2. Cell Cycle/DNA Damage Stem Cell/Wnt PI3K/Akt/mTOR MAPK/ERK Pathway Protein Tyrosine Kinase/RTK JAK/STAT Signaling Epigenetics
  3. CDK GSK-3 MEK JAK
  4. RGB-286638

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.

RGB-286638 Chemical Structure

RGB-286638 Chemical Structure

CAS No. : 784210-87-3

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10 mM * 1 mL in DMSO
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Solid
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Customer Review

Based on 2 publication(s) in Google Scholar

Other Forms of RGB-286638:

RGB-286638 Related Antibodies

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GSK-3 GSK-3α GSK-3β

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MEK1 MEK2 MEK5 MEK

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JAK1 JAK2 JAK3 Tyk2 JAK

  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

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.

IC50 & Target[1]

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)

In Vitro

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.

RGB-286638 Related Antibodies
In Vivo

Dose-finding studies with RGB-286638 identify 40 mg/kg/day IV treatment as the maximum tolerated dose in SCID mice. Five days IV treatment with RGB-286638 significantly suppresses MM tumor growth, with maximum TGI (%) noted at day 14 following end of treatment at 85.06% and 86.34% in the 30 mg/kg and 40 mg/kg treated cohorts respectively. The log10 cell kill (LCK Td: 4.5 days) is 1.6 for both treated groups. RGB-286638 treatment is also associated with improved survival, evidenced by first death at day 24 in controls versus day 43 in both treated groups. No toxic deaths occurred during this study: maximum percentage of body weight (BW) loss is observed on day 5 (8.4%) at 30 mg/kg dosage schedule, and on day 15 (9.9%) after 40 mg/kg dosing, with weight recovery in the following two weeks[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
Molecular Weight

618.55

Formula

C29H37Cl2N7O4
CAS No.
Appearance

Solid

Color

Light yellow to yellow

SMILES

O=C(NN1CCOCC1)NC2=CC=CC(C3=C4C(C5=CC=C(CN6CCN(CCOC)CC6)C=C5)=NN3)=C2C4=O.[H]Cl.[H]Cl
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Solvent & Solubility
In Vitro: 

DMSO : ≥ 150 mg/mL (242.50 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

H2O : 25 mg/mL (40.42 mM; Need ultrasonic)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.6167 mL 8.0834 mL 16.1668 mL
5 mM 0.3233 mL 1.6167 mL 3.2334 mL
View the 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 (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

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.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 7.5 mg/mL (12.13 mM); Clear solution

    This protocol yields a clear solution of ≥ 7.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (75.0 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.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 7.5 mg/mL (12.13 mM); Clear solution

    This protocol yields a clear solution of ≥ 7.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (75.0 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.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Calculation results:
Working solution concentration: mg/mL
This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only.If necessary, please contact MedChemExpress (MCE).
Purity & Documentation

Purity: 99.70%

SDS (251 KB)

COA (250 KB) LCMS (90 KB)

Handling Instructions (2659 KB)
References
Kinase Assay
[1]

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay
[1]

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[1]

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.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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 (sealed storage, away from moisture). 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
H2O / DMSO 1 mM 1.6167 mL 8.0834 mL 16.1668 mL 40.4171 mL
5 mM 0.3233 mL 1.6167 mL 3.2334 mL 8.0834 mL
10 mM 0.1617 mL 0.8083 mL 1.6167 mL 4.0417 mL
15 mM 0.1078 mL 0.5389 mL 1.0778 mL 2.6945 mL
20 mM 0.0808 mL 0.4042 mL 0.8083 mL 2.0209 mL
25 mM 0.0647 mL 0.3233 mL 0.6467 mL 1.6167 mL
30 mM 0.0539 mL 0.2694 mL 0.5389 mL 1.3472 mL
40 mM 0.0404 mL 0.2021 mL 0.4042 mL 1.0104 mL
DMSO 50 mM 0.0323 mL 0.1617 mL 0.3233 mL 0.8083 mL
60 mM 0.0269 mL 0.1347 mL 0.2694 mL 0.6736 mL
80 mM 0.0202 mL 0.1010 mL 0.2021 mL 0.5052 mL
100 mM 0.0162 mL 0.0808 mL 0.1617 mL 0.4042 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

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RGB-286638 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

RGB-286638784210-87-3RGB286638RGB 286638CDKGSK-3MEKJAKCyclin dependent kinaseGlycogen synthase kinase-3Glycogen synthase kinase 3Mitogen-activated protein kinase kinaseMAPKKMAP2KJanus kinaseInhibitorinhibitorinhibit

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