^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    DRUG:

    LB-100

    i
    Other names: LB-100, LB 100, LB-1
    Company:
    Lixte Biotech, National Institute of Health and Medical Research
    Drug class:
    PP2A inhibitor
    Related drugs:
    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
    |
    ANXA5 (Annexin A5)
    |
    Epidaza (chidamide) • LB-100
    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
    |
    CIP2A (Cellular Inhibitor Of PP2A)
    |
    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
    |
    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)
    |
    LB-100
    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
    over1year
    CoLBAt: LB-100 (PP2A Inhibitor) and Atezolizumab (PD-L1 Inhibitor) in Metastatic Colorectal Cancer Patients (clinicaltrials.gov)
    P1, N=37, Recruiting, The Netherlands Cancer Institute | Not yet recruiting --> Recruiting
    Enrollment open
    |
    CD4 (CD4 Molecule)
    |
    Tecentriq (atezolizumab) • LB-100
    over1year
    Design and Synthesis of 7-Oxabicyclo[2.2.1]heptane-2,3-dicarboxylic Acid Derivatives as PP5 Inhibitors To Reverse Temozolomide Resistance in Glioblastoma Multiforme. (PubMed, J Med Chem)
    Furthermore, oral administration of 28a and TMZ was well tolerated to effectively inhibit tumor growth (TGI = 87.7%) in the xenograft model. Collectively, these results implicate 28a could be a drug candidate by reversing TMZ resistance with a selective PP5 inhibition manner.
    Journal
    |
    CCND1 (Cyclin D1)
    |
    temozolomide • LB-100
    over1year
    Canonical and Noncanonical Functions of the BH3 Domain Protein Bid in Apoptosis, Oncogenesis, Cancer Therapeutics, and Aging. (PubMed, Cancers (Basel))
    The unexpected upregulation of this Bid protein in cancer cells can also be instrumental in explaining the mechanisms behind acquired chemoresistance. The stable protein associations at the mitochondria between tBid and anti-apoptotic mitochondrial ATR play a crucial role in maintaining the viability of cancer cells, suggesting a novel mechanism to induce cancer cell apoptosis by freeing tBid from the ATR associations at mitochondria.
    Review • Journal
    |
    BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1)
    |
    LB-100
    almost2years
    Safety and Efficacy of Targeting PP2A in Ovarian Clear Cell Carcinoma Using Dostarlimab and LB-100 (clinicaltrials.gov)
    P1/2, N=21, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026
    Trial completion date • Trial primary completion date
    |
    CD4 (CD4 Molecule)
    |
    Jemperli (dostarlimab-gxly) • LB-100
    2years
    Safety and Efficacy of Targeting PP2A in Ovarian Clear Cell Carcinoma Using Dostarlimab and LB-100 (clinicaltrials.gov)
    P1/2, N=21, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting | Initiation date: Mar 2024 --> Nov 2023
    Enrollment open • Trial initiation date
    |
    CD4 (CD4 Molecule)
    |
    Jemperli (dostarlimab-gxly) • LB-100
    2years
    LB-100 (PP2A Inhibitor) and Azenosertib (WEE1 Inhibitor) in Metastatic Colorectal Cancer Patients (clinicaltrials.gov)
    P1, N=43, Not yet recruiting, The Netherlands Cancer Institute
    New P1 trial • Metastases
    |
    azenosertib (ZN-c3) • LB-100
    2years
    Safety and Efficacy of Targeting PP2A in Ovarian Clear Cell Carcinoma Using Dostarlimab and LB-100 (clinicaltrials.gov)
    P1/2, N=21, Not yet recruiting, M.D. Anderson Cancer Center
    New P1/2 trial
    |
    CD4 (CD4 Molecule)
    |
    Jemperli (dostarlimab-gxly) • LB-100