Identification of KLHL12 Ligands Using Fragment-Based Methods
Alex G. Waterson·Stephen W. Fesik·Somnath Jana·Jianwen Cui·Kelvin Luong·Tyson A. Rietz·Ezequiel Alejandro Madrigal-Carrillo·Brian D. Lehmann·John Sensintaffar·Bin Zhao·Kangsa Amporndanai·Zoe A. Petros·W. Rush Scaggs·Selena Chacón Simon·Rakesh H. Vekariya·Kwangho Kim·Manikandan Thangaraj·Plamen P. Christov·Taylor M. South·Jiqing Sai·Anusha Thiruvaipati·Charles Schmidt·Rebecca Eells·William Moore·Edward T. Olejniczak·Jason Phan·Anish Vadukoot
Targeted protein degradation can be induced by recruiting a protein of interest to an E3 ligase, resulting in its ubiquitination and subsequent proteasome-mediated degradation. However, only a small number of E3 ligases have been utilized for degradation. Expansion of the repertoire of useful E3 ligases via the identification of ligands to those ligases could broaden the scope and applicability of the degradation paradigm. We have identified KLHL12 as an E3 ligase with higher expression in cance
