PHT-427 化学構造
分子量: 409.61





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  • 研究分野
  • Combination Therapy



製品説明 PHT-427は一種のAktとPDPK1の二重抑制剤( AktとPDPK1のPHドメインが高い親和力を持っている)で、Ki値が2.7 μM and 5.2 μMに分かれます。
ターゲット 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]

プロトコル (参考用のみ)

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]

細胞株 Panc-1 cells
濃度 1-50 μM
実験の流れ 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
投与方法 Oral administration

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

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)
Body Surface Area (m2)0.0070.0250.
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)



Download PHT-427 SDF
分子量 409.61


CAS No. 1191951-57-1
保管 3年-20℃
2年-80℃in solvent
別名 CS-0223
溶解度 (25°C) * In vitro DMSO 82 mg/mL (200.19 mM)
Ethanol 60 mg/mL (146.48 mM)
Water <1 mg/mL
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

文献中の引用 (3)



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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID