced during phosphorylation using a luciferase-based system. Radiometric assays involve autoradiography or scintillation counting after incorporation of 32P-labeled ATP into substrate proteins. ELISA-based approaches rely on phospho-specific antibodies to detect activated kinases in cell lysates or purified samples.
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RT-PCR
Reverse transcription technology uses RNA as a template to synthesize DNA. RT-PCR is simple, specific and sensitive, and can be used to detect gene expression levels and expression differences in cells; detect RNA virus content; clone cDNA sequences of specific genes.
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Western Blot
Western blotting (WB) is a commonly used experimental method in molecular biology, biochemistry, and immunogenetics for identifying and quantifying target proteins. It combines gel electrophoresis with immunoassay, enabling researchers to analyze protein expression, post-translational modifications, and molecular weight.
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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Flow cytometric DNA-content cell-cycle staining
Flow cytometric DNA-content cell-cycle staining measures the fluorescence intensity of DNA-bound fluorochromes in single cells or nuclei to estimate DNA content distributions, allowing assignment of populations to G0/G1, S, and G2/M phases by DNA histogram deconvolution. Propidium iodide (PI) intercalates into DNA, and PI fluorescence is proportional to cellular DNA content when staining is performed under conditions that make DNA accessible and minimize non-DNA signal. Cells with G2/M DNA content are expected to show approximately twice the fluorescence intensity of G0/G1 cells, while S-phase cells occupy intermediate fluorescence values. PI-based DNA-content analysis can also detect cells with fractional DNA content, often reported as sub-G1, when DNA fragmentation and extraction during staining reduce retained DNA signal in apoptotic cells. DAPI is an alternative DNA fluorochrome for univariate DNA-content analysis, while bivariate approaches combining DNA content with proliferation
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BrdU Incorporation Assay
Bromodeoxyuridine (BrdU) incorporation assay is based on the principle that BrdU, a thymidine analog, is incorporated into newly synthesized DNA during the S phase of the cell cycle, thereby serving as a marker of DNA replication and cellular proliferation. Incorporated BrdU can be detected using anti-BrdU antibodies following DNA denaturation, enabling visualization or quantification of proliferating cells through immunochemical detection methods such as immunofluorescence or immunohistochemistry.
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Protocol for Cell Cycle
Cell-cycle analysis by flow cytometry measures DNA content in single cells to estimate the fraction of cells in G0/G1, S, and G2/M phases. Propidium iodide intercalates into DNA, and after RNA removal with RNase, fluorescence intensity reflects cellular DNA content: 2N cells are assigned to G0/G1, cells between 2N and 4N to S phase, and 4N cells to G2/M. DNA-content analysis alone cannot reliably separate G0 from G1 or G2 from M. Ki-67 can distinguish quiescent G0 cells from cycling cells, EdU or BrdU incorporation marks active DNA synthesis in S phase, and phospho-histone H3 staining identifies mitotic cells within the 4N population.
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Protocol for Kinase activity and phosphorylation assays
Kinase activity assays measure transfer of phosphate from ATP to a protein or peptide substrate, generating phosphorylated substrate, ADP, or incorporated radiolabeled phosphate as the readout; phosphorylation assays measure site-specific phosphorylation in cells or tissues as a proxy for kinase-pathway activation, inhibition, or substrate regulation. Phosphorylation can be detected by phospho-specific Western blot, immunoprecipitation kinase assay, phospho-immunofluorescence, phospho-flow cytometry, luminescent ADP detection, radiolabeled ATP incorporation, or reporter-based pathway assays, and these readouts can be applied to cancer cells, primary neurons, mouse tumors, organoids, inflammatory macrophages, ferroptosis studies, and mitophagy studies when the kinase target is biologically relevant.
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Real Time qPCR (Q-PCR)
Real-time quantitative PCR (qPCR) quantifies an amplifiable nucleic-acid target by monitoring fluorescence during PCR cycling rather than measuring product only after amplification. The increase in fluorescence tracks accumulation of PCR product, and the quantification cycle (Cq; historically also Ct/CP) is related to the initial amount of target: samples containing more starting target generally reach the defined fluorescence threshold in fewer cycles.
Purity & Documentation
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Data Sheet (274 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 | 2.2596 mL | 11.2979 mL | 22.5958 mL | 56.4895 mL |
| 5 mM | 0.4519 mL | 2.2596 mL | 4.5192 mL | 11.2979 mL | |
| 10 mM | 0.2260 mL | 1.1298 mL | 2.2596 mL | 5.6490 mL |
CDK4/6-IN-15 Related Classifications
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