A Malamitsi-Puchner

AM Slavotinek

BD Manning

C Parikh

J Andrae

J Iqbal

JD Carpten

JT Turner

K Sankhala

KE Landgraf

KS Kovacina

LG Biesecker

M Saleh

MJ Lindhurst

N Kohler

NN Danial

O Kaidanovich-Beilin

O Meyuhas

SPM Crouch

TR Fenton

Y Wang

Y Yu

Scientific Reports

AbstractA somatic activating mutation in AKT1, c.49G&gt;A, pGlu17Lys, that results in elevated AKT signaling in mutation-positive cells, is responsible for the mosaic overgrowth condition, Proteus syndrome. ARQ 092 is an allosteric pan-AKT inhibitor under development for treatment in cancer. We tested the efficacy of this drug for suppressing AKT signaling in cells and tissues from patients with Proteus syndrome. ARQ 092 reduced phosphorylation of AKT and downstream targets of AKT in a concentration-dependent manner in as little as two hours. While AKT signaling was suppressed with ARQ 092 treatment, cells retained their ability to respond to growth factor stimulation by increasing pAKT levels proportionally to untreated cells. At concentrations sufficient to decrease AKT signaling, little reduction in cell viability was seen. These results indicate that ARQ 092 can suppress AKT signaling and warrants further development as a therapeutic option for patients with Proteus syndrome.</jats:p

Marjorie J. Lindhurst

Miranda R. Yourick

Yi Yu

Ronald E. Savage

Dora Ferrari

Leslie G. Biesecker

Crossref

Repression of AKT signaling by ARQ 092 in cells and tissues from patients with Proteus syndrome

Repression of AKT signaling by ARQ 092 in cells and tissues from patients with Proteus syndrome

Abstract

Similar works

Full text

Available Versions

Crossref