A patent update on PDK1 inhibitors (2015-present)
Simona Sestito1, Simona Rapposelli1
1a Department of Pharmacy , University of Pisa , Pisa , Italy.
Expert Opinion on Therapeutic Patents
|March 22, 2019
Summary
New PDK1 inhibitors targeting cancer pathways are emerging. Research focuses on novel strategies beyond ATP binding sites to block tumor growth and metastasis.
Area of Science:
- Biochemistry
- Medicinal Chemistry
- Oncology
Background:
- 3-Phosphoinositide-dependent kinase 1 (PDK1) is a master kinase in the AGC protein kinase family.
- PDK1 is implicated in cancer development, progression, metastasis, and chemoresistance.
Purpose of the Study:
- To review PDK1 inhibitors patented between October 2014 and December 2018.
- To classify these inhibitors based on chemical structure and inhibition type.
Main Methods:
- Literature review of patented PDK1 inhibitors.
- Classification of molecules by chemical structure and inhibition mechanism.
- Detailed discussion of specific examples within each class.
Main Results:
- A growing number of PDK1 inhibitors have been developed.
- Many new inhibitors target sites other than the ATP binding pocket, such as the PIF pocket or DFG-out conformation.
- Ongoing research explores innovative strategies like combination therapies and multitarget ligands.
Conclusions:
- PDK1 remains a significant target in cancer drug discovery.
- Novel inhibition strategies are being developed to overcome resistance and improve efficacy.
- Future research aims to block PDK1 and other critical tumor pathway proteins simultaneously.
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