RGB-286638 free base
Based on 3 publication(s) in Google Scholar
RGB-286638 is a CDK inhibitor that inhibits the kinase activity of cyclin T1-CDK9, cyclin B1-CDK1, cyclin E-CDK2, cyclin D1-CDK4, cyclin E-CDK3, and p35-CDK5 with IC50s of 1, 2, 3, 4, 5 and 5 nM, respectively; also inhibits GSK-3β, TAK1, Jak2 and MEK1, with IC50s of 3, 5, 50, and 54 nM.
For research use only. We do not sell to patients.
- Purity: 98.09%
- CAS No.: 784210-88-4
- Formula: C29H35N7O4
- Molecular Weight:545.63
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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
- Protocol
- Purity & Documentation
- References
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Help & FAQs
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Cell Cycle/DNA Damage Compound Library
HY-L004
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Epigenetics Compound Library
HY-L005
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Immunology/Inflammation Compound Library
HY-L007
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JAK/STAT Compound Library
HY-L008
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Kinase Inhibitor Library
HY-L009
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MAPK Compound Library
HY-L010
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PI3K/Akt/mTOR Compound Library
HY-L015
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Protein Tyrosine Kinase Compound Library
HY-L016
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Stem Cell Signaling Compound Library
HY-L017
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Wnt/Hedgehog/Notch Compound Library
HY-L020
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Anti-Cancer Compound Library
HY-L025
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Anti-Aging Compound Library
HY-L034
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Differentiation Inducing Compound Library
HY-L038
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Reprogramming Compound Library
HY-L039
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Oxygen Sensing Compound Library
HY-L045
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Ferroptosis Compound Library
HY-L051
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Glycolysis Compound Library
HY-L058
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Cytoskeleton Compound Library
HY-L060
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Anti-Alzheimer's Disease Compound Library
HY-L069
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Anti-Breast Cancer Compound Library
HY-L074
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Anti-Lung Cancer Compound Library
HY-L075
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Anti-Pancreatic Cancer Compound Library
HY-L077
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Anti-Blood Cancer Compound Library
HY-L079
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Anti-Cancer Metabolism Compound Library
HY-L083
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Neurodegenerative Disease-related Compound Library
HY-L086
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Anti-Obesity Compound Library
HY-L087
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Angiogenesis-Related Compound Library
HY-L088
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Glucose Metabolism Compound Library
HY-L092
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Anti-Liver Cancer Compound Library
HY-L101
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Anti-Colorectal Cancer Compound Library
HY-L103
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Antidepressant Compound Library
HY-L108
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Anti-Prostate Cancer Compound Library
HY-L124
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Anti-Pulmonary Fibrosis Compound Library
HY-L125
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Cancer Stem Cells Compound Library
HY-L135
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Pain-Related Compound Library
HY-L139
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Metabolic Enzyme Compound Library
HY-L146
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Autoimmune Disease Compound Library
HY-L156
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Highly Selective Inhibitors Library
HY-L158
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Serine/Threonine Kinase Inhibitor Library
HY-L164
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Anti-Hematopathy Compound Library
HY-L171
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Anti-Ovarian Cancer Compound Library
HY-L173
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Multi-Target Compound Library
HY-L176
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Bioactive Compound Library Max
HY-L181
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MCE Bioactive Compound Library
HY-L001V
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Bioactive Compound Library
HY-L001
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Anti-Brain Cancer Compound Library
HY-L188
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Protein Kinase Compound Library
HY-L196
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Cell Proliferation Compound Library
HY-L201
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High-Throughput Bioactive Compound Library
HY-L205
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Anti-Rheumatic Arthritis Compound Library
HY-L210
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Posttranslational Modification Library
HY-L226
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High-Efficiency Gene Editing Compound Library
HY-L244
Publications Citing Use of MedChemExpress (MCE) RGB-286638 free base
MoreAll MEK Isoforms
More
Biological Activity
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T1-CDK9 1 nM (IC50) |
cyclin B1-CDK1 2 nM (IC50) |
cyclin E-CDK2 3 nM (IC50) |
cyclin D1-CDK4 4 nM (IC50) |
cyclin E-CDK3 5 nM (IC50) |
p35-CDK5 5 nM (IC50) |
cyclin H-CDK7 44 nM (IC50) |
cyclin D3-CDK6 55 nM (IC50) |
GSK-3β 3 nM (IC50) |
JAK2 50 nM (IC50) |
MEK1 54 nM (IC50) |
Fms 1 nM (IC50) |
TAK1 5 nM (IC50) |
JNK1a1 17 nM (IC50) |
JNK1a2 40 nM (IC50) |
C-src 25 nM (IC50) |
AMPK 41 nM (IC50) |
RGB-286638 is an indenopyrazole-derived CDK inhibitor (CDKI) with Ki-nanomolar activity against transcriptional CDKs. RGB-286638 inhibits several tyrosine and serine/threonine non-CDK enzymes, i.e. GSK-3β, TAK1, AMPK, Jak2, MEK1. The dose- and time-dependent effect of treatment with RGB-286638 (12.5-100nM) is investigated on the growth of human p53-wt (MM.1S, MM.1R, and H929) and p53-mutant (U266, OPM1, and RPMI) MM cells by MTT assay, assessing viability at 24 and 48 hours. The half-maximally effective concentrations (EC50) range between 20 and 70 nM at 48 hours. Dose-dependent differences in growth among p53-wt and -mutant cells are observed after 50nM treatment, with p53-wt MM.1S, MM.1R and H929 being slightly more sensitive to RGB-286638 treatment at 48h[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 784210-88-4
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Appearance Solid
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Molecular Weight 545.63
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Formula C29H35N7O4
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Color Light yellow to green yellow
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SMILES
O=C(NN1CCOCC1)NC2=CC=CC(C3=C4C(C5=CC=C(CN6CCN(CCOC)CC6)C=C5)=NN3)=C2C4=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (3)
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Journal Impact Factor
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Most Recent
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Science
2017 Dec 1;358(6367):eaan4368. PMID: 29191878 -
Cancers (Basel)
Identification of New Vulnerabilities in Conjunctival Melanoma Using Image-Based High Content Drug Screening. [Abstract]2022 Mar 19;14(6):1575. PMID: 35326726 -
Solvent & Solubility
DMSO : 100 mg/mL (183.27 mM; Need ultrasonic and warming; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Ethanol : < 1 mg/mL (insoluble)
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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 5 mg/mL (9.16 mM); Clear solution
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 5 mg/mL (9.16 mM); Clear solution
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
For the following dissolution methods, please prepare the working solution directly:
It is recommended to prepare fresh solutions and use them promptly within a short period of time.
