Targeting PTEN using small molecule inhibitors.

Targeting PTEN using small molecule inhibitors.

Methods (San Diego, Calif.) (2015-03-10)

Lok Hang Mak, Rudiger Woscholski

ABSTRACT

PTEN (phosphatase and tensin homologue deleted on chromosome 10) is well known as a tumour suppressor. It's PI(3,4,5)P3 lipid phosphatase activity is an important counteracting mechanism in PI 3-kinase (phosphoinositide 3-kinase) signalling. Furthermore, PTEN lies upstream of Akt kinase, a key enzyme in insulin signalling regulating glucose uptake and cell growth. Therefore, PTEN has recently gained attention as a valuable drug target for the treatment of diabetes, stroke, cardiac infarct and fertility. This review summarizes the use of small molecules as PTEN inhibitors. Currently available methodologies and techniques for accessing PTEN inhibition in vitro and in cellulo will be discussed.

MATERIALS

Product Number

Brand

Product Description

D5545

Sigma-Aldrich

DL-Dithiothreitol, BioXtra, ≥99.0% (titration)

D0632

Sigma-Aldrich

DL-Dithiothreitol, ≥98% (HPLC), ≥99.0% (titration)

C7559

Sigma-Aldrich

Chloroform, ≥99%, PCR Reagent, contains amylenes as stabilizer

2104

Supelco

Hydrochloric acid solution, volumetric, 0.1 M HCl (0.1N), endotoxin free

A1343

Sigma-Aldrich

Ammonium molybdate, meets USP testing specifications

D6046

Sigma-Aldrich

Dulbecco′s Modified Eagle′s Medium - low glucose, With 1000 mg/L glucose, L-glutamine, and sodium bicarbonate, liquid, sterile-filtered, suitable for cell culture

D5671

Sigma-Aldrich

Dulbecco′s Modified Eagle′s Medium - high glucose, With 4500 mg/L glucose and sodium bicarbonate, without L-glutamine and sodium pyruvate, liquid, sterile-filtered, suitable for cell culture, suitable for hybridoma

02487

Supelco

Chloroform, analytical standard

17935

Supelco

Hydrogen chloride – methanol solution, ~1.25 m HCl (T), for GC derivatization, LiChropur^™

17934

Supelco

Hydrogen chloride – ethanol solution, ~1.25 M HCl, for GC derivatization, LiChropur^™

17933

Supelco

Hydrogen chloride – 2-propanol solution, ~1.25 M HCl (T), for GC derivatization, LiChropur^™

09878

Sigma-Aldrich

Ammonium molybdate tetrahydrate, BioUltra, ≥99.0% (T)

43819

Sigma-Aldrich

DL-Dithiothreitol, ≥99.0% (RT)

277908

Sigma-Aldrich

Ammonium molybdate, 99.98% trace metals basis

437581

Sigma-Aldrich

Chloroform, ACS reagent, ≥99.8%, contains 0.5-1.0% ethanol as stabilizer

480150

Sigma-Aldrich

Chloroform, ACS reagent, ≥99.8%, contains amylenes as stabilizer

84429

Sigma-Aldrich

Hydrochloric acid solution, ~6 M in H₂O, for amino acid analysis

T4174

Sigma-Aldrich

Trypsin-EDTA solution, 10 ×, sterile-filtered, BioReagent, suitable for cell culture, 5.0 g porcine trypsin and 2 g EDTA, 4Na per liter of 0.9% sodium chloride

M1019

Sigma-Aldrich

Ammonium molybdate tetrahydrate, BioReagent, suitable for cell culture, suitable for insect cell culture, 81.0-83.0% MoO₃ basis

132950

Sigma-Aldrich

Chloroform, ReagentPlus^®, ≥99.8%, contains 0.5-1.0% ethanol as stabilizer

30721

Sigma-Aldrich

Hydrochloric acid, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., fuming, ≥37%, APHA: ≤10

294837

Sigma-Aldrich

Hydrogen chloride solution, 1.0 M in diethyl ether