ArticleOncotarget2017
Novel PARP1/2 inhibitor mefuparib hydrochloride elicits potent in vitro and in vivo anticancer activity, characteristic of high tissue distribution.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 41 citations in OpenAlex.
- Role of Poly (ADP-Ribose) Polymerase-1 (PARP1) and Its Inhibitors for Cancer Therapy.Mini reviews in medicinal chemistry · 2026Review
- Phase I Clinical Trial of CVL218, a Novel PARP1/2 Inhibitor, in Patients with Advanced Solid Tumors.MedComm · 2025Article
- Article
- Thioparib inhibits homologous recombination repair, activates the type I IFN response, and overcomes olaparib resistance.EMBO molecular medicine · 2023Article
- Targeting DNA repair for cancer treatment: Lessons from PARP inhibitor trials.Oncology research · 2023Review
- Repeated treatments of Capan-1 cells with PARP1 and Chk1 inhibitors promote drug resistance, migration and invasion.Cancer biology & therapy · 2022Article
- Absorption, distribution, metabolism, and excretion of [Cancer chemotherapy and pharmacology · 2022Article
- Discovery of MTR-106 as a highly potent G-quadruplex stabilizer for treating BRCA-deficient cancers.Investigational new drugs · 2021Article
- Combination treatment with cisplatin, paclitaxel and olaparib has synergistic and dose reduction potential in ovarian cancer cells.Experimental and therapeutic medicine · 2021Article
- An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19.Signal transduction and targeted therapy · 2021Article
- Immunotherapy of COVID-19 with poly (ADP-ribose) polymerase inhibitors: starting with nicotinamide.Bioscience reports · 2020Review
- Polymerase independent repression of FoxO1 transcription by sequence-specific PARP1 binding to FoxO1 promoter.Cell death & disease · 2020Article
- Novel mutations inAmerican journal of cancer research · 2020Article
- Inhibition of the BET family reduces its new target gene IDO1 expression and the production of L-kynurenine.Cell death & disease · 2019Article
- Acquired resistance of phosphatase and tensin homolog-deficient cells to poly(ADP-ribose) polymerase inhibitor and Ara-C mediated by 53BP1 loss and SAMHD1 overexpression.Cancer science · 2018Article
- Discovery of potent 2,4-difluoro-linker poly(ADP-ribose) polymerase 1 inhibitors with enhanced water solubility and in vivo anticancer efficacy.Acta pharmacologica Sinica · 2017Article
- Combining 53BP1 with BRCA1 as a biomarker to predict the sensitivity of poly(ADP-ribose) polymerase (PARP) inhibitors.Acta pharmacologica Sinica · 2017Article
Corrections and comments
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Authors and funding
24 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The approval of poly(ADP-ribose) polymerase (PARP) inhibitor AZD2281 in 2014 marked the successful establishment of the therapeutic strategy targeting homologous recombination repair defects of cancers in the clinic. However, AZD2281 has poor water solubility, low tissue distribution and relatively weak in vivo anticancer activity, which appears to become limiting factors for its clinical use. In this study, we found that mefuparib hydrochloride (MPH) was a potent PARP inhibitor, possessing prominent in vitro and in vivo anticancer activity. Notably, MPH displayed high water solubility (> 35 mg/ml) and potent PARP1/2 inhibition in a substrate-competitive manner. It reduced poly(ADP-ribose) (PAR) formation, enhanced γH2AX levels, induced G2/M arrest and subsequent apoptosis in homologous recombination repair (HR)-deficient cells. Proof-of-concept studies confirmed the MPH-caused synthetic lethality. MPH showed potent in vitro and in vivo proliferation and growth inhibition against HR-deficient cancer cells and synergistic sensitization of HR-proficient xenografts to the anticancer drug temozolomide. A good relationship between the anticancer activity and the PARP inhibition of MPH suggested that PAR formation and γH2AX accumulation could serve as its pharmacodynamic biomarkers. Its high bioavailability (40%~100%) and high tissue distribution in both monkeys and rats were its most important pharmacokinetic features. Its average concentrations were 33-fold higher in the tissues than in the plasma in rats. Our work supports the further clinical development of MPH as a novel PARP1/2 inhibitor for cancer therapy.
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Registered trials
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