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.
Add each solvent one by one: 17% Solutol HS-15 in Saline
Solubility: 10 mg/mL (18.33 mM); Suspended solution; Need ultrasonic
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.
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.
Protocol
Nuclear proteins are isolated from MM.1S cells treated with 50nM RGB-286638 for 1, 4, and 8 h, using Nuclear Extraction Kit. Nuclear protein aliquots are added to the 96-well plate coated with specific double-stranded DNA sequence containing the p53 response element for overnight incubation. p53 in the nuclear extract is detected by addition of a specific primary antibody directed against p53. A secondary antibody conjugated to HRP is added to provide a sensitive colorimetric readout at 450 nm. All experiments are performed in triplicates[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Colorimetric assays are performed to assay drug activity at increasing concentrations of RGB-286638 (0-100nM). Expressing wild-type p53 (MM.1S, MM.1R, H929) or mutant-p53 (U266, OPM1, RPMI) cells from 24- or 48-h cultures are pulsed with 10μL of 5mg/mL MTT to each well, followed by incubation at 37°C for 4h, and addition of 100 μL isopropanol containing 0.04 HCl. Absorbance readings at a wavelength of 570nm (with correction using readings at 630nm) are taken on a spectrophotometer. All experiments are performed in triplicates[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Mice[1]
The in vivo anti-MM activity of RGB-286638 is evaluated in an MM xenograft model. RGB-286638 dosing solutions of 2 and 3 mg/mL in 5% dextrose/water (D5W) pH5.2, as well as D5W pH5.2 for vehicle control dosing group, are prepared and provided by Agennix AG. CB-17 severe combined immunodeficient (SCID) mice are used. Forty male 5-6 week old mice are irradiated (2 Gy [200 rad]) using cesium 137 (137Cs)-irradiator source); 24h after irradiation, 2.5×106 MM.1S cells are inoculated subcutaneously in the upper back. When tumor weight is approximately 100 mg, mice are randomly assigned into 3 cohorts receiving daily IV tail vein injections for 5 consecutive days with either RGB-286638 30 mg/kg (8 mice), 40 mg/kg (9 mice), or control vehicle alone (10 mice). Animals are monitored for body weight and tumor volume by caliper measurements every alternate day. Tumor volume is estimated. Survival is evaluated from the first day of treatment until death. Tumor growth is evaluated using caliper measurements from the first day of treatment until day of first sacrifice. Percentage tumor growth inhibition (TGI) is calculated.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (280 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.8327 mL | 9.1637 mL | 18.3274 mL | 45.8186 mL |
| 5 mM | 0.3665 mL | 1.8327 mL | 3.6655 mL | 9.1637 mL | |
| 10 mM | 0.1833 mL | 0.9164 mL | 1.8327 mL | 4.5819 mL | |
| 15 mM | 0.1222 mL | 0.6109 mL | 1.2218 mL | 3.0546 mL | |
| 20 mM | 0.0916 mL | 0.4582 mL | 0.9164 mL | 2.2909 mL | |
| 25 mM | 0.0733 mL | 0.3665 mL | 0.7331 mL | 1.8327 mL | |
| 30 mM | 0.0611 mL | 0.3055 mL | 0.6109 mL | 1.5273 mL | |
| 40 mM | 0.0458 mL | 0.2291 mL | 0.4582 mL | 1.1455 mL | |
| 50 mM | 0.0367 mL | 0.1833 mL | 0.3665 mL | 0.9164 mL | |
| 60 mM | 0.0305 mL | 0.1527 mL | 0.3055 mL | 0.7636 mL | |
| 80 mM | 0.0229 mL | 0.1145 mL | 0.2291 mL | 0.5727 mL | |
| 100 mM | 0.0183 mL | 0.0916 mL | 0.1833 mL | 0.4582 mL |
RGB-286638 free base Related Classifications
HY-15504A Related Classifications
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