^
    3d
    JPI-547, a novel dual inhibitor of PARP1/2 and tankyrase is more effective than first-generation PARP inhibitors in preclinical BRCA1/2-mutated cancer models. (PubMed, Br J Cancer)
    These results suggest the scientific rationale for further clinical development of JPI-547 for treating both PARP inhibitor-sensitive patients and those resistant to first-generation PARP inhibitors in BRCA-mutated cancers.
    Preclinical • Journal • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A)
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    BRCA2 mutation • BRCA1 mutation • BRCA mutation
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    Lynparza (olaparib) • nesuparib (JPI-547)
    3d
    Food and Ethnicity Effects on Pharmacokinetics and Safety of JPI-547 in Healthy Male Participants (clinicaltrials.gov)
    P1, N=36, Not yet recruiting, Onconic Therapeutics Inc.
    New P1 trial
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    nesuparib (JPI-547)
    10d
    A new hope: Clinical advances in targeted therapies for pediatric diffuse midline glioma. (PubMed, Neurooncol Adv)
    Among these are histone deacetylase inhibitors (HDACis), receptor tyrosine kinase inhibitors, and novel agents such as ONC201 and unesbulin that target metabolic and epigenetic pathways respectively...Despite these advances, challenges such as drug delivery across the blood-brain barrier and therapeutic resistance persist, necessitating the development of combination therapies and innovative delivery methods. Ongoing research is focused on refining these strategies and exploring additional molecular and immunological targets to improve outcomes for children with DMG.
    Review • Journal
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    CD276 (CD276 Molecule)
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    nesuparib (JPI-547) • Modeyso (dordaviprone) • unesbulin (BMIi-1)
    26d
    Study to Assess the Safety, Tolerability of JPI-547 in Combination With Modified FOLFIRINOX or Gemcitabine-nab-paclitaxel in Patients With Locally Advanced and Metastatic Pancreatic Cancer (clinicaltrials.gov)
    P1/2, N=71, Recruiting, Onconic Therapeutics Inc. | Phase classification: P1 --> P1/2 | N=30 --> 71 | Trial completion date: Jun 2026 --> Apr 2030 | Trial primary completion date: Mar 2026 --> Apr 2030
    Phase classification • Enrollment change • Trial completion date • Trial primary completion date
    |
    gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • oxaliplatin • irinotecan • leucovorin calcium • nesuparib (JPI-547)
    1m
    UPR/ATF4/Noxa pathway overactivation through SERCA2 inhibition or ONC201 treatment combined with ABT-737 triggers apoptosis in chemoresistant ovarian cancer cells and patient-derived tumor organoids. (PubMed, Cell Death Dis)
    Ovarian cancer has a poor clinical prognosis due to chemoresistance following carboplatin/paclitaxel treatment...The therapeutic efficacy of these combinations was also proved in patient-derived tumor organoid models (PDTO), leading to their structural disintegration and reduced viability. Collectively, our study highlights that ABT-737, through BCL-xL inhibition and synergy with ER stress inducers, triggers ovarian cancer death, offering promising strategies for overcoming chemoresistance in relapsed ovarian cancer.
    Journal • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • ATF4 (Activating Transcription Factor 4)
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    carboplatin • paclitaxel • nesuparib (JPI-547) • Modeyso (dordaviprone) • ABT-737
    3ms
    To Evaluate the Efficacy and Safety of JPI-547 in Combination With Bevacizumab as Maintenance Therapy in Relapsed Ovarian Cancer (clinicaltrials.gov)
    P2, N=81, Not yet recruiting, Onconic Therapeutics Inc.
    New P2 trial
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
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    HRD • BRCA mutation
    |
    Avastin (bevacizumab) • nesuparib (JPI-547)
    4ms
    To Evaluate the Safety and Tolerability of Study Drug as a Third-line and Beyond Therapy for Recurrent or Metastatic Gastric Cancer (clinicaltrials.gov)
    P1/2, N=49, Not yet recruiting, Onconic Therapeutics Inc.
