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Updated: Mar 2, 2026

A Semi-High-Throughput Adaptation of the NADH-Coupled ATPase Assay for Screening Small Molecule Inhibitors
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A Semi-High-Throughput Adaptation of the NADH-Coupled ATPase Assay for Screening Small Molecule Inhibitors

Published on: August 17, 2019

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Recent progress towards clinically relevant ATP-competitive Akt inhibitors

Bayard R Huck1, Igor Mochalkin1

  • 1Discovery Technologies, Global Research & Development, Merck KGaA, Darmstadt, Germany.

Bioorganic & Medicinal Chemistry Letters
|May 17, 2017
PubMed

Insights

The PI3K/Akt/mTOR (PAM) pathway is frequently mutated in cancers. New Akt inhibitors show promise for improved cancer treatment, with several in clinical development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Medicinal Chemistry

Background:

  • The PI3K/Akt/mTOR (PAM) pathway is frequently altered in human cancers.
  • Limited clinical success of mTOR inhibitors necessitates novel therapeutic strategies.
  • Akt represents a key signaling node within the PAM pathway for targeted inhibition.

Purpose of the Study:

  • To explore the druggability of the PAM pathway.
  • To identify improved targets for PAM pathway inhibition beyond mTOR.
  • To review medicinal chemistry efforts and clinical development of Akt inhibitors.

Main Methods:

  • Review of medicinal chemistry literature.
  • Analysis of preclinical data for Akt inhibitors.
  • Summary of ongoing clinical trials for Akt-targeting agents.

Main Results:

  • Identification of multiple ATP-competitive Akt inhibitors.
  • Preclinical data supporting the efficacy of Akt inhibitors.
  • Several Akt inhibitors are currently in clinical development.

Conclusions:

  • Akt is a promising target for cancer therapy, particularly in tumors with Akt1 mutations.
  • Medicinal chemistry has yielded potent Akt inhibitors.
  • Ongoing clinical trials will determine the therapeutic benefit of these novel agents.
Keywords:
Akt inhibitorClinical candidateKinase inhibitorPI3K/Akt/mTOR pathway

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