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    2ms
    Trial to Evaluate Safety and Tolerability of GP-2250 in Combination With Gemcitabine (clinicaltrials.gov)
    P1, N=64, Recruiting, Geistlich Pharma AG | Trial completion date: Aug 2024 --> Dec 2024 | Trial primary completion date: Mar 2024 --> Sep 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    gemcitabine • 5-fluorouracil • misetionamide (GP-2250)
    6ms
    Antineoplastic activity of GP-2250 in-vitro and in mouse xenograft models. (PubMed, Anticancer Drugs)
    GP-2250 demonstrated cytotoxic activity in vitro and reduced the tumor volume in a variety of human cancer cell lines in a xenograft mouse model. Given these results, as well as evidence of synergism with other anticancer drugs, GP-2250 shows promise as a new therapeutic agent for treating human cancers and is being evaluated in a phase 1 dose-escalation study (NCT03854100).
    Journal • Preclinical
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    OncoPanel™ Assay
    |
    misetionamide (GP-2250)
    6ms
    In Vitro Experiments on the Effects of GP-2250 on BRAF-Mutated Melanoma Cell Lines and Benign Melanocytes. (PubMed, Int J Mol Sci)
    GP-2250 is able to downregulate the gene and protein expression of aberrant tumorigenic pathways in melanoma cell lines. Since GP-2250 is a GAPDH inhibitor, the substance may be a promising combination therapy for tumors presenting the Warburg effect, such as melanoma.
    Preclinical • Journal
    |
    BRAF (B-raf proto-oncogene) • STAT3 (Signal Transducer And Activator Of Transcription 3) • GAPDH (Glyceraldehyde-3-Phosphate Dehydrogenase) • ANXA5 (Annexin A5)
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    BRAF mutation • STAT3 expression
    |
    misetionamide (GP-2250)
    9ms
    The effect of GP-2250 on cultured virus-negative Merkel cell carcinoma cells: preliminary results. (PubMed, J Cancer Res Clin Oncol)
    The present study indicates GP-2250 having anti-neoplastic effects in MCPyV-negative tumor cells in regard to viability, proliferation, and migration. Moreover, the substance is capable of downregulating protein expression of aberrant tumorigenic pathways in MCPyV-negative MCC cells.
    Journal • Tumor mutational burden • IO biomarker
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    TMB (Tumor Mutational Burden) • NOTCH1 (Notch 1) • STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    NOTCH1 expression • STAT3 expression
    |
    misetionamide (GP-2250)
    9ms
    Oxathiazinane derivatives display both antineoplastic and antibacterial activity: a structure activity study. (PubMed, J Cancer Res Clin Oncol)
    Thus, a comparable structure activity relationship became apparent for both the antineoplastic and antibacterial activity.
    Journal
    |
    misetionamide (GP-2250)
    10ms
    GP-2250, a novel anticancer agent, inhibits the energy metabolism, activates AMP-Kinase and impairs the NF-kB pathway in pancreatic cancer cells. (PubMed, J Cell Mol Med)
    The upregulation of p53 concomitant with an excess of ROS supported apoptosis. Thus, the anticancer activity of GP-2250 is a result of disruption of energy metabolism and inhibition of tumour promotion by NF-κB.
    Journal
    |
    BCL2 (B-cell CLL/lymphoma 2) • CCND1 (Cyclin D1) • GAPDH (Glyceraldehyde-3-Phosphate Dehydrogenase)
    |
    misetionamide (GP-2250)
    1year
    Mechanisms and rational combinations with gp-2250, a novel oxathiazine derivative, in ovarian cancer (AACR 2023)
    In vivo experiments were carried out to determine the therapeutic efficacy of GP-2250 alone and in combination with standard-of-care drugs (e.g., paclitaxel, cisplatin topotecan, and poly ADP-ribose polymerases (PARP) inhibitors. We investigated the cytotoxic effect of GP-2250 in 10 ovarian cancer cell lines and found that HRD ovarian cancer cells (e.g., Kuramochi, OVCAR4, and OVCAR8) were more vulnerable to GP-2250 than HRP ovarian cancer cells (e.g., A2780 and OVCAR5). Taken together, our data indicate that GP-2250 exerts profound effects on tumor metabolism and combination with PARP inhibitors or bevacizumab showed promising anti-tumor efficacy. These findings could have implications for the clinical development of GP-2250.
    PARP Biomarker
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    HIF1A (Hypoxia inducible factor 1, alpha subunit) • HK2 (Hexokinase 2) • ANXA5 (Annexin A5)
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    Avastin (bevacizumab) • Lynparza (olaparib) • cisplatin • paclitaxel • Zejula (niraparib) • Rubraca (rucaparib) • topotecan • misetionamide (GP-2250)
    over3years
    Trial to Evaluate Safety and Tolerability of GP-2250 in Combination With Gemcitabine (clinicaltrials.gov)
    Trial completion date: Feb 2021 --> Dec 2021 | Trial primary completion date: Dec 2020 --> Dec 2021
    Clinical • Trial completion date • Trial primary completion date • Combination therapy
    |
    ALB (Albumin)
    |
    gemcitabine • misetionamide (GP-2250)