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Discovery of a Small Molecule Probe to Rpn-6, an Essential Subunit of the 26S Proteasome

submitted on 15.11.2019, 18:08 and posted on 25.11.2019, 16:34 by Wenzhi Tian, Darci Trader
Rpn-6 is among several essential proteins that facilitate assembly of the 26S proteasome. We were interested in discovering a small molecule binder to Rpn-6 that could be used to further our understanding of the association of the 19S regulatory particle with the 20S core particle and if a small molecule-Rpn-6 interaction could potentially be cytotoxic to cancer cells that heavily rely on proteasome activity for survival. A workflow to utilize a one-bead-one-compound library and a thermal shift assay was developed to discover such a molecule. TXS-8 was discovered to have low micromolar range binding affinity for Rpn-6 and showed with very limited binding to other proteins. Cytotoxicity of TXS-8 was evaluated in several cell lines, revealing increased cytotoxicity to hematological cancers.


Email Address of Submitting Author


Purdue University



ORCID For Submitting Author


Declaration of Conflict of Interest

No conflict of interest.


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