    New P1/2 trial
    |
    irinotecan • nesuparib (JPI-547)
    5ms
    Small Molecule Activators of the Mitochondrial Protease ClpP Induce Senescence in Triple-Negative Breast Cancer Cells and Sensitize Cells to the Bcl-2 Inhibitor Venetoclax. (PubMed, Res Sq)
    We report that ONC201 and highly potent second generation ClpP agonists (TR-57, TR-107), promote induction of senescence in triple-negative breast cancer (TNBC) cell lines...By contrast, cells treated with the cell cycle inhibitor and senescence inducer, abemaciclib rapidly regained p-Rb and Myc expression and cell proliferation following washout...Combining a ClpP agonist with a PARP inhibitor (olaparib) produced an additive effect. In summary, we show that ClpP activators stably induce an irreversible senescence in a ClpP-dependent manner that synergizes with venetoclax in TNBC cells.
    Journal • PARP Biomarker • IO biomarker
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    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CHEK2 (Checkpoint kinase 2) • TP53BP1 (Tumor Protein P53 Binding Protein 1)
    |
    Venclexta (venetoclax) • Lynparza (olaparib) • Verzenio (abemaciclib) • nesuparib (JPI-547) • Modeyso (dordaviprone)
    8ms
    JPI-547, a Dual Inhibitor of PARP/Tankyrase, Shows Antitumor Activity Against Pancreatic Cancers with Homologous Recombination Repair Deficiency or Wnt-Addiction. (PubMed, Int J Biol Sci)
    JPI-547 outperformed most PARP inhibitors, with a half-maximal inhibitory concentration approximately 10-fold lower than that of olaparib. PDAC cells reliant on Wnt signaling due to pathogenic RNF43 mutations showed increased susceptibility to JPI-547 without altering homologous recombination repair efficiency. JPI-547 disrupts the Wnt/β-catenin pathway in RNF43-mutated cells and inhibits the oncogenic YAP pathway, highlighting its multifaceted therapeutic potential in PDAC with HRD or Wnt-addiction.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • RNF43 (Ring Finger Protein 43)
    |
    HRD
    |
    Lynparza (olaparib) • nesuparib (JPI-547)
    10ms
    The therapeutic potential of repurposed mebendazole, alone and in synergistic combination with ONC201, in the treatment of diffuse midline glioma. (PubMed, Am J Cancer Res)
    Finally, one pair of ONC201-sensitive and ONC201-resistant DMG cell lines with acquired resistance showed same responsiveness to MBZ with similar values of IC50 and Emax. In conclusion, MBZ demonstrates high growth-inhibitory/proapoptotic activity, chemosensitization property to ONC201 and the ability to overcome ONC201 resistance in DMG cell cultures, proposing as a new low-toxicity therapeutic for DMG, with a potential to be used in second-line treatment and/or in combination protocols.
    Journal • PARP Biomarker
    |
    CASP3 (Caspase 3) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • ANXA5 (Annexin A5)
    |
    nesuparib (JPI-547) • Modeyso (dordaviprone) • mebendazole
    1year
    PENELOPE: First-line Carboplatin and Paclitaxel in Combination With Pembrolizumab, Followed by Maintenance Pembrolizumab With or Without Nesuparib, in Patients With Newly Diagnosed Advanced or Recurrent MMR-proficient (pMMR) Endometrial Cancer (clinicaltrials.gov)
    P2, N=92, Recruiting, Yonsei University | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Keytruda (pembrolizumab) • carboplatin • paclitaxel • nesuparib (JPI-547)
    1year
    Study to Assess the Safety, Tolerability of JPI-547 in Combination With Modified FOLFIRINOX or Gemcitabine-nab-paclitaxel in Patients With Locally Advanced and Metastatic Pancreatic Cancer (clinicaltrials.gov)
    P1, N=30, Recruiting, Onconic Therapeutics Inc. | Trial completion date: Sep 2026 --> Jun 2026
    Trial completion date
    |
    gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • oxaliplatin • irinotecan • leucovorin calcium • nesuparib (JPI-547)