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  2. PI3K/Akt/mTOR Apoptosis
  3. Akt Apoptosis
  4. PHT-427

PHT-427 是一種 Akt 和 PDPK1 雙重抑制劑，與 Akt 和 PDPK1 中的 PH 結(jié)構(gòu)域有親和性，Ki 分別為 2.7 μM 和 5.2 μM。

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PHT-427 Chemical Structure

PHT-427 Chemical Structure

CAS No. : 1191951-57-1

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規(guī)格 價格 是否有貨 數(shù)量
Free Sample (0.1 - 0.2 mg)   Apply now  
10 mM * 1 mL in DMSO ￥550
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5 mg ￥312
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10 mg ￥500
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50 mg ￥1900
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100 mg ￥3200
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200 mg ￥5500
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500 mg   詢價  
1 g   詢價  

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MCE 顧客使用本產(chǎn)品發(fā)表的 1 篇科研文獻

查看 Akt 亞型特異性產(chǎn)品:

  • 生物活性

  • 實驗參考方法

  • 純度 & 產(chǎn)品資料

  • 參考文獻

生物活性

PHT-247 is an inhibitor of the pleckstrin homology (PH) domain of Akt, and it is also an inhibitor of PDPK1 with Kis of 2.7 μM and 5.2 μM and for Akt and PDPK1, respectively.

IC50 & Target[1]

PDPK1

5.2 μM (Ki)

細胞效力
(Cellular Effect)
Cell Line Type Value Description References
BXPC-3 IC50
57 μM
Compound: 29
Cytotoxicity against human BxPC3 cells by MTT assay
Cytotoxicity against human BxPC3 cells by MTT assay
[PMID: 21353784]
BXPC-3 IC50
6.3 μM
Compound: 14
Inhibition of Akt phosphorylation in human BxPC3 cells by Western blotting
Inhibition of Akt phosphorylation in human BxPC3 cells by Western blotting
[PMID: 19734051]
體外研究
(In Vitro)

The effects of PHT-427 on cell signaling are investigated by RPPA using a panel of 86 antibodies to phospho- and non-phosphorylated signaling protein related to PtdIns-3-K/PDPK1/Akt signaling in PC-3 prostate cells where PtdIns-3-K/PDPK1/Akt signaling is activated because of homozygous PTEN mutation. After 16 hours, a reduction is observed in phospho-Ser241-PDPK1 phospho-Thr308-Akt by both 10 μM PH-427 and 0.1 μM Wortmannin. Finally, phospho-Ser657-protein kinase C (PKC) and total SGK1 are decreased by treatment with both PHT-427 and Wortmannin. These results suggest that at 10 μM PHT-427 inhibits both Akt and PDKP1. The BxPC-3 and MiaPaCa-2 pancreatic cancer cell lines are probed by Western blotting following up to 24 hr exposure to 10 μM PHT-427, which is below the IC50 for cell growth inhibition of around 30 μM, to determine the effects of PHT-427 on of the PtdIns-3-K/PDPK1/Akt signaling pathway components[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
體內(nèi)研究
(In Vivo)

Mice with BxPC-3 pancreatic, MCF-7 breast or A-549 NSCL cancer xenografts are administered PHT-427, or its analogs with a C-4, C-6 or C-8 alkyl chain by oral gavage twice a day for 10 days. The results show that PHT-427 has the greatest antitumor activity with the C-8 chain analog having less activity, and analogs with a C-4 or C-6 chain very little activity. All further antitumor studies are conducted using compound PHT-427. Plasma levels of PHT-427 following oral administration to mice of a dose of 200 mg/kg show rapid absorption, without a lag phase, Cmax is 8.2 μg/mL 1 hr following dosing, and the elimination half-life is 1.4 hr with a terminal PHT-427 concentration of 0.1 μg/mL 10 hr after dosing. The plasma concentration of PH-427 is above the level which gave inhibition of Akt and PDPK1 signaling in cells of 10 μM (4 μg/mL) for at least 3 hr[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
分子量

409.61

Formula

C20H31N3O2S2
CAS 號
性狀

固體

顏色

White to off-white

運輸條件

Room temperature in continental US; may vary elsewhere.
儲存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
溶解性數(shù)據(jù)
細胞實驗： 

DMSO 中的溶解度 : 25 mg/mL (61.03 mM; 超聲助溶; 吸濕的 DMSO 對產(chǎn)品的溶解度有顯著影響，請使用新開封的 DMSO)

配制儲備液
濃度 溶劑體積 質(zhì)量 1 mg 5 mg 10 mg
1 mM 2.4413 mL 12.2067 mL 24.4135 mL
5 mM 0.4883 mL 2.4413 mL 4.8827 mL
查看完整儲備液配制表

* 請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；一旦配成溶液，請分裝保存，避免反復凍融造成的產(chǎn)品失效。
儲備液的保存方式和期限：-80°C, 2 years; -20°C, 1 year。-80°C儲存時，請在2年內(nèi)使用， -20°C儲存時，請在1年內(nèi)使用。

  • 摩爾計算器

  • 稀釋計算器

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

質(zhì)量
=
濃度
×
體積
×
分子量 *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

濃度 (start)

C1

×
體積 (start)

V1

=
濃度 (final)

C2

×
體積 (final)

V2

動物實驗：

請根據(jù)您的 實驗動物和給藥方式 選擇適當?shù)娜芙夥桨浮?

