BI-9564 |
| Katalog-Nr.GC16817 |
BI-9564 ist ein potenter, selektiver und zellgÄngiger BRD9/BRD7-BromodomÄnen-Inhibitor mit IC50s von 75 nM und 3,4 μM und Kds von 14 nM bzw. 239 nM. BI-9564 hat einen IC50 von > 100 μM fÜr die BET-Familie.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1883429-22-8
Sample solution is provided at 25 µL, 10mM.
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IC50: 75 nM and 3.4 μM for BRD9 and BRD7 bromodomains, respectively
BI-9564 is a BRD9/7 specific inhibitor.
BRD7 and BRD9 are two important members of the bromodomain family protein. Both BRD7 and BRD9 have been implicated in chromatin remodeling.
In vitro: BI-9564 was identified as a BRD9/7 specific inhibitor via fragment-based screening and structure-guided design. BI-9564 was found to be bind to BRD9 with a higher affinity than to BRD7, and was negative on BET family proteins. In addition, BI-9564 demonstrated in vitro off-target selectivity to CECR2, but not in cells [1].
In vivo: In animal study, BomTac:NMRIFoxn1nu mice were given two oral doses daily and the concentration of BI-9564 in plasma was measured. Dose-dependent AUCs were obtained for BI-9564, achieving exposures that were higher compared to the EC50 level for EOL-1 cells. Moreover, when the oral treatment with BI-9564 at 180 mg/kg was initiated on day 5 and applied daily with an interruption at day 18 and 19, a significant reduction in tumour growth compared to controls was found on day 18 leading to a median tumour growth inhibition value of 52% [1].
Clinical trial: Up to now, BI-9564 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.
Cell experiment: | Cells are grown in 50 µL medium as specified by the supplier 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 before measuring viability via cellular ATP levels using the cell titer glow assay. |
Animal experiment: | Female CIEA-NOG mice are engrafted intravenously with 1×107 EOL-1 AML cells stably expressing luciferase and GFP. Following injection of the cells animals are randomized based on body weight (n=10/group). Treatment starts on day 5 with either 0.5% Natrosol or BI-9564 formulated with 0.5% Natrosol. All doses are calculated relative to the mouse body weight on the treatment day. BI-9564 and the vehicle control are administered orally with a dosing volume of 10 mL/kg body weight. BI-9564 is administered daily from day 5 until 17 and from day 20 until 22. Dosing is interrupted on day 18 for two days as one mouse in the treatment group reaches -15% body weight loss. Tumour load is measured 2-3 times weekly based on bioluminescence imaging. The following scoring system is used: score 0, no clinical signs; score 1, tail or hind limb weakness. Animals are sacrificed based on severity criteria including appearance of paralysis score 1 and/or body weight loss exceeding -18%. In S54 this tumor mouse model body weight changes can occur due to increased tumor load or due to intolerability. |
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. | 1883429-22-8 | SDF | |
| Chemical Name | 4-(4-((dimethylamino)methyl)-2,5-dimethoxyphenyl)-2-methyl-2,7-naphthyridin-1(2H)-one | ||
| Canonical SMILES | O=C1N(C)C=C(C2=CC(OC)=C(CN(C)C)C=C2OC)C3=CC=NC=C13 | ||
| Formula | C20H23N3O3 | M.Wt | 353.41 |
| Löslichkeit | DMF: 5 mg/ml,DMF:PBS(pH 7.2)(1:1): 0.5 mg/ml,DMSO: 5 mg/ml,Ethanol: 2 mg/ml | 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
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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
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 22 reference(s) in Google Scholar.)
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