Mariko Takahashi, Harrison B Chong, Siwen Zhang, Tzu-Yi Yang, Matthew J Lazarov, Stefan Harry, Michelle Maynard, Brendan Hilbert, Ryan D White, Heather E Murrey, Chih-Chiang Tsou, Kira Vordermark, Jonathan Assaad, Magdy Gohar, Benedikt R Dürr, Marianne Richter, Himani Patel, Gregory Kryukov, Natasja Brooijmans, Aliyu Sidi Omar Alghali, Karla Rubio, Antonio Villanueva, Junbing Zhang, Maolin Ge, Farah Makram, Hanna Griesshaber, Drew Harrison, Ann-Sophie Koglin, Samuel Ojeda, Barbara Karakyriakou, Alexander Healy, George Popoola, Inbal Rachmin, Neha Khandelwal, Jason R Neil, Pei-Chieh Tien, Nicholas Chen, Tobias Hosp, Sanne van den Ouweland, Toshiro Hara, Lillian Bussema, Rui Dong, Lei Shi, Martin Q Rasmussen, Ana Carolina Domingues, Aleigha Lawless, Jacy Fang, Satoshi Yoda, Linh Phuong Nguyen, Sarah Marie Reeves, Farrah Nicole Wakefield, Adam Acker, Sarah Elizabeth Clark, Taronish Dubash, John Kastanos, Eugene Oh, David E Fisher, Shyamala Maheswaran, Daniel A Haber, Genevieve M Boland, Moshe Sade-Feldman, Russell W Jenkins, Aaron N Hata, Nabeel M Bardeesy, Mario L Suvà, Brent R Martin, Brian B Liau, Christopher J Ott, Miguel N Rivera, Michael S Lawrence, Liron Bar-Peled
Cysteine-focused chemical proteomic platforms have accelerated the clinical development of covalent inhibitors for a wide range of targets in cancer. However, how different oncogenic contexts influence cysteine targeting remains unknown. To address this question, we have developed "DrugMap," an atlas of cysteine ligandability compiled across 416 cancer cell lines. We unexpectedly find that cysteine ligandability varies across cancer cell lines, and we attribute this to differences in cellular redox states, protein conformational changes, and genetic mutations...
April 17, 2024: Cell