BI-9564 is a novel, cell-permeable, noncytotoxic, potent, and selective inhibitor of BRD9 (bromodomain-containing protein) and BRD7 BD (bromodomains) with Kd values of 14.1 and 239 nM, and IC50 values of 75 nM and 3.4 µM for BRD9/7 respectively. Selective inhibitors of bromodomain-containing protein 9 (BRD9) may have therapeutic potential in the treatment of human malignancies and inflammatory diseases. BI-9564 is useful in further exploring BRD9 bromodomain biology in both in vitro and in vivo settings. BI-9564 (<5 10='' 324='' shows='' no='' activity='' against='' and='' at='' an='' inhibition=''>40% is observed for only 2 out of 55 GPCRs. BI-9564 has antiproliferative effect on human acute myeloid eosinophilic leukemia cell line EOL-1, with EC50 of 800 nM.

Physicochemical Properties

Molecular Formula	C20H23N3O3
Molecular Weight	353.41
Exact Mass	353.173
CAS #	1883429-22-8
Related CAS #	1883429-22-8
PubChem CID	117072549
Appearance	White to off-white solid powder
Density	1.2±0.1 g/cm3
Boiling Point	519.9±50.0 °C at 760 mmHg
Flash Point	268.3±30.1 °C
Vapour Pressure	0.0±1.4 mmHg at 25°C
Index of Refraction	1.590
LogP	2.05
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	5
Heavy Atom Count	26
Complexity	536
Defined Atom Stereocenter Count	0
InChi Key	BJFSUDWKXGMUKA-UHFFFAOYSA-N
InChi Code	InChI=1S/C20H23N3O3/c1-22(2)11-13-8-19(26-5)15(9-18(13)25-4)17-12-23(3)20(24)16-10-21-7-6-14(16)17/h6-10,12H,11H2,1-5H3
Chemical Name	4-[4-[(dimethylamino)methyl]-2,5-dimethoxyphenyl]-2-methyl-2,7-naphthyridin-1-one
Synonyms	BI-9564; BI 9564; BI9564
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	BI-9564 (<5 μM) exhibits no activity against 324 kinases, and only 2 out of 55 GPCRs exhibit an inhibition >40% at 10 μM. With an EC50 of 800 nM, BI-9564 exhibits antiproliferative activity on the human acute myeloid eosinophilic leukemia cell line EOL -1[1]. In comparison to the highly homologous bromodomain BRD7, which has been suggested to be a tumor suppressor and is down-regulated in cancer cells, BI-9564 exhibits a Kd of 73 nM for BRD7 and is >10-fold more selective for BRD9[2].
ln Vivo	Attractive ADME/PK profiles are demonstrated by BI-9564 (180 mg/kg, po) for in vivo proof-of-concept investigations. In a xenograft model of human AML, BI-9564 produces a small but significant additional survival benefit of 2 days compared to survival of the control group[1].
Animal Protocol	0.5% Natrosol. 10 mL/kg. Oral administration Female CIEA-NOG mice engrafted intravenously with 1×107 EOL-1 AML cells stably expressing luciferase and GFP.
References	[1]. Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor. J Med Chem. 2016 May 26;59(10):4462-75. [2]. An Advanced Tool To Interrogate BRD9. J. Med. Chem., 2016, 59 (10), pp 4459-4461.

Solubility Data

Solubility (In Vitro)

DMSO:16 mg/mL (45.27 mM) Water:<1 mg/mL Ethanol:3 mg/mL (8.48 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 0.83 mg/mL (2.35 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.83 mg/mL (2.35 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 0.83 mg/mL (2.35 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		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	0.2830 mL	1.4148 mL	2.8296 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.