Abstract
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 noncanonical extra-telomeric roles in oncogenic signaling, resistance to apoptosis, and enhanced DNA damage response. We report a new class of natural-product-inspired covalent inhibitors of telomerase that target the catalytic active site.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Sequence
-
Antineoplastic Agents / chemistry*
-
Antineoplastic Agents / pharmacology
-
Apoptosis / drug effects
-
Catalysis
-
Cell Line, Tumor
-
Cell Proliferation / drug effects
-
Cycloaddition Reaction
-
DNA Damage / drug effects
-
DNA-Binding Proteins / chemistry*
-
Diterpenes / chemistry*
-
Diterpenes / pharmacology
-
Drug Screening Assays, Antitumor
-
Enzyme Inhibitors / chemistry*
-
Enzyme Inhibitors / pharmacology
-
Humans
-
Models, Molecular
-
Molecular Structure
-
Protein Binding
-
Small Molecule Libraries / chemistry
-
Small Molecule Libraries / pharmacology
-
Structure-Activity Relationship
-
Telomerase / antagonists & inhibitors*
Substances
-
Antineoplastic Agents
-
DNA-Binding Proteins
-
Diterpenes
-
Enzyme Inhibitors
-
Small Molecule Libraries
-
chrolactomycin
-
Telomerase