BRD4770 (BRD-4770) is a novel and selective inhibitor of G9a (a histone methyltransferase, also known as euchromatin histone methyltransferase 2 (EHMT2)) with anticancer activity. It inhibits G9a with an IC50 of 6.3 μM, and can induce cell senescence. It exhibits excellent antiproliferative activity against various cancer cell lines such as pancreatic cancer cells-PANC-1.

Physicochemical Properties

Molecular Formula	C25H23N3O3
Molecular Weight	413.47
Exact Mass	413.173
CAS #	1374601-40-7
Related CAS #	1374601-40-7
PubChem CID	72193870
Appearance	White to off-white solid powder
Density	1.2±0.1 g/cm3
Index of Refraction	1.625
LogP	5.49
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	8
Heavy Atom Count	31
Complexity	601
Defined Atom Stereocenter Count	0
InChi Key	UCGWYCMPZXDHNR-UHFFFAOYSA-N
InChi Code	InChI=1S/C25H23N3O3/c1-31-24(30)20-14-15-22-21(17-20)26-25(27-23(29)19-12-6-3-7-13-19)28(22)16-8-11-18-9-4-2-5-10-18/h2-7,9-10,12-15,17H,8,11,16H2,1H3,(H,26,27,29)
Chemical Name	methyl 2-benzamido-1-(3-phenylpropyl)benzimidazole-5-carboxylate
Synonyms	methyl 2-benzamido-1-(3-phenylpropyl)-1H-benzo[d]imidazole-5-carboxylate; BRD-4770; BRD 4770; BRD4770;
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	After 72 hours, PANC-1 cells treated with BRD4770 (0–20 µM) have fewer cells[1]. PANC-1 cells treated with BRD4770 (2.5–5 µM; 24 hours) have a 23% reduction in H3K9 trimethylation levels[1]. BRD4770 causes a pancreatic cancer cell line to exhibit a senescent phenotype. Moreover, BRD4770 causes G2/M cell-cycle arrest and suppresses both anchorage-dependent and -independent cell proliferation. While the ataxia telangiectasia and Rad3-related protein (ATR) pathway is unaffected, BRD4770 activates the ataxia telangiectasia mutated (ATM) route without causing DNA damage[1]. Without preventing histone deacetylases from functioning, BRD4770 also causes higher amounts of lysine acetylation in cells[1].
ln Vivo
Cell Assay	Cell Viability Assay [1] Cell Types: PANC-1 cells Tested Concentrations: 0 µM, 0.625 µM, 1.25 µM, 2.5 µM, 5 µM, 10 µM, 20 µM Incubation Duration: 72 hrs (hours) Experimental Results: decreased the number of cells after 72 h. Western Blot Analysis[1] Cell Types: PANC-1 cells Tested Concentrations: 2.5 µM, 5 µM Incubation Duration: 24 hrs (hours) Experimental Results: diminished H3K9 trimethylation level by 23% in PANC-1 cells.
Animal Protocol
References	[1]. A small-molecule probe of the histone methyltransferase G9a induces cellular senescence in pancreatic adenocarcinoma. ACS Chem Biol. 2012 Jul 20;7(7):1152-7.
Additional Infomation	2-benzamido-1-(3-phenylpropyl)-5-benzimidazolecarboxylic acid methyl ester is a member of benzimidazoles.

Solubility Data

Solubility (In Vitro)

DMSO: 27 mg/mL (65.3 mM) Water:<1 mg/mL Ethanol:<1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.05 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: 6.25 mg/mL (15.12 mM) in 0.5% Methylcellulose/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.4186 mL	12.0928 mL	24.1856 mL
	5 mM	0.4837 mL	2.4186 mL	4.8371 mL
	10 mM	0.2419 mL	1.2093 mL	2.4186 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.