- Title Information
- Title
- Discovery and Characterization of AP Endonuclease 1 Small Molecule Inhibitors: Impact on DNA Repair and Cancer Cell Viability
- Type of Resource (primo)
- dissertations
- Name:
Personal
- Name Part
- Wu, Hongmei
- Role
- Role Term:
Text
- creator
- Name:
Personal
- Name Part
- Sobol, Robert
- Role
- Role Term:
Text
- Advisor
- Name:
Personal
- Name Part
- Roos, Wynand
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Horrigan, Diana
- Role
- Role Term:
Text
- Reader
- Name:
Corporate
- Name Part
- Brown University. Biology and Medicine: Biotechnology
- Role
- Role Term:
Text
- sponsor
- Origin Information
- Copyright Date
- 2026
- Physical Description
- Extent
- ix, 54 p.
- digitalOrigin
- born digital
- Note:
thesis
- Thesis (Sc. M.)--Brown University, 2026
- Genre (aat)
- theses
- Abstract
- Apurinic/Apyrimidinic Endonuclease 1 (APE1) is a multifunctional protein that plays critical roles in base excision repair (BER), redox regulation of transcription factors, and RNA processing. APE1 is frequently overexpressed in diverse cancer types, where it contributes to tumor progression, therapeutic resistance, and poor clinical outcomes by enhancing DNA repair capacity and activating oncogenic signaling pathways. Accordingly, small-molecule APE1 inhibitors have emerged as promising agents to re-sensitize cancer cells to DNA-damaging chemotherapies, including temozolomide (TMZ). Despite this potential, the mechanisms of action of many reported APE1 inhibitors and their direct effects on DNA repair remain incompletely understood.
In this study, we systematically characterized five commercially available small-molecule APE1 inhibitors and performed compound screening to identify novel candidates using a newly developed DNA Repair Molecular Beacon (DRMB) assay. Using this approach, we demonstrate that E3330, previously characterized as a selective inhibitor of APE1 redox (Ref-1) activity, also potently inhibits APE1 AP endonuclease function. Furthermore, we show that E3330 disrupts BER by suppressing Poly (ADP-ribose) polymerase (PARP) activation and enhances sensitivity to alkylating agents. Together, these findings reveal an unanticipated dual mechanism of E3330 and underscore the utility of the DRMB assay for identifying and mechanistically characterizing APE1 inhibitors with therapeutic potential.
- Subject (fast)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/00886599")
- Topic
- DNA repair
- Subject
- Topic
- Novel anti-cancer small molecules
- Subject
- Topic
- APE1
- Language
- Language Term (ISO639-2B)
- English
- Record Information
- Record Content Source (marcorg)
- RPB
- Record Creation Date
(encoding="iso8601")
- 20260516