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Updated: Mar 2, 2026
10:28
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
Summary
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.
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