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    DRUG CLASS:

    ClpP agonist

    Related drugs:
    7d
    Triple-Synergistic Therapy with Cobalt-Pheophytin Coordination Micelles for Overcoming Drug Resistance in Pancreatic Cancers. (PubMed, ACS Appl Bio Mater)
    To overcome this issue, herein, we developed a cobalt-pheophytin (CoPheo) coordination micelle chelating two chemotherapeutic agents including ONC201 and Palbociclib (Pal), yielding CoPheo-ONC201-Pal-F127. In addition, ONC201-mediated mitogen-activated protein kinase kinase (MEK) inhibition, combined with Pal-induced CDK4/6 blockade, promotes cellular senescence and remodels the tumor microenvironment. These three independent mechanisms collectively establish a mutually enhanced therapeutic strategy capable of overcoming the complex drug resistance driven by multiple downstream signaling pathways in KRAS-mutant pancreatic cancer.
    Journal
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    KRAS (KRAS proto-oncogene GTPase) • CDK4 (Cyclin-dependent kinase 4)
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    KRAS mutation
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    Ibrance (palbociclib) • Modeyso (dordaviprone)
    13d
    ONC206 demonstrates potent anti-tumorigenic activity and is a potential novel therapeutic strategy for high-risk medulloblastoma. (PubMed, Neuro Oncol)
    Our results highlight ONC206 as a novel therapeutic option for patients with high-risk medulloblastoma and provide strong rationale for testing the efficacy of ONC206 in the treatment of these patients.
    Journal
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    CLPP (Caseinolytic Mitochondrial Matrix Peptidase Proteolytic Subunit)
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    Modeyso (dordaviprone) • JZP3507
    26d
    Study of ONC206 (JZP3507) in Advanced Pheochromocytoma and Paraganglioma (clinicaltrials.gov)
    P2, N=90, Recruiting, Jazz Pharmaceuticals | Not yet recruiting --> Recruiting
    Enrollment open
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    JZP3507
    1m
    PNOC023: Open Label Phase 1 and Target Validation Study of ONC206 in Children and Young Adults with Newly Diagnosed or Recurrent Diffuse Midline Glioma (DMG), and Other Recurrent Primary Malignant Central Nervous System (CNS) Tumors. (2025-521180-13-00)
    P1, N=20, Not yet recruiting, Prinses Maxima Centrum voor Kinderoncologie B.V.
    New P1 trial
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    JZP3507
    2ms
    Preclinical efficacy of combinatorial B7-H3 CAR T cells and ONC206 against diffuse intrinsic pontine glioma. (PubMed, Neuro Oncol)
    B7-H3 CAR T cells combined with ONC206 is a feasible and efficacious multi-agent approach against multiple DIPG models.
    Preclinical • Journal
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    CD276 (CD276 Molecule) • IL2 (Interleukin 2) • GZMB (Granzyme B) • IFNL1 (Interferon Lambda 1)
    |
    JZP3507
    2ms
    A Study of ONC201 for Refractory Meningioma (clinicaltrials.gov)
    P2, N=0, Withdrawn, University of Nebraska | N=27 --> 0 | Suspended --> Withdrawn | Trial primary completion date: Apr 2026 --> Apr 2027
    Enrollment change • Trial withdrawal • Trial primary completion date
    |
    Modeyso (dordaviprone)
    2ms
    ONC201 and Atezolizumab in Obesity-Driven Endometrial Cancer (clinicaltrials.gov)
    P1, N=58, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial completion date: Jul 2026 --> Jul 2028 | Trial primary completion date: Feb 2026 --> Feb 2028
    Trial completion date • Trial primary completion date
    |
    Tecentriq (atezolizumab) • Modeyso (dordaviprone)
    2ms
    Dordaviprone/ONC201 Activation of the ClpP Mitochondrial Protease Inhibits the Growth of KRAS-Mutant Pancreatic Cancer and Overcomes RAS Inhibitor Resistance. (PubMed, bioRxiv)
    We propose that concurrent treatment with ONC201 may delay onset of resistance to RAS inhibitor therapy. ClpP activation by dordaviprone/ONC201 suppressed PDAC cell growth and overcame resistance to the RAS(ON) multi-selective inhibitor RMC-7977, providing support for investigating this combination as a potential combination treatment for KRAS-mutant pancreatic cancer.
    Journal
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    KRAS (KRAS proto-oncogene GTPase) • KEAP1 (Kelch Like ECH Associated Protein 1)
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    KRAS mutation
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    Modeyso (dordaviprone) • RMC-7977
    2ms
    Testing for Safety and Colorectal Cancer Preventive Effects of ONC201 (clinicaltrials.gov)
    P1, N=36, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Mar 2026 --> May 2027
    Trial primary completion date
    |
    BCL2 (B-cell CLL/lymphoma 2)
    |
    Modeyso (dordaviprone)
    3ms
    IRF2BPL transcriptionally regulates IGFBP2 to promote tumor progression and suppresses immune cell infiltration in esophageal squamous cell carcinoma. (PubMed, Oncogene)
    Moreover, the chemical drug ONC201 was shown to effectively impede ESCC progression induced by the hyperactive IRF2BPL-IGFBP2 axis in tumor cells. Collectively, our findings verified that the IRF2BPL-IGFBP2 axis plays a critical role in enhancing ESCC progression by increasing the malignancy of ESCC cells and fostering an immune-deficient tumor microenvironment. Targeting the IRF2BPL-IGFBP2 axis may represent a promising therapeutic strategy for ESCC.
    Journal
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    IGFBP2 (Insulin-like growth factor binding protein 2)
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    Modeyso (dordaviprone)
    3ms
    ONC206-001: Phase I Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms (clinicaltrials.gov)
    P1, N=102, Recruiting, Jazz Pharmaceuticals | Trial primary completion date: Dec 2025 --> Jul 2026
    Trial primary completion date • First-in-human
    |
    JZP3507
    3ms
    Study of ONC206 (JZP3507) in Advanced Pheochromocytoma and Paraganglioma (clinicaltrials.gov)
    P2, N=90, Not yet recruiting, Jazz Pharmaceuticals
    New P2 trial
    |
    JZP3507