A new molecule holds promise for cancer and rare diseases

Researchers at the University of California, Irvine and the Italian Institute of Technology have developed a new molecule, ALY101, that targets a variety of tumor cells and mice with a common type of melanoma The model shows promising anticancer activity

The collaboration of Dr.

Their work initially focused on blocking the interaction of members of the CDC42 family of GTPases with the key kinase PAK1, which is amplified in breast, colon and other cancers, and in the pathology of rare diseases such as neurofibromatosis and Ewing's sarcoma active

"We discovered a previously unknown PAK1-binding pocket, present only in CDC42, and we used this pocket at the interface between the two proteins to disrupt the interaction that normally leads to PAK1 activation

Specifically, the lead compound discovered in the collaboration, ALY101, works by blocking the interaction, which normally converts PAK1 from an inactive state to an active state

This rational approach to structure-based drug design has been fully integrated with the wet bioanalytical workflow of the UCI Ghanaian laboratory

"This compound and the drug's effects on tumors and their microenvironment have potential applications, either as a monotherapy or as a combination therapy to reduce the dose-limiting toxicity of existing drugs, or as an anti-cancer drug," Garnerson said.

This research was supported by funding from foundations such as the Italian Association for Cancer Research and the National Institutes of Health, including NIH awards R01CA244571 and U54CA217378

Alyra's lead project, ALY101, grew out of this work and works to restore normal cell signaling processes that may become compromised in patients with certain cancers and rare diseases such as neurofibromatosis type 2 exception

"We are very pleased to see the work of Dr.