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Telomerase_Rxiv.pdf (12.65 MB)

Targeted Covalent Inhibition of Telomerase

submitted on 22.07.2019 and posted on 23.07.2019 by Rick Betori, Yue Liu, Ding Wu, Rama Mishra, Scott Cohen, Stephen J. Kron, Karl Scheidt

Telomerase is a ribonuceloprotein complex responsible for maintaining telomeres and protecting chromosomal integrity. The human telomerase reverse transcriptase (hTERT) is expressed in ~90% of cancer cells where it confers the capacity for limitless proliferation. Along with its established role in telomere lengthening, telomerase also serves non-canonical extra-telomeric roles in oncogenic signaling, resistance to apoptosis, and enhanced DNA damage response. Here, we report a new class of natural product-inspired covalent inhibitors of telomerase that target the catalytic active site. We developed rationally designed probe compounds that modulate both the telomeric and extra-telomeric activities of telomerase and present new opportunities to investigate the diverse functions of this unique molecular machine.


NIGMS T32GM105538

NCI R01 CA217182


Email Address of Submitting Author


Northwestern University



ORCID For Submitting Author


Declaration of Conflict of Interest

A provisional composition of matter patent for NU-1 and related analogs has been filed.


Read the published paper

in ACS Chemical Biology

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