PHT-427

製品コードS1556 バッチS155601

印刷

化学情報

Chemical Structure Synonyms CS-0223 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C20H31N3O2S2
分子量 409.61 CAS No. 1191951-57-1
Solubility (25°C)* 体外 DMSO 82 mg/mL (200.19 mM)
Ethanol 60 mg/mL (146.48 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 PHT-427 (CS-0223) は、Kiがそれぞれ2.7 μMおよび5.2 μMである二重AktおよびPDPK1阻害剤（AktとPDPK1のPHドメインに対する高親和性結合）です。
in vitro PH-427 is a pleckstrin homology domain inhibitor to Akt/PDPK1. This compound significantly reduces phospho-Ser241-PDPK1 phospho-Thr308-Akt in PC-3 prostate cancer cells at 10 μM, which shows that it could inhibit both Akt and PDPK1. It also inhibits translocation of the Akt and PDPK1 PH domains in plasma membrane. This chemical 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. It also shows antiproliferation in Panc-1 cells with IC50 of 65 μM.
in vivo PHT-427 shows great antitumor activity in BxPC-3 pancreatic, MCF-7 breast and A-549 NSCL cancer xenografts. This compound gives up to an 80% inhibition of tumor growth in BxPC-3 at doses of 125 to 250 mg/kg.

プロトコル(参考用のみ)

キナーゼアッセイ 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 細胞株 Panc-1 cells
濃度 1-50 μM
反応時間
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 this compound.
動物実験 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.
投薬量 125-250 mg/kg
投与方法 Oral administration

参考

  • http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2837366/
  • https://pubmed.ncbi.nlm.nih.gov/19491272/

カスタマーフィードバック

Data from [Data independently produced by Eur J Pharmacol, 2014, 747C, 71-87]

Data from [Blood, 2011, 118, 2840-2848]

Data from [Data independently produced by , , Research Letter, 2018, doi:org/10.1002/1873-3468.13305]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Functional restoration of lysosomes and mitochondria through modulation of AKT activity ameliorates senescence [ Exp Gerontol, 2023, 173:112091] PubMed: 36657533
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9] PubMed: 35868306
Telomerase RNA TERC and the PI3K-AKT pathway form a positive feedback loop to regulate cell proliferation independent of telomerase activity [ Nucleic Acids Res, 2022, gkac179] PubMed: 35323972
Identification of a New Antimicrobial Agent against Bovine Mastitis-Causing Staphylococcus aureus [ J Agric Food Chem, 2021, 10.1021/acs.jafc.1c02738] PubMed: 34406764
Patient-specific logic models of signaling pathways from screenings on cancer biopsies to prioritize personalized combination therapies. [ Mol Syst Biol, 2020, 16(2):e8664] PubMed: 32073727
Genipin, a natural AKT inhibitor, targets the PH domain to affect downstream signaling and alleviates inflammation [ Biochem Pharmacol, 2019, 170:113660] PubMed: 31605673
A natural AKT inhibitor swertiamarin targets AKT-PH domain, inhibits downstream signaling, and alleviates inflammation. [ FEBS J, 2019, 10.1111/febs.15112] PubMed: 31665825
The flavonoid baicalin improves glucose metabolism by targeting the PH domain of AKT and activating AKT/GSK3β phosphorylation. [ FEBS Lett, 2019, 593(2):175-186] PubMed: 30489635
A microfluidics platform for combinatorial drug screening on cancer biopsies. [ Nat Commun, 2018, 9(1):2434] PubMed: 29934552
Chlorogenic Acid Targeting of the AKT PH Domain Activates AKT/GSK3β/FOXO1 Signaling and Improves Glucose Metabolism. [ Nutrients, 2018, 10(10)] PubMed: 30249058

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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