PHT-427 化学構造
分子量: 409.61

品質と確認

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Quality Control & MSDS

製品情報

  • Combination Therapy
    併用療法
  • Compare Akt Inhibitors
    Akt阻害剤を比較
  • 研究分野

製品の説明

生物活性

情報 PHT-427は、二重AktとPDPK1阻害剤で、Ki が それぞれ2.7 μM と 5.2 μMです。
目標 Akt PDPK1
IC50 2.7 μM 5.2 μM [1]
In vitro試験 PH-427 is a pleckstrin homology domain inhibitor to Akt/PDPK1. PH-427 significantly reduces phospho-Ser241-PDPK1 phospho-Thr308-Akt in PC-3 prostate cancer cells at 10 μM, which shows that PHT-427 could inhibit both Akt and PDPK1. PHT-427 also inhibits translocation of the Akt and PDPK1 PH domains in plasma membrane. [1] PHT-427 induces apoptosis and inhibits AKT phosphorylation with IC50 of 8.6 μM (in BxPC-3 cells), which mainly on its Ser473 residue and less strongly on Thr308 residue without affecting total Akt protein expression. PHT-427 also shows antiproliferation in Panc-1 cells with IC50 of 65 μM. [2]
In vivo試験 PHT-427 shows great antitumor activity in BxPC-3 pancreatic, MCF-7 breast and A-549 NSCL cancer xenografts. PHT-427 gives up to an 80% inhibition of tumor growth in BxPC-3 at doses of 125 to 250 mg/kg. [1]
臨床試験
特集

推薦された実験操作 (公開の文献だけ)

キナーゼアッセイ: [1]

Surface plasmon resonance (SPR) spectroscopy binding assays All interaction analyses are performed with a Biacore 2000, Biacore 2000 Control Software v3.2, and BIAevaluation v4.1 analysis software. The PH domain GST-fusion proteins (Akt1, IRS1, and PDK1) are immobilized on a CM5 Sensorchip using Biacore's Amine Coupling Kit to a level of 10,000 Response units (RUs). Small molecule analytes at concentrations ranging from 0.1 to 10 × the predicted KD are injected at a high flow rate (30μL/min). DMSO concentrations in all samples and running buffer are 1% (v/v) or less.

細胞アッセイ: [2]

細胞系 Panc-1 cells
濃度 1-50 μM
処理時間
方法 Cell growth inhibition is determined using a micro-cytoxicity assay. Cells are plated in 96-well micro-cytoxicity at 5-10 × 103 cells per well (depending on cell doubling time) and grown for 7 days. PHT-427 dissolved in DMSO is added directly to the media, at various concentrations ranging from 1 to 50 μM. The endpoint is spectrophotometric determination of the protein content of each well using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. A concentration-response relationship at two or more concentration levels is used to obtain an IC50 for PHT-427.

動物実験: [1]

動物モデル BxPC-3, Panc-1, MiaPaCa-2, PC-3, SKOV-3, A-549 or MCF-7 cells are injected subcutaneously into the flanks of female scid mice.
製剤 40 to 50 mg/mL in sesame seed oil
投薬量 125-250 mg/kg
管理 Oral administration
Solubility 5% DMSO/95% Corn oil, 5 mg/mL
* 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.

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

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
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 PHT-427 SDF
分子量 409.61
化学式

C20H31N3O2S2

CAS No. 1191951-57-1
保管 2年-20℃
6月-80℃in DMSO
別名 CS-0223
溶解度 (25°C) * In vitro DMSO 82 mg/mL (200 mM)
<1 mg/mL (<1 mM)
エタノール 60 mg/mL (146 mM)
In vivo 5% DMSO/95% Corn oil, 5 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-dodecyl-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide

研究分野

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Rating
Source Blood, 2011, 118, 2840-2848. PHT-427 purchased from Selleck
Method Luciferase reporter assays
Cell Lines 32D cells, BCR-ABL cells
Concentrations 20 μM
Incubation Time 24 h
Results Treatment of 32D/BCR-ABL cells withthe AKT/PDPK1 inhibitor PHT-427, the PI3K inhibitor LY294002 or the BCR-ABL inhibitor imatinib substantially reduced Atf5 promoter-directed luciferase activity.

製品表彰状 (1)

技術サポート&よくある質問(FAQ)

顧客がするかもしれない質問に対する答えは、指示を取り扱っている阻害剤で見つかります。話題は、貯蔵液(阻害剤と特別な注意を細胞ベースの分析法と動物のために必要とする問題を保存することは実験します)を準備する方法を含みます。

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