Imperial College London

The missing link between (un)druggable and degradable KRAS

by

Graphical abstract

A commentary on the first PROTAC that degrades KRas-G12C in cells

Professor Tate, Dr Elena De Vita, and Dr María Maneiro Rey were invited to introduce, to the broad audience of ACS Central Science, the recent findings on the first in cellulo active KRasG12C PROTAC developed by Crews laboratory (published in the same issue of ACS Central Science).

In this first reaction piece, the authors had the opportunity to take a step back and reflect on the status of both the PROTAC and the Ras GTPase targeting fields. Despite the undeniable substantial advancement in both areas, clear challenges are still foreseeable for researchers in the near future.

Questions surrounding the possibility of developing a non-covalent KRas PROTAC to target multiple malignant forms in cancer remain unanswered. In addition, the development of novel tools allowing for the straightforward design of effective PROTACs, thus reducing the current time required for optimization, are still required.

Reporter

Ravi Singh

Ravi Singh
Department of Chemistry