^
    26d
    Integrated analyses of multi-omic data derived from paired primary lung cancer and brain metastasis reveal the metabolic vulnerability as a novel therapeutic target. (PubMed, Genome Med)
    In conclusion, our findings not only provide comprehensive and integrated perspectives of molecular underpinnings of LC-BrMs but also contribute to the development of a potential, rationale-based combinatorial therapeutic strategy with the goal of translating it into clinical trials for patients with LC-BrMs.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • LRP1B (LDL Receptor Related Protein 1B) • MUC16 (Mucin 16, Cell Surface Associated) • TTN (Titin)
    |
    gamitrinib
    7ms
    A Phase I Safety and Pharmacokinetic Study of Gamitrinib Administered Intravenously to Patients With Advanced Cancer (clinicaltrials.gov)
    P1, N=42, Suspended, Fox Chase Cancer Center | Trial completion date: Dec 2029 --> Dec 2026 | Trial primary completion date: Dec 2028 --> Jun 2026
    Trial completion date • Trial primary completion date • Metastases
    |
    gamitrinib
    1year
    The development of cancers research based on mitochondrial heat shock protein 90. (PubMed, Front Oncol)
    Among these compounds, gamitrinib, a specific mtHsp90 inhibitor, has demonstrated its safety and efficacy in several preclinical investigations and is currently undergoing evaluation in clinical trials. This review aims to provide a comprehensive overview of the present knowledge pertaining to mtHsp90, encompassing its structure and function. Moreover, our main emphasis is on the development of mtHsp90 inhibitors for various cancer therapies, to present a thorough overview of the recent pre-clinical and clinical advancements in this field.
    Review • Journal
    |
    TNFA (Tumor Necrosis Factor-Alpha)
    |
    gamitrinib
    1year
    Inhibition of TRAP1 Accelerates the DNA Damage Response, Activation of the Heat Shock Response and Metabolic Reprogramming in Colon Cancer Cells. (PubMed, Front Biosci (Landmark Ed))
    These findings provide new insights into TRAP1-driven metabolic reprogramming in response to oxidative stress.
    Journal
    |
    TNFA (Tumor Necrosis Factor-Alpha) • HSF1 (Heat Shock Transcription Factor 1) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
    |
    gamitrinib
    2years
    Metabolic targeting of NRF2 potentiates the efficacy of the TRAP1 inhibitor G-TPP through reduction of ROS detoxification in colorectal cancer. (PubMed, Cancer Lett)
    To further elucidate the mechanistic role of TRAP1 in regulating tumor cell survival, we used gamitrinib-triphenylphosphonium (G-TPP) to inhibit TRAP1 signaling pathways in colon cancer...Furthermore, treatment with both a NRF2 inhibitor and a TRAP1 inhibitor led to excessive ROS production and exacerbated G-TPP-induced cell death in G-TPP-resistant cells. Taken together, dual targeting of TRAP1 and NRF2 may potentially overcome colon cancer resistance by raising cellular ROS levels above the cytotoxic threshold.
    Journal • PARP Biomarker
    |
    TNFA (Tumor Necrosis Factor-Alpha) • NQO1 (NAD(P)H dehydrogenase, quinone 1) • HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
    |
    gamitrinib
    2years
    Loss of function of CDK7 is synthetically lethal with fatty acid oxidation inhibition in glioblastoma (SNO 2022)
    Consistently, the combination treatment of CDK7i inhibitors with blockers of FAO (etomoxir) or cellular respiration (gamitrinib) exerted substantial synergistic growth inhibition in patient derived xenograft as well as neurosphere GBM cultures, which was mainly driven by a collapse of oxidative energy metabolism. Finally, the combined administration of YKL-5-124 and etomoxir extended overall in an orthotopic patient-derived xenograft model of GBM. In summary, these data support that simultaneous targeting of CDK7 and FAO might be a potential novel therapy against GBM.
    Synthetic lethality
    |
    MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1) • CDK7 (Cyclin Dependent Kinase 7)
    |
    etomoxir (MIQ-001) • gamitrinib
    almost3years
    Metabolic targeting of NRF2 potentiates the efficacy of TRAP1 inhibitor GTPP in colorectal cancer (AACR 2022)
    Inhibition of TRAP1 by a small molecule inhibitor, Gamitrinib-triphenylphosphonium (GTPP), in colon cancer cells led to ROS production, ER stress, reduction of cell viability and induction of cell death...These new findings for the first-time link TRAP1 and NRF2 in a common pathway regulating ROS production in colon cancer. Taken together, dual targeting of TRAP1 and NRF2 may potentially overcome the tumor cell resistance through disruption of mitochondrial redox homeostasis.
    Clinical
    |
    TNFA (Tumor Necrosis Factor-Alpha) • NQO1 (NAD(P)H dehydrogenase, quinone 1) • HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
    |
    gamitrinib