N,N'-Dihydroxyoctanediamide

Names

[ Name ]:
N,N'-Dihydroxyoctanediamide

[Synonym ]:
Octanediamide, N,N-dihydroxy-
octane-1,8-dihydroxamic acid
N,N'-Dihydroxyoctanediamide
MFCD00192455

Biological Activity

[Description]:

Suberoyl bis-hydroxamic acid (Suberohydroxamic acid; SBHA) is a competitive and cell-permeable HDAC1 and HDAC3 inhibitor with ID50 values of 0.25 μM and 0.30 μM, respectively[1].Suberoyl bis-hydroxamic acid renders MM cells susceptible to apoptosis and facilitates the mitochondrial apoptotic pathways[2].Suberoyl bis-hydroxamic acid can be used for the study of medullary thyroid carcinoma (MTC)[3].

[Related Catalog]:

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> HDAC

Signaling Pathways >> Epigenetics >> HDAC

[Target]

HDAC1:0.25 μM (IC50)

HDAC3:0.30 μM (IC50)

[In Vitro]

Suberoyl bis-hydroxamic acid (10, 20 or 50 μM; 24 hours) combination with TRAIL improves apoptosis extent, and when TRAIL is combined with 20 μM SBHA (itself causing only 10–15% apoptosis), resulting in 45–50% cell death[1]. Suberoyl bis-hydroxamic acid (20-50 μM; 10-20 hours) alone has little effect on the expression of the proteins Bcl-xL, Mcl-1, and has albeit mildeffect on Bax. When it combines with TRAIL,which increases the ratio of relative protein expression of Bcl-xL and Bax in early periods, while the change in the ratio of Mcl-1 and Bax increases later in MM-BI and Ist-Mes2 cells[1]. Suberoyl bis-hydroxamic acid (30 μM; 6 hours) causes accumulation of acetylated histone H4 in MEL cells[2]. Apoptosis Analysis[1] Cell Line: MM-BI and Ist-Mes2 cells Concentration: 10 μM, 20 μM or 50 μM Incubation Time: 24 hours Result: Showed a cooperative effect in cell apoptosis.

[In Vivo]

Suberoyl bis-hydroxamic acid (intraperitoneal injection; 200 mg/kg; every 2 days; 12 days) reveals a marked increase in the active form of Notch1 (NICD) with a concomitant decrease in ASCL1. It reduces the MTC tumor growth[3]. Animal Model: Nude mice injected with human MTC cells[3] Dosage: 200 mg/kg Administration: Intraperitoneal injection; every 2 days; 12 days Result: Resulted in an average 55% inhibition of tumor growth in SBHA treatment group.

[References]

[1]. Jiri Neuzil, et al. 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]. V M Richon, et al. A Class of Hybrid Polar Inducers of Transformed Cell Differentiation Inhibits Histone Deacetylases.Proc Natl Acad Sci U S A

[3]. Li Ning, et al. 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.

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Melting Point ]:
153-155ºC(lit.)

[ Molecular Formula ]:
C₈H₁₆N₂O₄

[ Molecular Weight ]:
204.224

[ Exact Mass ]:
204.111008

[ PSA ]:
98.66000

[ LogP ]:
-1.81

[ Appearance of Characters ]:
lyophilized powder

[ Index of Refraction ]:
1.502

[ Storage condition ]:
−20°C

[ Water Solubility ]:
H2O: soluble

MSDS

Click to get detail MSDS

Safety Information

[ Safety Phrases ]:
22-24/25

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ HS Code ]:
2924199090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2924199090

[ Summary ]:
2924199090. other acyclic amides (including acyclic carbamates) and their derivatives; salts thereof. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%

Articles

A regimen combining the Wee1 inhibitor AZD1775 with HDAC inhibitors targets human acute myeloid leukemia cells harboring various genetic mutations.

Leukemia 29(4) , 807-18, (2015)

AZD1775 targets the cell cycle checkpoint kinase Wee1 and potentiates genotoxic agent cytotoxicity through p53-dependent or -independent mechanisms. Here, we report that AZD1775 interacted synergistic...

Reactive oxygen species, glutathione, and thioredoxin influence suberoyl bishydroxamic acid-induced apoptosis in A549 lung cancer cells.

Tumour Biol. 36 , 3429-39, (2015)

Suberoyl bishydroxamic acid (SBHA) as a histone deacetylase (HDAC) inhibitor can induce apoptosis through the formation of reactive oxygen species (ROS). However, there is no report about the regulati...

Down-Regulation of Thioredoxin1 Is Involved in Death of Calu-6 Lung Cancer Cells Treated With Suberoyl Bishydroxamic Acid.

J. Cell. Biochem. 117 , 1250-61, (2016)

Suberoyl bishydroxamic acid (SBHA), a histone deacetylase (HDAC) inhibitor, can show an anticancer effect. In this study, we investigated the effects of SBHA on the growth inhibition and death of Calu...