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    DRUG CLASS:

    PP2A inhibitor

    Related drugs:
    2ms
    First-in-human Phase I to Evaluate PEP-010 as Single Agent and in Combination With Paclitaxel or With Gemcitabine (CleverPeptide) (clinicaltrials.gov)
    P1, N=101, Recruiting, Institut Curie | Trial primary completion date: Jul 2025 --> Nov 2025
    Trial primary completion date • First-in-human
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    gemcitabine • paclitaxel • PEP-010
    3ms
    Synergistic Efficacy of Chidamide and LB100 in Sézary Syndrome via TNC Downregulation and PI3K/AKT/mTOR Dephosphorylation. (PubMed, Cancer Sci)
    This study also preliminarily validated the effect of the combination of the two drugs on other subtypes of CTCL. Overall, these findings provide potential new therapeutic strategies for CTCL (especially SS), although further clinical evaluation is required to validate these results.
    Journal
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    ANXA5 (Annexin A5)
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    Epidaza (chidamide) • LB-100
    4ms
    Canagliflozin inhibits hepatic stellate cells activation and proliferation by inhibiting PP2A-mediated β-catenin dephosphorylation to attenuate hepatic fibrosis. (PubMed, Int Immunopharmacol)
    In conclusion, our study indicates that Canagliflozin ameliorate HF via inhibiting PP2A-mediated dephosphorylation of β-catenin in HSCs. The inhibition of PP2A in HSCs may represent a potential therapeutic target not only for cancer treatment but also for the management of HF.
    Journal
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    CTNNB1 (Catenin (cadherin-associated protein), beta 1)
    7ms
    A PP2A-mtATR-tBid axis links DNA damage-induced CIP2A degradation to apoptotic dormancy and therapeutic resistance in PDAC. (PubMed, Cancer Lett)
    We found that in gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) cells, CIP2A degradation via ubiquitination enhanced PP2A phosphatase activity, leading to the dephosphorylation of ATR at Ser428 in the cytoplasm...These findings reveal a novel mechanism of resistance to DNA damage-based cancer drugs and introduce a new action mechanism of LB-100, which works through mtATR-tBid complex-mediated apoptotic dormancy triggered by CIP2A degradation-mediated PP2A activation. Disrupting the mtATR-tBid complex may represent a promising strategy to restore or sensitize resistant cancer cells to apoptosis.
    Journal
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    CIP2A (Cellular Inhibitor Of PP2A)
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    gemcitabine • LB-100
    9ms
    Enhancer: Phase I/II of LB-100 Plus Doxorubicin Vs. Doxorubicin Alone in First Line of Advanced Soft Tissue Sarcomas (clinicaltrials.gov)
    P1/2, N=152, Active, not recruiting, Grupo Espanol de Investigacion en Sarcomas | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    doxorubicin hydrochloride • LB-100
    9ms
    NLRP4 unlocks an NK/macrophages-centered ecosystem to suppress non-small cell lung cancer. (PubMed, Biomark Res)
    Altogether, we delineated NLRP4's unexplored facets and discovered an NLRP4-driven anti-tumor ecosystem composed of TIGIT+TNFA+ NK and iNOS+ M1. Finally, targeting PP2A by its inhibitor successfully mimicked the anti-tumor capacity of the overexpression of NLRP4.
    Journal • IO biomarker
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    TNFA (Tumor Necrosis Factor-Alpha) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CXCR2 (Chemokine (C-X-C motif) receptor 2) • LRP4 (LDL Receptor Related Protein 4)
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    LB-100
    11ms
    Exploratory Study on the Sensitization Effect of PP2A Inhibitor (Norcantharidin) Combined with PD-1 Inhibitor in the Treatment of Solid Tumors (ChiCTR2400094682)
    P=N/A, N=46, Shanghai Tongren Hospital; Shanghai Tongren Hospital
    New trial
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    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden)
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    PD-L1 expression
    12ms
    First-in-human Phase I to Evaluate PEP-010 As Single Agent and in Combination with Paclitaxel or with Gemcitabine (CleverPeptide) (clinicaltrials.gov)
    P1, N=101, Recruiting, Institut Curie | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jul 2025
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    gemcitabine • paclitaxel • PEP-010
    1year
    Protein phosphatase 2A inhibitor modulates natural killer cell homeostasis in peripheral tissues. (PubMed, Biochem Biophys Res Commun)
    Among various target molecules of PP2A, we found that the upregulation of c-Myc pathway and its phosphorylation, along with its downstream cyclin E expression and G1/S cell cycle transition in PP2Ai-treated mice NK cells. Our results suggest that PP2Ai modulates NK cell proliferation through c-Myc and cyclin E, leading to their maturation and trafficking from the bone marrow to the peripheral tissues.
    Journal
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    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CX3CR1 (C-X3-C Motif Chemokine Receptor 1)
    1year
    LB-100, Carboplatin, Etoposide, and Atezolizumab for the Treatment of Untreated Extensive-Stage Small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=3, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting | N=21 --> 3
    Enrollment closed • Enrollment change • Combination therapy
    |
    Tecentriq (atezolizumab) • carboplatin • etoposide IV • LB-100
    1year
    Penfluridol inhibits melanoma growth and metastasis through enhancing von Hippel‒Lindau tumor suppressor-mediated cancerous inhibitor of protein phosphatase 2A (CIP2A) degradation. (PubMed, MedComm (2020))
    Additionally, von Hippel‒Lindau (VHL) is the endogenous E3 ligase for CIP2A, and PF enhances the interaction between VHL and CIP2A, promoting the ubiquitin‒proteasome degradation of CIP2A, thereby inhibiting melanoma growth and metastasis. Overall, this study not only suggests PF's potential in treating melanoma and its brain metastases but also highlights CIP2A degradation as a therapeutic strategy for melanoma.
    Journal
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • VHL (von Hippel-Lindau tumor suppressor) • CIP2A (Cellular Inhibitor Of PP2A)