BI-7273 is a novel, potent, selective, and cell-permeable BRD9 inhibitor with IC50 and Kd of 19 and 0.75 nM, respectively; it also shows high effect on BRD7 with IC50 and Kd of 117 nM and 0.3 nM, respectively. BI-7273 may be useful in further exploring BRD9 bromodomain biology in both in vitro and in vivo settings. Selective inhibitors of bromodomain-containing protein 9 (BRD9) may have therapeutic potential in the treatment of human malignancies and inflammatory diseases.

Physicochemical Properties

Molecular Formula	C20H23N3O3
Molecular Weight	353.4149
Exact Mass	353.173
CAS #	1883429-21-7
Related CAS #	1883429-21-7; 2305379-66-0 (BRD7-IN-1 free base)
PubChem CID	118796358
Appearance	White to off-white solid powder
Density	1.2±0.1 g/cm3
Boiling Point	509.2±50.0 °C at 760 mmHg
Flash Point	261.8±30.1 °C
Vapour Pressure	0.0±1.3 mmHg at 25°C
Index of Refraction	1.590
LogP	1.85
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	5
Heavy Atom Count	26
Complexity	522
Defined Atom Stereocenter Count	0
InChi Key	RBUYFHLQNPJMQM-UHFFFAOYSA-N
InChi Code	InChI=1S/C20H23N3O3/c1-22(2)11-17-18(25-4)8-13(9-19(17)26-5)16-12-23(3)20(24)15-10-21-7-6-14(15)16/h6-10,12H,11H2,1-5H3
Chemical Name	4-(4-((dimethylamino)methyl)-3,5-dimethoxyphenyl)-2-methyl-2,7-naphthyridin-1(2H)-one
Synonyms	BI-7273; BI 7273; BI7273.
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

having an IC50 and Kd of 19 and 0.75 nM, respectively, BI-7273 is a cell-permeable, selective inhibitor of BRD9. It also exhibits strong effects on BRD7, having an IC50 and Kd of 117 nM and 0.3 nM, respectively. With Kds of 8.8 nM, 210 nM, 2600 nM, and 8600 nM, respectively, BI-7273 is also marginally active against a set of kinases that includes CECR2, BRPF1, BRD1, CREBBP, EP300, FALZ, TAF1(2), and TAF1L(2). 1000 nM, 1200 nM, 850 nM, and 10,000 nM. The U2OS cell line exhibits activity with 1 μM of BI-7273. With an EC50 of 1400 nM, BI-7273 inhibits the growth of EOL-1 cells[1].

References

[1]. Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor. J Med Chem. 2016 May 26;59(10):4462-75. [2]. Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor. J Med Chem. 2016 May 26;59(10):4462-75.

Solubility Data

Solubility (In Vitro)

DMSO : ~10 mg/mL (~28.30 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1 mg/mL (2.83 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 10.0 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: 1 mg/mL (2.83 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 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: ≥ 1 mg/mL (2.83 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 10.0 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.