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    DRUG CLASS:

    PTPN2 inhibitor

    Related drugs:
    Associations

    News

    Trials
    1m
    Targeting Protein Tyrosine Phosphatase Nonreceptor Type 2 with a Novel Inhibitor for the Treatment of Melanoma. (PubMed, J Med Chem)
    It enhanced lymphocyte infiltration into tumors and modulated IFN-γ signaling pathways. These findings indicate that compound K-38 is a potent small molecule inhibitor of PTPN2, laying the groundwork for the future development of PTPN2-targeted therapeutics.
    Journal
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    IFNG (Interferon, gamma) • PTPN2 (Protein Tyrosine Phosphatase Non-Receptor Type 2)
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    osunprotafib (ABBV-CLS-484)
    2ms
    Development of Novel PTPN2/1 Inhibitors for the Treatment of Melanoma. (PubMed, J Med Chem)
    In B16-OVA syngeneic models, WS35 monotherapy and its combination with an anti-PD-1 antibody achieved robust tumor growth suppression, outperforming AC484, with no observable systemic toxicity. Collectively, WS35 represents a preclinical candidate with validated efficacy and safety for developing novel antimelanoma therapeutics.
    Journal
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    CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • PTPN1 (Protein Tyrosine Phosphatase Non-Receptor Type 1) • PTPN2 (Protein Tyrosine Phosphatase Non-Receptor Type 2)
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    osunprotafib (ABBV-CLS-484)
    3ms
    First In Human Study With ABBV-CLS-579 When Given Alone and In Combination In Participants With Locally Advanced Or Metastatic Tumors (clinicaltrials.gov)
    P1, N=101, Completed, AbbVie | Active, not recruiting --> Completed
    Trial completion • First-in-human
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    PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
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    PD-L1 expression • MSI-H/dMMR
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    PD-L1 IHC 22C3 pharmDx
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    ABBV-CLS-579
    4ms
    First In Human Study With ABBV-CLS-579 When Given Alone and In Combination In Participants With Locally Advanced Or Metastatic Tumors (clinicaltrials.gov)
    P1, N=101, Active, not recruiting, AbbVie | Trial completion date: May 2026 --> Aug 2025 | Trial primary completion date: May 2026 --> Aug 2025
    Trial completion date • Trial primary completion date
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    PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
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    PD-L1 expression • MSI-H/dMMR
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    PD-L1 IHC 22C3 pharmDx
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    ABBV-CLS-579
    5ms
    PTPN2 Inhibition Disrupts Mitochondrial Renewal and Blocks TFRC-Mediated Mitophagy to Exert Anti-Tumor Activities in ALK-Positive Anaplastic Large Cell Lymphoma. (PubMed, Adv Sci (Weinh))
    Interestingly, TFRC is directly regulated by the transcription factor hypoxia-inducible factor 1 alpha (HIF1A) in its promoter. Notably, an orally bioavailable potent PTPN2/N1 active-site inhibitor ABBV-CLS-484 (AC484) demonstrates significant therapeutic potential against ALK+ ALCL by disturbing mitochondrial renewal and blocking TFRC-mediated PINK1-PRKN-dependent mitophagy to exert anti-tumor activities, providing critical insights into the selection of targeted treatment strategies for ALK+ ALCL patients and a strong rationale for advancing AC484 into clinical trials.
    Journal
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    ALK (Anaplastic lymphoma kinase) • PTEN (Phosphatase and tensin homolog) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • PTPN2 (Protein Tyrosine Phosphatase Non-Receptor Type 2) • UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5)
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    ALK positive
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    osunprotafib (ABBV-CLS-484)
    10ms
    Study With ABBV-CLS-484 in Participants With Locally Advanced or Metastatic Tumors (clinicaltrials.gov)
    P1, N=248, Recruiting, AbbVie | Trial primary completion date: Aug 2025 --> Oct 2026
    Trial primary completion date
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    PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
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    MSI-H/dMMR
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    osunprotafib (ABBV-CLS-484)
    10ms
    A Medicinal Chemistry Perspective on Protein Tyrosine Phosphatase Nonreceptor Type 2 in Tumor Immunology. (PubMed, J Med Chem)
    This review outlines the structural modification processes of PTPN2-targeted agents, focusing primarily on inhibitors and degraders. Finally, this review endeavors to provide a comprehensive perspective on the evolving field of PTPN2-targeted drug discovery for tumor immunotherapy, offering valuable insights for future drug development.
    Review • Journal
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    IFNG (Interferon, gamma) • IL2 (Interleukin 2) • PTPN1 (Protein Tyrosine Phosphatase Non-Receptor Type 1) • PTPN2 (Protein Tyrosine Phosphatase Non-Receptor Type 2)
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    osunprotafib (ABBV-CLS-484)
    1year
    Structure-activity relationship studies and design of a PTPN22 inhibitor with enhanced isozyme selectivity and cellular efficacy. (PubMed, Eur J Med Chem)
    Notably, our efforts yielded compound 8b-19, an essentially equipotent scaffold with superior isozyme selectivity, improved aqueous solubility, and significantly enhanced cellular efficacy compared to the parent 8b. This compound may serve as a lead for further optimization of PTPN22-targeting immunotherapies or as a chemical probe for interrogation for additional links between PTPN22 and immunomodulation in cells.
    Journal
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    PTPN2 (Protein Tyrosine Phosphatase Non-Receptor Type 2) • PTPN22 (Protein Tyrosine Phosphatase Non-Receptor Type 22)
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    PTPN2 mutation
    1year
    First In Human Study With ABBV-CLS-579 When Given Alone and In Combination In Participants With Locally Advanced Or Metastatic Tumors (clinicaltrials.gov)
    P1; Recruiting --> Active, not recruiting | N=263 --> 101 | Trial primary completion date: Aug 2025 --> May 2026
    Trial primary completion date • Enrollment change • Enrollment closed
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    PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
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    PD-L1 expression • MSI-H/dMMR
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    PD-L1 IHC 22C3 pharmDx
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    ABBV-CLS-579
    over1year
    The HIV latency reversing agent HODHBt inhibits the phosphatases PTPN1 and PTPN2. (PubMed, JCI Insight)
    The small molecule ABBV-CLS-484 (AC-484) is an active site inhibitor of PTPN1 and PTPN2 currently in clinical trials for advanced solid tumors. We compared AC-484 and HODHBt and found similar effects on STAT5 and immune activation albeit with different mechanisms of action leading to varying effects on latency reversal. Our studies provide the first specific evidence that enhancing STAT phosphorylation via inhibition of PTPN1 and PTPN2 is an effective tool against HIV.
    Journal
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    CD8 (cluster of differentiation 8) • PTPN1 (Protein Tyrosine Phosphatase Non-Receptor Type 1) • PTPN2 (Protein Tyrosine Phosphatase Non-Receptor Type 2)
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    osunprotafib (ABBV-CLS-484)
    almost2years
    Expanded Access to ABBV-CLS-484 (clinicaltrials.gov)
    P=N/A, N=0, Available, Calico Life Sciences LLC
    New trial
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    osunprotafib (ABBV-CLS-484)
    2years
    A Phase 1 Study With ABBV-CLS-484 in Subjects With Locally Advanced or Metastatic Tumors (clinicaltrials.gov)
    P1, N=248, Recruiting, Calico Life Sciences LLC | Trial completion date: Feb 2024 --> Oct 2026 | Trial primary completion date: Oct 2023 --> Aug 2025
    Trial completion date • Trial primary completion date • Metastases
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    PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
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    MSI-H/dMMR
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    osunprotafib (ABBV-CLS-484)