BRD73954 (BRD-73954) is a novel, potent and dual inhibitor of histone deacetylase 6 (HDAC6) and HDAC8 with potential anticancer activity. Its IC50 values for HDAC6 and HDAC8 inhibition are 36 and 120 nM, respectively.

Physicochemical Properties

Molecular Formula	C16H16N2O3
Molecular Weight	284.31
Exact Mass	284.116
Elemental Analysis	C, 67.59; H, 5.67; N, 9.85; O, 16.88
CAS #	1440209-96-0
Related CAS #	1440209-96-0
PubChem CID	71680913
Appearance	White to off-white solid powder
Density	1.2±0.1 g/cm3
Index of Refraction	1.613
LogP	1.19
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	5
Heavy Atom Count	21
Complexity	353
Defined Atom Stereocenter Count	0
SMILES	O=C(C1C([H])=C([H])C([H])=C(C(N([H])O[H])=O)C=1[H])N([H])C([H])([H])C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H]
InChi Key	FIHKWEQJEDRIFS-UHFFFAOYSA-N
InChi Code	InChI=1S/C16H16N2O3/c19-15(17-10-9-12-5-2-1-3-6-12)13-7-4-8-14(11-13)16(20)18-21/h1-8,11,21H,9-10H2,(H,17,19)(H,18,20)
Chemical Name	3-N-hydroxy-1-N-(2-phenylethyl)benzene-1,3-dicarboxamide
Synonyms	BRD-73954; BRD73954; BRD 73954
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	HDAC6 ( IC50 = 0.036 μM ); HDAC8 ( IC50 = 0.12 μM ); HDAC2 ( IC50 = 9 μM )
ln Vitro	BRD73954 is superior to the other class I and II histone deacetylases (HDACs) in terms of selectivity toward HDAC6 and HDAC8, with IC50 values of 36 nM and 120 nM, respectively, as well as HDAC5, >33 μM, HDAC7, 13 μM, HDAC8, 120 nM, and HDAC9, >33 μM. Treatment with BRD73954 causes α-tubulin acetylation to rise significantly. [1]
ln Vivo	N/A
Enzyme Assay	RD73954 ia a novel inhibitor of HDAC with IC50 of 36 nM and 120 nM for HDAC6 and HDAC8, respectively.
Cell Assay	The first small molecule inhibitor of histone deacetylase (HDAC), BRD73954 can potently and selectively inhibit both HDAC6 and HDAC8, even though these isoforms are related to different phylogenetic classes of the HDAC family of enzymes. Our findings reveal that phenyl hydroxamic acid meta substituents are easily incorporated into HDAC6 binding sites and are also required for the strong inhibition of HDAC8. When HeLa cells are treated with BRD73954, there is a noticeable rise in the acetylation of α-tubulin, which is a known substrate for HDAC6, but not of histone H3, which is a substrate for HDAC1, 2, and 3.
Animal Protocol	NA NA
References	[1]. Discovery of the first histone deacetylase 6/8 dual inhibitors. J Med Chem. 2013 Jun 13;56(11):4816-20.

Solubility Data

Solubility (In Vitro)

DMSO: 25~56 mg/mL (87.9~197.0 mM) Water: <1 mg/mL Ethanol: ~2 mg/mL warmed (~9.3 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.79 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 (8.79 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (8.79 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.5173 mL	17.5864 mL	35.1729 mL
	5 mM	0.7035 mL	3.5173 mL	7.0346 mL
	10 mM	0.3517 mL	1.7586 mL	3.5173 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.