GSK2801 |
| Catalog No.GC15789 |
GSK2801 est un inhibiteur des bromodomaines BAZ2A et BAZ2B puissant, sélectif, actif par voie orale et actif sur les cellules, avec des valeurs de Kd de 136 nM et 257 nM, respectivement. GSK2801 montre une sélectivité >50 fois pour BAZ2A/B par rapport À BRD4.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1619994-68-1
Sample solution is provided at 25 µL, 10mM.
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GSK2801, as an inhibitor of BAZ2A and BAZ2B bromodomains, is potent, selective and cell active acetyl-lysine competitive, with dissociation constants (KD) of 136 and 257 nM for binding to BAZ2B and BAZ2A, respectively [1].
Bromodomains, as protein interaction domains, are acetyl-lysine specific. Bromodomain containing proteins BAZ2A and BAZ2B are closely related. The nucleolar remodeling complex (NoRC) regulates the expression of noncoding RNAs. BAZ2A and BAZ2B constitute the central scaffolding protein of NoRC [1].
In U2OS cells, treatment with the SAHA induced hyperacetylated chromatin. In a GFP-BAZ2A fusion construct, the conserved asparagines that are essential for recognizing the acetylated lysine has been mutated. When a GFP-BAZ2A fusion construct was transfected into SAHA-treated U2OS cells, the mutant construct accelerated FRAP half-recovery time. Treatment with GSK2801 alone in U2OS cells also accelerated FRAP half-recovery time. Both acceleration extents are the same. This meant that GSK2801 can displace BAZ2A from chromatin [1].
Pharmacokinetic parameters of GSK2801 after intraperitoneal and oral dosing to male CD1 mice were measured. Data showed that after oral dosing in vivo, GSK2801 has reasonable exposure, reasonable plasma stability and modest clearance. GSK2801 can be used as an inhibitor of BAZ2A/B bromodomain in vivo [1]. No more in vivo data of the treatment with GSK2801 are found.
Reference:
[1]. Chen P, Chaikuad A, Bamborough P, et al. Discovery and Characterization of GSK2801, a Selective Chemical Probe for the Bromodomains BAZ2A and BAZ2B. Journal of medicinal chemistry, 2015.
| Cell experiment [1]: | |
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Cell lines |
U2OS cells |
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Preparation method |
The solubility of this compound in DMSO is > 18.6 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
|
Reacting condition |
1 μM; 1 hr |
|
Applications |
In the U2OS cells transfected with a GFP-BAZ2A fusion construct, GSK2801 reduced FRAP half-recovery time to the same extent as observed for the U2OS cells transfected with a mutant construct after SAHA treatment, which indicated that GSK2801 displaced BAZ2A from chromatin. |
| Animal experiment [1]: | |
|
Animal models |
Male CD1 mice |
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Dosage form |
30 mg/kg; i.p. or p.o. |
|
Applications |
In a male CD1 mouse, a single dose of GSK2801 (30 mg/kg; p.o.) resulted in reasonable in vivo exposure and plasma stability, as well as modest clearance (Tmax = 1.0 hr; Cmax = 435 ng/mL; T1/2 = 1.5 hrs), which implied that GSK2801 could be used as BAZ2A/B bromodomain inhibitor in vivo. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Chen P, Chaikuad A, Bamborough P, Bantscheff M, Bountra C, Chung CW, Fedorov O, Grandi P, Jung D, Lesniak R, Lindon M, Müller S, Philpott M, Prinjha R, Rogers C, Selenski C, Tallant C, Werner T, Willson TM, Knapp S, Drewry DH. Discovery and Characterization of GSK2801, a Selective Chemical Probe for the Bromodomains BAZ2A and BAZ2B. J Med Chem. 2016 Feb 25;59(4):1410-24. | |
| Cas No. | 1619994-68-1 | SDF | |
| Chemical Name | 1-(1-(2-(methylsulfonyl)phenyl)-7-propoxyindolizin-3-yl)ethanone | ||
| Canonical SMILES | CCCOC(C=CN12)=CC2=C(C3=CC=CC=C3S(C)(=O)=O)C=C1C(C)=O | ||
| Formula | C20H21NO4S | M.Wt | 371.45 |
| Solubility | ≥ 18.55mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6922 mL | 13.4608 mL | 26.9215 mL |
| 5 mM | 0.5384 mL | 2.6922 mL | 5.3843 mL |
| 10 mM | 0.2692 mL | 1.3461 mL | 2.6922 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 15 reference(s) in Google Scholar.)
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