Screening for novel chemical scaffolds targeting PCNA identifies the Hsp90alpha inhibitor SNX-2112.

Jennifer Jossart¹, Ning Ma², Pouya Haratipour¹, Caroline M Li³, Christopher Jang³, Long Gu³, Terrence E O'Brien⁴, Nagarajan Vaidehi², Linda H Malkas³, Robert J Hickey¹, J Jefferson P Perry¹

¹Department of Cancer Biology and Molecular Medicine, City of Hope Medical Center, Monrovia, CA, USA.

²Department of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA, 91010, USA.

³Department of Molecular Diagnostics and Experimental Therapeutics, City of Hope Medical Center, Monrovia, CA, USA.

⁴Atomwise, Inc. San Francisco, CA, USA.

PubMed PMC DOI PDF

Abstract

Proliferating cell nuclear antigen (PCNA) protein is an emerging therapeutic target for several diseases including cancers, and certain viral infections. It was previously regarded as being undruggable, due to its functions as a molecular hub that regulates a multitude of essential cellular pathways. However, we recently developed a PCNA inhibitor, AOH1996, which acts as a molecular glue between P…

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