RTx-303, an Orally Bioavailable Polθ Polymerase Inhibitor That Potentiates PARP Inhibitors in BRCA Mutant Tumors.

doi:10.1021/acs.jmedchem.5c00551

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RTx-303, an Orally Bioavailable Polθ Polymerase Inhibitor That Potentiates PARP Inhibitors in BRCA Mutant Tumors.

Journal of medicinal chemistry - 13 Nov 2025

Chandramouly Gurushankar, Fried William, Gordon John, Ralph Douglas, Keuk Channita, Kumari Sangeeta, Ramanjulu Mercy, Auerbacher William, Minakhin Leonid, Tredinnick Taylor, Tiberi Bernadette, Morton George, Betsch Robert, Cai Kathy Q, Vekariya Umeshkumar M, Tyagi Mrityunjay, Skorski Tomasz, Karakashev Sergey, Johnson Neil, Childers Wayne E, Chen Xiaojiang S, Pomerantz Richard T

Abstract excerpt

DNA polymerase θ (Polθ) is a polymerase-helicase fusion protein that is synthetically lethal with homologous recombination (HR) factors, such as BRCA1/2, and confers resistance to PARP inhibitors (PARPi) and other genotoxic cancer therapies. Previously developed Polθ polymerase (Polθ-pol) inhibitors (Polθi) exhibited limited pharmacological activity and metabolic stability, warranting the development of a Polθi...

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PMID: 41124685
DOI: 10.1021/acs.jmedchem.5c00551
PMCID: PMC12621202

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BRCA1

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RTx-303, an Orally Bioavailable Polθ Polymerase Inhibitor That Potentiates PARP Inhibitors in BRCA Mutant Tumors.PMID 41124685Read ↗

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