Discovery of Novel AKT Inhibitors with Enhanced Anti-Tumor Effects in Combination with the MEK Inhibitor

Safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity of the oral AKT inhibitor GSK2141795 (GSK795) in a phase I first-in-human study.

(2017) H. A. Burris et al.   JOURNAL OF CLINICAL ONCOLOGY

Targeting Activated Akt with GDC-0068, a Novel Selective Akt Inhibitor That Is Efficacious in Multiple Tumor Models

(2013) J. Lin et al.   CLINICAL CANCER RESEARCH

Development of PI3K inhibitors: lessons learned from early clinical trials

(2013) Jordi Rodon et al.   Nature Reviews Clinical Oncology

PI3K regulates MEK/ERK signaling in breast cancer via the Rac-GEF, P-Rex1

(2013) H. Ebi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

TORC1 Suppression Predicts Responsiveness to RAF and MEK Inhibition in BRAF-Mutant Melanoma

(2013) R. B. Corcoran et al.   Science Translational Medicine

mTORC1 Inhibition Is Required for Sensitivity to PI3K p110  Inhibitors in PIK3CA-Mutant Breast Cancer

(2013) M. Elkabets et al.   Science Translational Medicine

MEK Inhibition Leads to PI3K/AKT Activation by Relieving a Negative Feedback on ERBB Receptors

(2012) A. B. Turke et al.   CANCER RESEARCH

Therapeutic potential of MEK inhibition in acute myelogenous leukemia: rationale for “vertical” and “lateral” combination strategies

(2012) Maria Rosaria Ricciardi et al.   JOURNAL OF MOLECULAR MEDICINE-JMM

Preclinical Pharmacology of AZD5363, an Inhibitor of AKT: Pharmacodynamics, Antitumor Activity, and Correlation of Monotherapy Activity with Genetic Background

(2012) B. R. Davies et al.   MOLECULAR CANCER THERAPEUTICS

AKT Inhibition Relieves Feedback Suppression of Receptor Tyrosine Kinase Expression and Activity

(2011) Sarat Chandarlapaty et al.   CANCER CELL

GSK1120212 (JTP-74057) Is an Inhibitor of MEK Activity and Activation with Favorable Pharmacokinetic Properties for Sustained In Vivo Pathway Inhibition

(2011) A. G. Gilmartin et al.   CLINICAL CANCER RESEARCH

First-in-Man Clinical Trial of the Oral Pan-AKT Inhibitor MK-2206 in Patients With Advanced Solid Tumors

(2011) Timothy A. Yap et al.   JOURNAL OF CLINICAL ONCOLOGY

A Mosaic Activating Mutation inAKT1Associated with the Proteus Syndrome

(2011) Marjorie J. Lindhurst et al.   NEW ENGLAND JOURNAL OF MEDICINE

PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2-overexpressing breast cancer

(2011) V Serra et al.   ONCOGENE

An Activating Mutation of AKT2 and Human Hypoglycemia

(2011) K. Hussain et al.   SCIENCE

Crystal Structure of Human AKT1 with an Allosteric Inhibitor Reveals a New Mode of Kinase Inhibition

(2010) Wen-I Wu et al.   PLoS One

The oncogenic mutation in the pleckstrin homology domain of AKT1 in endometrial carcinomas

(2009) K Shoji et al.   BRITISH JOURNAL OF CANCER

Basal Subtype and MAPK/ERK Kinase (MEK)-Phosphoinositide 3-Kinase Feedback Signaling Determine Susceptibility of Breast Cancer Cells to MEK Inhibition

(2009) O. K. Mirzoeva et al.   CANCER RESEARCH

In vivo Antitumor Activity of MEK and Phosphatidylinositol 3-Kinase Inhibitors in Basal-Like Breast Cancer Models

(2009) K. P. Hoeflich et al.   CLINICAL CANCER RESEARCH

Combination of EGFR and MEK1/2 inhibitor shows synergistic effects by suppressing EGFR/HER3-dependent AKT activation in human gastric cancer cells

(2009) Y.-K. Yoon et al.   MOLECULAR CANCER THERAPEUTICS

Identifying genotype-dependent efficacy of single and combined PI3K- and MAPK-pathway inhibition in cancer

(2009) M. L. Sos et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Differential induction of apoptosis in HER2 and EGFR addicted cancers following PI3K inhibition

(2009) A. C. Faber et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A novel AKT3 mutation in melanoma tumours and cell lines

(2008) M A Davies et al.   BRITISH JOURNAL OF CANCER

Characterization of an Akt Kinase Inhibitor with Potent Pharmacodynamic and Antitumor Activity

(2008) N. Rhodes et al.   CANCER RESEARCH

PI3K pathway alterations in cancer: variations on a theme

(2008) T L Yuan et al.   ONCOGENE