PHT-427

製品コードS1556 バッチS155601

化学情報

	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
* <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) is a dual Akt and PDPK1 inhibitor (high affinity binding for the PH domains of Akt and PDPK1) with K_i of 2.7 μM and 5.2 μM, respectively.
in vitro	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	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	Surface plasmon resonance (SPR) spectroscopy binding assays
キナーゼアッセイ	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 PHT-427.
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

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

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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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