ArticleMolecular cancer therapeutics2021
Identification and Characterization of IMD-0354 as a Glutamine Carrier Protein Inhibitor in Melanoma.
Article in Molecular cancer therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Ferroptosis-Mediated Cell-Specific Damage: Molecular Cascades and Therapeutic Breakthroughs in Diabetic Retinopathy.Antioxidants (Basel, Switzerland) · 2025Review
- MRI of ASCT2-mediated amino acid uptake in xenograft tumor models.Research square · 2025Article
- Artemisia annua-derived extracellular vesicles reprogram breast tumor immune microenvironment via altering macrophage polarization and synergizing recruitment of T lymphocytes.Chinese medicine · 2025Article
- Recent advances in ASCT2 inhibitors: ligand design and therapeutic applications.Future medicinal chemistry · 2025Review
- Mitochondrial Metabolomics in Cancer: Mass Spectrometry-Based Approaches for Metabolic Rewiring Analysis and Therapeutic Discovery.Metabolites · 2025Review
- Effects of circulating RNAs on tumor metabolism in lung cancer (Review).Oncology letters · 2025Review
- Glutamine metabolism and ammonia death: targeted modulation for enhanced cancer immunotherapy.Frontiers in immunology · 2025Review
- Overcoming Cancer Persister Cells by Stabilizing the ATF4 Promoter G-quadruplex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Exploiting the Achilles' heel of cancer: disrupting glutamine metabolism for effective cancer treatment.Frontiers in pharmacology · 2024Review
- Inhibition of NF-κB ameliorates aberrant retinal glia activation and inflammatory responses in streptozotocin-induced diabetic rats.Annals of translational medicine · 2023Article
- Autophagy Paradox: Strategizing Treatment Modality in Melanoma.Current treatment options in oncology · 2023Review
- Salicylanilides and Their Anticancer Properties.International journal of molecular sciences · 2023Review
- Tea Tree Oil Mediates Antioxidant Factors Relish and Nrf2-Autophagy Axis Regulating the Lipid Metabolism ofAntioxidants (Basel, Switzerland) · 2022Article
- Antitumor activity of mianserin (a tetracyclic antidepressant) primarily driven by the inhibition of SLC1A5-mediated glutamine transport.Investigational new drugs · 2022Article
- Targeting of Ubiquitin E3 Ligase RNF5 as a Novel Therapeutic Strategy in Neuroectodermal Tumors.Cancers · 2022Article
- NF-κB and its crosstalk with endoplasmic reticulum stress in atherosclerosis.Frontiers in cardiovascular medicine · 2022Review
- Norcantharidin overcomes vemurafenib resistance in melanoma by inhibiting pentose phosphate pathway and lipogenesisFrontiers in pharmacology · 2022Article
- Connections between metabolism and epigenetic modifications in cancer.Medical review (2021) · 2021Review
- The Uniqueness of Clear Cell Renal Cell Carcinoma: Summary of the Process and Abnormality of Glucose Metabolism and Lipid Metabolism in ccRCC.Frontiers in oncology · 2021Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
A key hallmark of cancer, altered metabolism, is central to cancer pathogenesis and therapy resistance. Robust glutamine metabolism is among cellular processes regulating tumor progression and responsiveness to therapy in a number of cancers, including melanoma and breast cancer. Among mechanisms underlying the increase in glutamine metabolism in tumors is enhanced glutamine uptake mediated by the glutamine transporters, with SLC1A5 (also known as ASCT2) shown to play a predominant role. Correspondingly, increased SLC1A5 expression coincides with poorer survival in patients with breast cancer and melanoma. Therefore, we performed an image-based screen to identify small molecules that are able to prevent the localization of SLC1A5 to the plasma membrane without impacting cell shape. From 7,000 small molecules, nine were selected as hits, of which one (IMD-0354) qualified for further detailed functional assessment. IMD-0354 was confirmed as a potent inhibitor of glutamine uptake that attained sustained low intracellular glutamine levels. Concomitant with its inhibition of glutamine uptake, IMD-0354 attenuated mTOR signaling, suppressed two- and three-dimensional growth of melanoma cells, and induced cell-cycle arrest, autophagy, and apoptosis. Pronounced effect of IMD-0354 was observed in different tumor-derived cell lines, compared with nontransformed cells. RNA-sequencing analysis identified the unfolded protein response, cell cycle, and response (DNA damage response pathways) to be affected by IMD-0354. Combination of IMD-0354 with GLS1 or LDHA inhibitors enhanced melanoma cell death.
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