以下溶解方案都請先按照 In Vitro 方式配制澄清的儲備液，再依次添加助溶劑：
——為保證實驗結(jié)果的可靠性，澄清的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的工作液，建議您現(xiàn)用現(xiàn)配，當天使用；
以下溶劑前顯示的百分比是指該溶劑在您配制終溶液中的體積占比；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的方式助溶

  • 方案 一

    請依序添加每種溶劑： 10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (6.10 mM); 澄清溶液

    此方案可獲得 ≥ 2.5 mg/mL（飽和度未知）的澄清溶液。

    以 1 mL 工作液為例，取 100 μL 25.0 mg/mL 的澄清 DMSO 儲備液加到 400 μL PEG300 中，混合均勻；再向上述體系中加入 50 μL Tween-80，混合均勻；然后再繼續(xù)加入 450 μL 生理鹽水 定容至 1 mL。

    生理鹽水的配制：將 0.9 g 氯化鈉，溶解于 ddH?O 并定容至 100 mL，可以得到澄清透明的生理鹽水溶液。
  • 方案 二

    請依序添加每種溶劑： 10% DMSO    90% Corn Oil

    Solubility: ≥ 2.5 mg/mL (6.10 mM); 澄清溶液

    此方案可獲得 ≥ 2.5 mg/mL（飽和度未知）的澄清溶液，此方案實驗周期在半個月以上的動物實驗酌情使用。

    以 1 mL 工作液為例，取 100 μL 25.0 mg/mL 的澄清 DMSO 儲備液加到 900 μL玉米油中，混合均勻。

動物溶解方案計算器
請輸入動物實驗的基本信息：

給藥劑量

mg/kg

動物的平均體重

g

每只動物的給藥體積

μL

動物數(shù)量

只
由于實驗過程有損耗，建議您多配一只動物的量
請輸入您的動物體內(nèi)配方組成：
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
如果您的動物是免疫缺陷鼠或者體弱鼠，建議 DMSO 中的在最后工作液體系中的占比盡量不超過 2%。
方案所需 助溶劑 包括：DMSO， ，均可在 MCE 網(wǎng)站選購。 ，Tween 80，均可在 MCE 網(wǎng)站選購。
計算結(jié)果
工作液所需濃度 : mg/mL
儲備液配制方法 : mg 藥物溶于 μL  DMSO（母液濃度為 mg/mL）。
您所需的儲備液濃度超過該產(chǎn)品的實測溶解度，以下方案僅供參考，如有需要，請與 MCE 中國技術(shù)支持聯(lián)系。
動物實驗體內(nèi)工作液的配制方法 : 取 μL DMSO 儲備液，加入 μL 。 μL ，混合均勻至澄清，再加 μL Tween 80，混合均勻至澄清，再加 μL 生理鹽水。
連續(xù)給藥周期超過半月以上，請謹慎選擇該方案。
請確保第一步儲備液溶解至澄清狀態(tài)，從左到右依次添加助溶劑。您可采用超聲加熱 （超聲清洗儀，建議頻次 20-40 kHz），渦旋吹打等方式輔助溶解。
純度 & 產(chǎn)品資料
參考文獻
Cell Assay
[1]

Panc-1 cells stably transfected with green fluorescent protein (GFP) tagged Akt or PDKP1 PH domains are serum starved in phenol red free growth medium on glass-bottom 96-well imaging plates for 16 hours. They are then treated with PHT-427 at 1, 5, and 10 μM or PI-103 for 4 hr, and stimulated with 50 ng/mL IGF-1 for 10 min. Images are taken before and after IGF-1 treatment using an IN Cell Analyzer 1000 instrument with a Nikon Plan Fluor ELWD 20X/0.45 objective loaded and using a 300msec exposure time[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[1]

Mice[1]
Female C57Bl/6 mice are administered PHT-427 as a single oral dose of 200 mg/kg. The mice are killed at different times (3 mice at each time point), blood collected into heparinized tubes and plasma prepared and stored frozen at -80°C. For assay 0.2 mL plasma is mixed with 0.2 mL of 0.1 M sodium phosphate buffer, pH 4.0, and extracted for 1 hr by inversion with 1 ml ethyl acetate. After centrifugation 0.8 mL of the organic layer is removed, evaporated under N2 and redissolved in 0.2 mL ethanol and 10 μL injected onto a Waters Quattro Ultima tandem mass spectrometer using a Phenomenex Luna 3.0 μm, 2.0×50 mm C8 analytical column with detection and quantification by multiple reaction monitoring with the mass spectrometer operating in electrospray positive ionization mode.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
參考文獻

完整儲備液配制表

* 請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；一旦配成溶液，請分裝保存，避免反復凍融造成的產(chǎn)品失效。
儲備液的保存方式和期限：-80°C, 2 years; -20°C, 1 year。-80°C儲存時，請在2年內(nèi)使用， -20°C儲存時，請在1年內(nèi)使用。

可選溶劑 濃度 溶劑體積 質(zhì)量 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.4413 mL 12.2067 mL 24.4135 mL 61.0337 mL
5 mM 0.4883 mL 2.4413 mL 4.8827 mL 12.2067 mL
10 mM 0.2441 mL 1.2207 mL 2.4413 mL 6.1034 mL
15 mM 0.1628 mL 0.8138 mL 1.6276 mL 4.0689 mL
20 mM 0.1221 mL 0.6103 mL 1.2207 mL 3.0517 mL
25 mM 0.0977 mL 0.4883 mL 0.9765 mL 2.4413 mL
30 mM 0.0814 mL 0.4069 mL 0.8138 mL 2.0345 mL
40 mM 0.0610 mL 0.3052 mL 0.6103 mL 1.5258 mL
50 mM 0.0488 mL 0.2441 mL 0.4883 mL 1.2207 mL
60 mM 0.0407 mL 0.2034 mL 0.4069 mL 1.0172 mL
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產(chǎn)品名稱：
PHT-427
目錄號：
HY-12063
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