Droxinostat 化学構造
分子量: 243.69

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Quality Control & MSDS

製品説明

  • Compare HDAC Inhibitors
    HDAC製品生物活性の比較
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  • Combination Therapy
    併用療法

製品の説明

生物活性

製品説明 DroxinostatはHDAC3、HDAC6とHDAC8の選択的な阻害剤で、 IC50 が 1.46 μM から 16.9 μMまで。
ターゲット HDAC3 HDAC6 HDAC8
IC50 16.9 μM 2.47 μM 1.46 μM [3]
In vitro試験 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-FLIPL and c-FLIPS expression, reducing cell survival, and inducing apoptosis. [4]
In vivo試験 In SCID mice models, Droxinostat (30 μM)-treated PPC-1 cells results in decreased distant tumor formation than untreated cells. [2]
臨床試験
特集 Selective inhibitor of HDAC3, HDAC6,and HDAC8.

プロトコル (参考用のみ)

キナーゼアッセイ: [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

細胞アッセイ: [1]

細胞株 PPC-1 cells
濃度 0–100 μM, dissolved in DMSO (final concentration of DMSO is 0.5%)
反応時間 24 hours
実験の流れ PPC-1 cells (1 × 104) 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.

動物実験: [2]

動物モデル Male severe combined immunodeficient (SCID) mice models treated with PPC-1 cells
製剤 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
投薬量
投与方法

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download Droxinostat SDF
分子量 243.69
化学式

C11H14ClNO3

CAS No. 99873-43-5
保管 2年-20℃
6月-80℃in solvent
別名 NS 41080
溶解度 (25°C) * In vitro DMSO 49 mg/mL (201.07 mM)
エタノール 49 mg/mL (201.07 mM)
<1 mg/mL (<1 mM)
In vivo 30% propylene glycol, 5% Tween 80, 65% D5W 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
化学名 4-(4-chloro-2-methylphenoxy)-N-hydroxybutanamide

カスタマーフィードバック (2)


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Rating
Source PLoS One, 2014, 9(8), e102684. Droxinostat purchased from Selleck
Method Microfluidic lab-on-a-chip assay
Cell Lines 2D10 cells
Concentrations 2 uM
Incubation Time 24 h
Results Droxinostat (2 uM) was used to inhibit HDAC3 activity after depletion of HDAC1, -2, or -3. Again, depletion of HDAC1 or -2 with inhibition of HDAC3 did not increase the percent of cells with LTR driven GFP protein expression observed over Droxinostat treatment of the cells transduced with the scrambled shRNA. However, inhibiting the enzymatic activity of the remaining HDAC3 enzyme with Droxinostat following HDAC3 depletion induced a significant increase in the percent of cells expressing GFP protein from the HIV-1 LTR compared to cells that were transduced with the scrambled control and treated with Droxinostat.

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Rating
Source Dr. Zhang of Tianjin Medical University. Droxinostat purchased from Selleck
Method Western blot
Cell Lines Breast cancer cells line T47D
Concentrations 0.01-10 μM
Incubation Time
Results Droxinostat treatment resulted in a reduction of Histone H3 acetylation in T47D cells.

文献中の引用 (5)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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