BI-7273 |
| Catalog No.GC16726 |
BRD9 bromodomain inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1883429-21-7
Sample solution is provided at 25 µL, 10mM.
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IC50: 19 and 117 nM for BRD9 and BRD7, respectively.
BI-7273 is a BRD9 bromodomain inhibitor.
BRD9, a SWI/SNF subunit, is identified to have a key role in leukemia growth, and the BRD9 bromodomain (BD) has been shown to be critical for the proliferation of acute myeloid leukemia cells.
In vitro: BI-7273 was previously demonstrated to mimic genetic perturbation of BRD9. BI-7273 could also target BRD7 BD, a BD protein that was found in a subclass of SWI/SNF remodelling complexes sharing high sequence homology with BRD9. In addition, BI-7273 was able to form an additional positive interaction with the carbonyl of Asn100 in BRD9. Furthermore, BI-7273 showed no measurable activity against BET family BDs even up to a concentration of 100 μM in the biochemical Alpha assay [1].
In vivo: In order to explore the potential of BI-7273 as in-vivo chemical probe, female BomTac:NMRIFoxn1nu mice was orally administered two doses at 20 and 180 mg/ kg and the concentration of BI-7273 in plasma over time was measured. Results showed that dose-dependent but nonlinear AUC was observed for BI-7273, achieving exposure that was higher compared to the EC50 level determined for BI-7273 in proliferation assays with EOL-1 cells [1].
Clinical trial: Up to now, BI-7273 is still in the preclinical development stage.
Reference:
[1] Martin LJ et al. Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor. J Med Chem.2016 May 26;59(10):4462-75.
Kinase experiment: | His-tagged BRD9 is immobilized to a density of 2000-4000 RUs on flow cells 3 and 4 of a Biacore NTA-chip. Carbonic anhydrase II is immobilized at a similar density on flow cell 2 and a blank reference surface is generated on flow cell 1. The buffer is then switched to assay buffer (HBS-P+ = 10 mM HEPES, pH 7.4, 150 mM NaCl, 0.05 % P20 + 5 % DMSO) and the chip equilibrated for several hours before use for Kd determinations. To be able to correct for differences in bulk solvent refractive index caused by small variations in the DMSO concentration solvent correction samples are included at the beginning and end of the run. Compounds (BI-7273, etc.) are injected in concentration series (1:1 dilutions, 7 different concentrations), starting with a maximum concentration that is approximately 10-20-fold higher than the expected Kd. The concentration series are prepared in 96-well plates. In the case that the dilution window chosen for a particular compound does not appropriately bracket the Kd of the compound the measurement is repeated with an optimized starting concentration. Positive and negative control samples are included at regular intervals to be able to monitor the performance of the assay. CBS is used as a positive control for carbonic anhydrase II to check for integrity of the reference protein at regular intervals. To correct for the excluded volume effect a DMSO calibration series is prepared and the calibration samples are measured at the beginning and end of each run. Kd values are determined and averaged[1]. |
Cell experiment: | Cells are grown in 50 µL medium for 7 days starting with 500 and with 1000 cells per well of a 384 well plate in the presence of varying concentrations of compound (BI-7273, etc.) before measuring viability via cellular ATP levels using the cell titer glow assay[1]. |
References: [1]. Martin LJ, et al. Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor. J Med Chem. 2016 May 26;59(10):4462-75. | |
| Cas No. | 1883429-21-7 | SDF | |
| Chemical Name | 4-(4-((dimethylamino)methyl)-3,5-dimethoxyphenyl)-2-methyl-2,7-naphthyridin-1(2H)-one | ||
| Canonical SMILES | O=C1N(C)C=C(C2=CC(OC)=C(CN(C)C)C(OC)=C2)C3=CC=NC=C13 | ||
| Formula | C20H23N3O3 | M.Wt | 353.41 |
| Solubility | ≥ 35.3mg/mL in DMSO with gentle warming | 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 | 2.8296 mL | 14.1479 mL | 28.2957 mL |
| 5 mM | 0.5659 mL | 2.8296 mL | 5.6591 mL |
| 10 mM | 0.283 mL | 1.4148 mL | 2.8296 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
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 16 reference(s) in Google Scholar.)
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