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

    IRS2 inhibitor

    Related drugs:
    Associations

    News

    Trials
    6ms
    NT219 Combined With Standard of Care Biologic Therapy in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov)
    P1/2, N=29, Recruiting, University of Colorado, Denver | Not yet recruiting --> Recruiting
    Enrollment open
    |
    PD-L1 (Programmed death ligand 1)
    |
    Keytruda (pembrolizumab) • Erbitux (cetuximab) • NT219
    8ms
    NT219 Combined With Standard of Care Biologic Therapy in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov)
    P1/2, N=29, Not yet recruiting, University of Colorado, Denver
    New P1/2 trial
    |
    PD-L1 (Programmed death ligand 1)
    |
    Keytruda (pembrolizumab) • Erbitux (cetuximab) • NT219
    11ms
    IRS2 as a driver of brain metastasis in colorectal cancer: a potential target for novel therapeutic strategies. (PubMed, Neuro Oncol)
    Our work underscores the unique role of IRS2 in facilitating CRC brain adaptation and suggests a novel therapeutic strategy for CRC patients with BM.
    Journal
    |
    CTNNB1 (Catenin (cadherin-associated protein), beta 1) • IRS2 (Insulin receptor substrate 2)
    |
    5-fluorouracil • NT219
    1year
    ASPSCR1::TFE3-mediated upregulation of insulin receptor substrate 2 (IRS-2) activates PI3K/AKT signaling and promotes malignant phenotype. (PubMed, Int J Biochem Cell Biol)
    Pharmacological inhibition of IRS-2 also reduced AKT activation as well as cell viability, migration, invasion, and adhesion. These findings suggest that IRS-2, regulated by ASPSCR1::TFE3, promotes tumor progression by activating PI3K/AKT signaling and enhancing the malignant phenotype.
    Journal
    |
    TFE3 (Transcription Factor Binding To IGHM Enhancer 3) • IRS2 (Insulin receptor substrate 2) • ASPSCR1 (ASPSCR1 Tether For SLC2A4)
    |
    TFE3 fusion
    1year
    A Study to Evaluate NT219 Alone and in Combination with ERBITUX® (Cetuximab) in Adults with Advanced Solid Tumors and Head and Neck Cancer (clinicaltrials.gov)
    P1/2, N=52, Completed, TyrNovo Ltd. | Active, not recruiting --> Completed | N=110 --> 52
    Trial completion • Enrollment change • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
    |
    KRAS wild-type • RAS wild-type • RAS wild-type + BRAF wild-type
    |
    Erbitux (cetuximab) • NT219
    over1year
    A Study to Evaluate NT219 Alone and in Combination With ERBITUX® (Cetuximab) in Adults With Advanced Solid Tumors and Head and Neck Cancer (clinicaltrials.gov)
    P1/2, N=110, Active, not recruiting, TyrNovo Ltd. | Trial completion date: Sep 2024 --> Jun 2024
    Trial completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
    |
    KRAS wild-type • RAS wild-type • RAS wild-type + BRAF wild-type
    |
    Erbitux (cetuximab) • NT219
    almost2years
    A Study to Evaluate NT219 Alone and in Combination With ERBITUX® (Cetuximab) in Adults With Advanced Solid Tumors and Head and Neck Cancer (clinicaltrials.gov)
    P1/2, N=110, Active, not recruiting, TyrNovo Ltd. | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
    |
    KRAS wild-type • RAS wild-type • RAS wild-type + BRAF wild-type
    |
    Erbitux (cetuximab) • NT219
    almost2years
    A Study to Evaluate NT219 Alone and in Combination With ERBITUX® (Cetuximab) in Adults With Advanced Solid Tumors and Head and Neck Cancer (clinicaltrials.gov)
    P1/2, N=110, Recruiting, TyrNovo Ltd.
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
    |
    KRAS wild-type • RAS wild-type • RAS wild-type + BRAF wild-type
    |
    Erbitux (cetuximab) • NT219
    2years
    A Study to Evaluate NT219 Alone and in Combination With ERBITUX® (Cetuximab) in Adults With Advanced Solid Tumors and Head and Neck Cancer (clinicaltrials.gov)
    P1/2, N=110, Recruiting, TyrNovo Ltd. | N=75 --> 110 | Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: Jun 2023 --> Jun 2024
    Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
    |
    KRAS wild-type • RAS wild-type • RAS wild-type + BRAF wild-type
    |
    Erbitux (cetuximab) • NT219
    over2years
    The Insulin Receptor Substrate 2 Mediates the Action of Insulin on HeLa Cell Migration via the PI3K/Akt Signaling Pathway. (PubMed, Curr Issues Mol Biol)
    While PI3K reached the highest level at 30 min after treatment (p ≤ 0.05), AKT had the highest levels from 15 min (p ≤ 0.05) and remained constant for 6 h. ERK1 and ERK2 expression was also observed, but only ERK2 was phosphorylated in a time-dependent manner, reaching a maximum peak 5 min after insulin stimulation. Although no effect on cell proliferation was observed, insulin stimulation of HeLa cells markedly promoted cell migration.
    Journal
    |
    IRS2 (Insulin receptor substrate 2) • MAPK1 (Mitogen-activated protein kinase 1)
    almost3years
    NT219 induces tumor PD-L1 expression and potentiates anti-PD-1 efficacy (AACR 2023)
    In addition, to evaluate the combination effect of NT219 with ICB therapy in ICB-resistant PDX model, we used a humanized PDX model of pembrolizumab-resistant gastroesophageal tumor (GEJ). To summarize, we found a significant synergistic effect of NT219 combined with anti-PD-1 therapy, supported by a mechanism of PDL-1 induction making ICB resistant tumors amenable to ICB treatment. Collectively, these findings demonstrated that NT219 has the potential to reverse ICB resistance in both human PDX and murine syngeneic tumor model systems
    Clinical • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression • BRAF mutation
    |
    Keytruda (pembrolizumab) • NT219
    over3years
    Mutation analysis of circulating tumor DNA and paired ascites and tumor tissues in ovarian cancer. (PubMed, Exp Ther Med)
    Taken together, the present study focused on the mutant genes in ctDNA, ascites and tumor tissues, and suggested that the integrated information of different samples could be examined to comprehensively reflect the mutational landscape in ovarian cancer. However, procedures and protocols to interpret and utilize the integrated information obtained from various forms of liquid biopsies will require optimization prior to their use for future clinical applications.
    Journal • Circulating tumor DNA
    |
    PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor) • NOTCH2 (Notch 2) • NOTCH3 (Notch Receptor 3) • IRS2 (Insulin receptor substrate 2) • YBX1 (Y-Box Binding Protein 1)