Suberoyl bis-hydroxamic acid (Suberohydroxamic acid; SBHA) is a competitive, cell-permeable (penetrable) inhibitor of HDAC1 and HDAC3 with ID50 values of 0.25 μM and 0.30 μM, respectively. Suberoyl bis-hydroxamic acid makes tumor cells susceptible to apoptosis and promotes the mitochondrial apoptotic pathway. Suberoyl bis-hydroxamic acid may be utilized in the study of medullary thyroid carcinoma (MTC).

Physicochemical Properties

Molecular Formula	C8H16N2O4
Molecular Weight	204.22
Exact Mass	204.111
CAS #	38937-66-5
PubChem CID	5173
Appearance	White to off-white solid powder
Density	1.2±0.1 g/cm3
Melting Point	153-155ºC(lit.)
Index of Refraction	1.502
LogP	-1.81
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	7
Heavy Atom Count	14
Complexity	164
Defined Atom Stereocenter Count	0
InChi Key	IDQPVOFTURLJPT-UHFFFAOYSA-N
InChi Code	InChI=1S/C8H16N2O4/c11-7(9-13)5-3-1-2-4-6-8(12)10-14/h13-14H,1-6H2,(H,9,11)(H,10,12)
Chemical Name	N,N'-dihydroxyoctanediamide
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	HDAC1 0.25 μM (IC50) HDAC3 0.30 μM (IC50)
ln Vitro	The degree of apoptosis is improved when Suberoyl bis-hydroxamic acid (10, 20, or 50 μM; 24 hours) is combined with TRAIL. When TRAIL is paired with 20 μM SBHA, which alone causes about 10-15% apoptosis, 45–50% of the cells die[1]. The expression of the proteins Bcl-xL and Mcl-1 is not significantly affected by suberoyl bis-hydroxamic acid (20–50 μM; 10–20 hours); Bax is slightly affected, though. It increases the ratio of relative protein expression of Bcl-xL and Bax when combined with TRAIL, whereas in MM-BI and Ist-Mes2 cells, the ratio of Mcl-1 and Bax changes later[1]. MEL cells accumulate acetylated histone H4 in response to 30 μM of suberoyl bis-hydroximac acid over a 6-hour duration[2].
ln Vivo	The administration of suberoyl bis-hydroxamic acid (200 mg/kg intraperitoneally every 2 days for 12 days) results in a significant rise in the active form of Notch1 (NICD) and a corresponding decrease in ASCL1. It slows the growth of MTC tumors[3].
Cell Assay	Apoptosis Analysis[1] Cell Types: MM-BI and Ist-Mes2 cells Tested Concentrations: 10 μM, 20 μM or 50 μM Incubation Duration: 24 hrs (hours) Experimental Results: demonstrated a cooperative effect in cell apoptosis.
Animal Protocol	Animal/Disease Models: Nude mice injected with human MTC cells[3] Doses: 200 mg/kg Route of Administration: intraperitoneal (ip)injection; every 2 days; 12 days Experimental Results: Resulted in an average 55% inhibition of tumor growth in SBHA treatment group.
References	[1]. Sensitization of Mesothelioma to TRAIL Apoptosis by Inhibition of Histone Deacetylase: Role of Bcl-xL Down-Regulation. Biochem Biophys Res Commun. 2004 Jan 30;314(1):186-91. [2]. A Class of Hybrid Polar Inducers of Transformed Cell Differentiation Inhibits Histone Deacetylases.Proc Natl Acad Sci U S A. [3]. Suberoyl Bishydroxamic Acid Activates notch1 Signaling and Suppresses Tumor Progression in an Animal Model of Medullary Thyroid Carcinoma. Ann Surg Oncol. 2008 Sep;15(9):2600-5.
Additional Infomation	N,N'-dihydroxyoctanediamide is a hydroxamic acid.

Solubility Data

Solubility (In Vitro)

DMSO : 50 mg/mL (244.83 mM) H2O : 8.33 mg/mL (40.79 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (12.24 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 (12.24 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 (12.24 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 4: 5 mg/mL (24.48 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.8967 mL	24.4834 mL	48.9668 mL
	5 mM	0.9793 mL	4.8967 mL	9.7934 mL
	10 mM	0.4897 mL	2.4483 mL	4.8967 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.