BG45 (BG-45) is a novel, potent and selective class I HDAC inhibitor with potential anticancer activity. In cell-free experiments, it suppresses HDAC3, HDAC1, HDAC2, and HDAC6 with IC50s of 289 nM, 2.0 μM, 2.2 μM, and >20 μM, respectively. When it comes to inhibiting HDAC3, BG45 is more selective than HDAC1, 2 (IC50 = 289 nM). At IC50 >20 μM, it did not inhibit HDAC6. In a multiple myeloma mouse model, BG45 significantly reduced tumor growth when used alone or in combination with bortezomib. In MM, HDAC3 is a viable target for therapy, and the novel HDAC3 inhibitor BG45 is validated as a prototype.

Physicochemical Properties

Molecular Formula	C11H10N4O
Molecular Weight	214.22
Exact Mass	214.085
Elemental Analysis	C, 61.67; H, 4.71; N, 26.15; O, 7.47
CAS #	926259-99-6
Related CAS #	926259-99-6
PubChem CID	16773791
Appearance	Light yellow to yellow solid powder
Density	1.4±0.1 g/cm3
Boiling Point	319.0±32.0 °C at 760 mmHg
Flash Point	146.7±25.1 °C
Vapour Pressure	0.0±0.7 mmHg at 25°C
Index of Refraction	1.708
LogP	0.18
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	2
Heavy Atom Count	16
Complexity	246
Defined Atom Stereocenter Count	0
SMILES	O=C(C1C=NC=CN=1)NC1C(N)=CC=CC=1
InChi Key	LMWPVSNHKACEKW-UHFFFAOYSA-N
InChi Code	InChI=1S/C11H10N4O/c12-8-3-1-2-4-9(8)15-11(16)10-7-13-5-6-14-10/h1-7H,12H2,(H,15,16)
Chemical Name	N-(2-aminophenyl)pyrazine-2-carboxamide
Synonyms	BG 45; BG-45; BG45
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

Targets	HDAC3 ( IC50 = 0.289 μM ); HDAC1 ( IC50 = 2.0 μM ); HDAC2 ( IC50 = 2.2 μM ); HDAC6 ( IC50 > 20 μM )
ln Vitro	In vitro activity: BG45 (1.875-30 µM; 48 and 72 h) targets and inhibits the growth of multiple myeloma (MM) cells in a dose-dependent manner[1]. BG45 (15 µM; 0-48 h; MM.1S cells) causes apoptosis by cleaving caspase-3 and PARP[1]. BG45 (10 and 20 µM; 12 h; MM.1S cells) causes the histones H2A, H3, and H4 to become acetylated in a dose-dependent manner[1]. BG45 (10 and 20 µM; 10 h; MM.1S cells) causes the toxicity of multiple myeloma (MM) cells, which is linked to the downregulation of p-STAT3 and the hyperacetylation of histones and STAT3[1].
ln Vivo	BG45 (15–50 mg/kg; i.p.; five days a week for three weeks; CB17 SCID mice with MM.1S xenograft model) increases the in vivo cytotoxicity induced by bortezomib (HY-10227) and inhibits the growth of human multiple myeloma (MM) cells[1].
Cell Assay	The method of measuring 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide (MTT) dye absorbance is used to evaluate the growth inhibitory effects of BG45 in MM cell lines. [3H]thymidine uptake is used to measure the rate of DNA synthesis and, consequently, the proliferation of MM cells.
Animal Protocol	Dissolved in 10% dimethylacetamide in 10% Kolliphor HS15 in PBS; 50 mg/kg, 5 days a week; i.p. injection Mice bearing MM.1S xenograft
References	[1]. Histone deacetylase 3 as a novel therapeutic target in multiple myeloma. Leukemia. 2014 Mar;28(3):680-9. [2]. HDAC6 inhibitors modulate Lys49 acetylation and membrane localization of β-catenin in human iPSC-derived neuronal cells. ACS Chem Biol. 2015 Mar 20;10(3):883-90.
Additional Infomation	N-(2-aminophenyl)-2-pyrazinecarboxamide is an aromatic amide.

Solubility Data

Solubility (In Vitro)

DMSO: ~42 mg/mL (~196.1 mM) Water: <1 mg/mL Ethanol: ~2 mg/mL warmed (~9.3 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (11.67 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: ≥ 2.5 mg/mL (11.67 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 25.0 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.6681 mL	23.3405 mL	46.6810 mL
	5 mM	0.9336 mL	4.6681 mL	9.3362 mL
	10 mM	0.4668 mL	2.3340 mL	4.6681 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.