4-(4-chloro-2-methylphenoxy)-N-hydroxybutanamide

• ChemBase编号: 72672
• 分子式: C11H14ClNO3
• 平均质量: 243.68676
• 单一同位素质量: 243.06622099
• SMILES: c1c(cc(c(c1)OCCCC(=O)NO)C)Cl
• Canonical SMILES: ONC(=O)CCCOc1ccc(cc1C)Cl
• InChI: InChI=1S/C11H14ClNO3/c1-8-7-9(12)4-5-10(8)16-6-2-3-11(14)13-15/h4-5,7,15H,2-3,6H2,1H3,(H,13,14)
• InChIKey: JHSXDAWGLCZYSM-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 4-(4-chloro-2-methylphenoxy)-N-hydroxybutanamide
• IUPAC传统名: 4-(4-chloro-2-methylphenoxy)-N-hydroxybutanamide
• 别名: 4-(4-Chloro-2-methylphenoxy)-N-hydroxybutanamide; Droxinostat; Droxinostat

登记号

• CAS号: 99873-43-5
• MDL号: MFCD01326592
• PubChem SID: 162037593
• PubChem CID: 568416

理论计算性质

• Acid pKa: 8.906647
• 质子受体: 3
• 质子供体: 2
• LogD (pH = 5.5): 2.126404
• LogD (pH = 7.4): 2.1133182
• Log P: 2.1265736
• 摩尔折射率: 61.493 cm^3
• 极化性: 23.88337 Å^3
• 极化表面积: 58.56 Å^2
• 可自由旋转的化学键: 5
• 里宾斯基五规则: true

分子性质

理化性质

• 溶解度: DMSO; DMSO: ≥20 mg/mL
• 外观: white to off-white powder

安全信息

• 保存条件: -20°C
• 欧盟危险性物质标志: 有害性(Harmful) (Xn)
• 德国WGK号: 3
• 危险公开号: 22-37/38-41
• 安全公开号: 26-39
• GHS危险品标识: GHS05; GHS07
• GHS警示词: Danger
• GHS危险声明: H302-H315-H318-H335
• GHS警示性声明: P261-P280-P305 + P351 + P338
• 保存温度: 2-8°C

药理学性质

• 作用靶点: HDAC

产品相关信息

• 纯度: ≥98% (HPLC)
• 成盐信息: Free Base
• Empirical Formula (Hill Notation): C11H14ClNO3

详细说明

Selleck Chemicals - S1422

Research Area

• Description: Cancer

Biological Activity

• Description: Droxinostat (CMH, 5809354) is a selective inhibitor of HDAC3, HDAC6 and HDAC8 with IC50 of 16.9 μM, 2.47μM and 1.46 μM, respectively.
• Targets: HDAC3; HDAC6; HDAC8
• IC50: 16.9 μM; 2.47 μM; 1.46 μM ^[3]
• In Vitro: Droxinostat is originally identified as a sensitizer of PPC-1 cells to FAS and TRAIL by downregulating the expression of c-Fas-associated death domain-like interleukin-1-converting enzyme-like inhibitory protein (c-FLIP). ^[1]In PPC-1 cells cultured in suspension but not adherent conditions, Droxinostat (20 μM–60 μM) sensitizes cells to anoikis by initially activating caspase 8 with subsequent activation of the mitochondrial pathway. Similarly, Droxinostat also sensitizes other cancer cell lines including PC-3, DU-145, T47D, and OVCAR-3, but not LNCaP or MB-MDA-468, to anoikis or CH-11-induced apoptosis. ^[2]However, the direct targets of Droxinostat remains enigma until recently. It is revealed that in histone deacetylases (HDAC) isoform 1-10, Droxinostat selective inhibits HDAC3, 6, and 8, with IC50 values of 16.9 μM, 2.47 μM, and 1.46 μM, respectively, without inhibiting other HDAC members (IC50 > 20 μM). ^[3]In MCF-7 breast cancer cells, Droxinostat (10 μM–100 μM) sensitizes cells to apoptosis by decreasing c-FLIP_L and c-FLIP_S expression, reducing cell survival, and inducing apoptosis. ^[4]
• In Vivo: In SCID mice models, Droxinostat (30 μM)-treated PPC-1 cells results in decreased distant tumor formation than untreated cells. ^[2]
• Features: Droxinostat is a selective inhibitor of HDAC3, 6, and 8 and acts as a sensitizer to death receptor stimuli.

Protocol

• Protocol: Kinase Assay ^[3]
• HDAC Inhibition Assay: HDAC inhibition is assessed using the CycLex HDACs fluorometric assay according to the manufacturer's protocol and using crude nuclear extract from HeLa cells (principally HDAC1 and HDAC2). The relative activity is expressed as (fluorescence intensity of treated samples/fluorescence intensity of controls) × 100%.
• Protocol: Cell Assay ^[1]
• Cell Lines: PPC-1 cells
• Concentrations: 0–100 μM, dissolved in DMSO (final concentration of DMSO is 0.5%)
• Incubation Time: 24 hours
• Methods: PPC-1 cells (1 × 10^4) are seeded overnight into 96-well flat-bottomed plates in 100 μL of medium containing 2.5% FCS. The next day, Droxinostat is added. CH-11 antibody (100 ng/mL) is then added and the cells are incubated for 24 hours before assessing cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye reduction assay.
• Protocol: Animal Study ^[2]
• Animal Models: Male severe combined immunodeficient (SCID) mice models treated with PPC-1 cells
• Formulation: dsRed-PPC-1 cells that treated with Droxinostat (30 μM) or PBS buffer control are either injected via the tail vein or subcutaneously into the hind limbs

References

• References: [1] Schimmer AD, et al. Cancer Res, 2006, 66(4), 2367-2375.
• References: [2] Mawji IA, et al. J Natl Cancer Inst, 2007, 99(10), 811-822.
• References: [3] Wood TE, et al. Mol Cancer Ther, 2010, 9(1), 246-256.
• References: [4] Bijangi-Vishehsaraei K, et al. Mol Cell Biochem, 2010, 342(1-2), 133-142.

Sigma Aldrich - D6321

Biochem/physiol Actions
Droxinostat is a selective inhibitor of HDAC3, HDAC6, and HDAC8.

参考文献

• Schimmer AD, et al. Cancer Res, 2006, 66(4), 2367-2375.
• Mawji IA, et al. J Natl Cancer Inst, 2007, 99(10), 811-822.
• Wood TE, et al. Mol Cancer Ther, 2010, 9(1), 246-256.
• Bijangi-Vishehsaraei K, et al. Mol Cell Biochem, 2010, 342(1-2), 133-142.