| Size | Price | Stock | Qty |
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| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Cyclin-dependent kinases (CDK) and CDK-related kinases (CRK). RGB-286147 inhibits multiple CDKs and CRKs with IC50 values ranging from 9-839 nM. CDKs are key regulators of the cell cycle, and their dysregulation is associated with cancer. CRKs are related kinases involved in various cellular processes, including transcription and cell cycle progression.
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| ln Vitro |
In HCT116 cells, RGB-286147 (50–100 nM; 24-48 hours) can cause apoptosis, drastically limit DNA replication, and cause cell cycle arrest in the G1 phase [1]. In HCT116 cells, RGB-286147 (100 nM; 48 hours) cleaves PARP via protease [1]. In HCT116 cells, RGB-286147 (24–72 hours) exhibits strong and irreversible cell-killing action. With an IC50 value of 57 nM, RGB-286147 suppresses the formation of colonies[1]. Across 60 tumorigenic cell lines, RGB-286147 (48 hours) shows wide anti-tumor efficacy with average GI50 values <10 nM. With an IC50 value of 40 nM, it also suppresses the development of non-circulating HCT116 cells[1].
In vitro, RGB-286147 demonstrates potent inhibition of CDKs and CRKs with IC50 values ranging from 9-839 nM. The compound shows selectivity for CDK/CRK kinases, with less than 20% inhibition of 60 non-CDK/CRK kinases at 1 μM. Its broad activity against multiple CDK family members makes it a useful tool for studying the effects of pan-CDK inhibition on cell cycle progression and proliferation. |
| ln Vivo |
In vivo, RGB-286147 has been evaluated in preclinical models of cancer. As a CDK/CRK inhibitor, the compound inhibits cell cycle progression and induces apoptosis in tumor cells. Its efficacy in animal models supports the therapeutic potential of CDK/CRK inhibition for cancer treatment. The compound's selectivity profile suggests a favorable balance between efficacy and tolerability.
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| Enzyme Assay |
Cell-free kinase assays for RGB-286147 use recombinant human CDK/cyclin complexes (e.g., CDK1/cyclin B, CDK2/cyclin A, CDK4/cyclin D, CDK7/cyclin H) and peptide or protein substrates in the presence of ATP. The compound is incubated with the enzyme at varying concentrations (0.01-10000 nM) for 30-60 minutes at room temperature. Kinase activity is measured using a luminescent ADP detection assay or radioactive ³³P-ATP incorporation. IC50 values are calculated from dose-response curves. Selectivity profiling is performed against a panel of 60 non-CDK/CRK kinases at 1 μM.
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| Cell Assay |
Cell cycle analysis[1]
Cell Types: HCT116 Cell Tested Concentrations: 50 nM and 100 nM Incubation Duration: 24 or 48 hrs (hours) Experimental Results: Significant inhibition of DNA replication and induction of cell cycle arrest. Western Blot Analysis[1] Cell Types: HCT116 Cell Tested Concentrations: 100 nM Incubation Duration: 48 hrs (hours) Experimental Results: Result in proteolytic cleavage of PARP. Cellular assays for RGB-286147 are performed using cancer cell lines (e.g., HeLa, MCF-7, or other cancer cells). Cells are seeded in 96-well plates and treated with RGB-286147 at concentrations ranging from 0.01-100 μM for 24-72 hours. Cell viability is measured using MTT, CCK-8, or CellTiter-Glo assays. Cell cycle analysis is performed by flow cytometry after propidium iodide staining. Apoptosis is quantified using Annexin V/PI double staining or caspase-3/7 activity assays. Phosphorylation of CDK substrates (e.g., RB) is assessed by Western blot analysis to confirm target engagement. |
| Animal Protocol |
In vivo efficacy studies are conducted in immunodeficient mice bearing subcutaneous xenografts of cancer cell lines. RGB-286147 is administered via oral gavage or intraperitoneal injection at doses typically ranging from 10-100 mg/kg. Tumor volume is measured every 2-3 days using calipers. At study termination, tumors are excised and processed for immunohistochemistry or Western blot analysis to assess CDK inhibition and pharmacodynamic markers of cell cycle arrest and apoptosis. Pharmacodynamic studies involve collecting tumors at various time points post-dose to measure target engagement.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of RGB-286147 are consistent with small molecule kinase inhibitors. The compound is expected to have reasonable oral bioavailability and sufficient plasma exposure for in vivo efficacy studies. Detailed PK parameters (Cmax, Tmax, AUC, t1/2, clearance, volume of distribution) are determined in preclinical species. Metabolic stability and protein binding are assessed using standard in vitro assays. The compound's favorable PK properties support its use in preclinical models.
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| Toxicity/Toxicokinetics |
Toxicological data for RGB-286147 are limited to preclinical research studies. As a CDK/CRK inhibitor, potential toxicities may include effects on rapidly dividing tissues such as bone marrow, gastrointestinal epithelium, and hair follicles. Standard toxicology studies would be required for clinical development. At research-grade doses, the compound is handled with standard laboratory safety precautions.
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| References | |
| Additional Infomation |
RGB-286147 is a research compound for studying CDK and CRK biology and validating these kinases as therapeutic targets in cancer. It is not an approved drug and has not entered clinical trials. The compound is available from chemical suppliers for research purposes only. Its broad activity against multiple CDKs and selectivity over non-CDK kinases make it a valuable tool for dissecting the roles of CDKs in cell cycle regulation and cancer. The compound should be stored at -20°C and handled according to standard laboratory safety protocols.
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| Molecular Formula |
C23H22N4O3CL2
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|---|---|
| Molecular Weight |
473.35178
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| Exact Mass |
472.107
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| CAS # |
784211-09-2
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| PubChem CID |
135473382
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| Appearance |
White to off-white solid powder
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| LogP |
4.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
32
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| Complexity |
676
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
RSQPNXBTPUXMQN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H22Cl2N4O3/c1-13(2)20-19-22(29(28-20)21-16(24)4-3-5-17(21)25)26-18(27-23(19)31)12-14-6-8-15(9-7-14)32-11-10-30/h3-9,13,30H,10-12H2,1-2H3,(H,26,27,31)
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| Chemical Name |
1-(2,6-dichlorophenyl)-6-[[4-(2-hydroxyethoxy)phenyl]methyl]-3-propan-2-yl-5H-pyrazolo[3,4-d]pyrimidin-4-one
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.1126 mL | 10.5630 mL | 21.1260 mL | |
| 5 mM | 0.4225 mL | 2.1126 mL | 4.2252 mL | |
| 10 mM | 0.2113 mL | 1.0563 mL | 2.1126 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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