Small Molecules Targeting DNA Polymerase Theta (POLθ) as Promising Synthetic Lethal Agents for Precision Cancer Therapy
Sign Up to like & getrecommendations! Published in 2023 at "Journal of Medicinal Chemistry"
DOI: 10.1021/acs.jmedchem.2c02101
Abstract: Synthetic lethality (SL) is an innovative strategy in targeted anticancer therapy that exploits tumor genetic vulnerabilities. This topic has come to the forefront in recent years, as witnessed by the increased number of publications since… read more here.
Keywords: polymerase; dna polymerase; polymerase theta; therapy ... See more keywords
Preparation of Substituted Heterocycles and Their Use as DNA Polymerase Theta (POLQ) Inhibitors.
Sign Up to like & getrecommendations! Published in 2025 at "ACS medicinal chemistry letters"
DOI: 10.1021/acsmedchemlett.5c00137
Abstract: DNA polymerase theta (POLQ) is a member of the DNA polymerase family and plays an important role in DNA damage repair. The present patent discloses a series of substituted heterocycles and their use as potent… read more here.
Keywords: heterocycles use; dna polymerase; substituted heterocycles; polymerase ... See more keywords
ADH5/ALDH2 dehydrogenases and DNA polymerase theta protect normal and malignant hematopoietic cells from formaldehyde challenge: therapeutic implications
Sign Up to like & getrecommendations! Published in 2025 at "Leukemia"
DOI: 10.1038/s41375-025-02687-3
Abstract: Normal hematopoietic stem and progenitor cells (HSPCs) are exposed to physiological levels of formaldehyde but occasionally may be challenged by high levels of formaldehyde generated by endogenous and exogenous sources. In addition, leukemia cells stressed… read more here.
Keywords: dna polymerase; adh5 aldh2; pol; polymerase theta ... See more keywords
Abstract A107: Development of polymerase theta inhibitors for precision medicine in BRCA-deficient cancers
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DOI: 10.1158/1535-7163.targ-17-a107
Abstract: DNA polymerase theta (Polq) is important for the proliferation of BRCA-deficient cancer cells, but is dispensable for normal cell growth. Thus, Polq is widely considered to be an important new drug target for BRCA-deficient cancers,… read more here.
Keywords: medicine; brca deficient; polymerase theta; deficient cancers ... See more keywords
Abstract 3104: A NanoBRET target engagement assay for querying domain selectivity at full-length polymerase theta in live cells
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DOI: 10.1158/1538-7445.am2024-3104
Abstract: In HR-deficient cells, Polymerase Theta (Pol-theta) serves to repair double strand breaks and has emerged as a therapeutic target in HR-deficient cancers. Encoded by the POLQ gene, Pol-theta is a large (290 Kda) protein with… read more here.
Keywords: live cells; polymerase theta; target; domain ... See more keywords
DNA polymerase theta protects leukemia cells from metabolic-induced DNA damage.
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DOI: 10.1182/blood.2022018428
Abstract: Leukemia cells accumulate DNA damage but altered DNA repair mechanisms protect them from apoptosis. We showed here that formaldehyde generated by serine/one-carbon cycle metabolism contributed to accumulation of toxic DNA-protein crosslinks (DPCs) in leukemia cells,… read more here.
Keywords: leukemia cells; dna; dna polymerase; dna damage ... See more keywords
A phase 1/2 dose escalation study of the oral DNA polymerase theta inhibitor (POLQi) GSK4524101 ± niraparib in adults with advanced or metastatic solid tumors.
Sign Up to like & getrecommendations! Published in 2025 at "Journal of Clinical Oncology"
DOI: 10.1200/jco.2025.43.16_suppl.tps3174
Abstract: TPS3174 Background: In homologous recombination-deficient (HRd) tumors, use of a PARP inhibitor (PARPi) leads to generation of DNA breaks that cannot be effectively repaired, thus selectively killing cancer cells via synthetic lethality. An alternative DNA… read more here.
Keywords: oncology; dna polymerase; solid tumors; polymerase theta ... See more keywords