ArticleCancers2022
OATD-02 Validates the Benefits of Pharmacological Inhibition of Arginase 1 and 2 in Cancer.
Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Metabolic reprogramming-mediated therapeutic resistance in renal cell carcinoma: Mechanisms and targeted intervention strategies.iScience · 2026Review
- The Biological Effects of Boron in Animals and Humans.Biological trace element research · 2026Review
- The competition of amino acid among tumors, tumor-associated macrophages and T cells based on metabolic reprogramming.iScience · 2026Review
- Review
- Hematopoietic Niche Hijacking in Bone Metastases: Roles of Megakaryocytes, Erythroid Lineage Cells, and Perivascular Stromal Subsets.Biomedicines · 2026Review
- The role of L-Arginine metabolism in the hallmarks of cancer as an emerging pathway to drug design.Frontiers in pharmacology · 2026Review
- Targeting MDSCs in cancer: emerging immunotherapeutic and metabolic strategies.Frontiers in immunology · 2026Review
- Integrating artificial intelligence into small molecule development for precision cancer immunomodulation therapy.npj drug discovery · 2025Review
- Immunotherapy resistance in non-small cell lung cancer: from mechanisms to therapeutic opportunities.Journal of experimental & clinical cancer research : CR · 2025Review
- Metabolomic reprogramming of the tumor microenvironment by dual arginase inhibitor OATD-02 boosts anticancer immunity.Scientific reports · 2025Article
- The roles of arginases and arginine in immunity.Nature reviews. Immunology · 2025Review
- Detrimental influence of Arginase-1 in infiltrating macrophages on poststroke functional recovery and inflammatory milieu.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Synthesis of Arginase Inhibitors: An Overview.Pharmaceutics · 2025Review
- Arginase-II promotes melanoma and lung cancer cell growth by regulating Sirt3-mtROS axis.Frontiers in cell and developmental biology · 2025Article
- General Commentary: The letter to editor" Immune-metabolic crosstalk in HNSCC: mechanisms and therapeutic opportunities".Frontiers in oncology · 2025Article
- Disrupting Notch signaling related HES1 in myeloid cells reinvigorates antitumor T cell responses.Experimental hematology & oncology · 2024Article
- Pathophysiology of Arginases in Cancer and Efforts in Their Pharmacological Inhibition.International journal of molecular sciences · 2024Review
- Targeting amino acid-metabolizing enzymes for cancer immunotherapy.Frontiers in immunology · 2024Review
- Facile synthesis of newRSC advances · 2023Article
- Dietary Manipulation of Amino Acids for Cancer Therapy.Nutrients · 2023Review
Corrections and comments
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19 authors.
Funding
Abstract
backgroundArginases play essential roles in metabolic pathways, determining the fitness of both immune and tumour cells. Along with the previously validated role of ARG1 in cancer, the particular significance of ARG2 as a therapeutic target has emerged as its levels correlate with malignant phenotype and poor prognosis. These observations unveil arginases, and specifically ARG2, as well-validated and promising therapeutic targets. OATD-02, a new boronic acid derivative, is the only dual inhibitor, which can address the benefits of pharmacological inhibition of arginase 1 and 2 in cancer.
methodsThe inhibitory activity of OATD-02 was determined using recombinant ARG1 and ARG2, as well as in a cellular system using primary hepatocytes and macrophages. In vivo antitumor activity was determined in syngeneic models of colorectal and kidney carcinomas (CT26 and Renca, respectively), as well as in an ARG2-dependent xenograft model of leukaemia (K562).
resultsOATD-02 was shown to be a potent dual (ARG1/ARG2) arginase inhibitor with a cellular activity necessary for targeting ARG2. Compared to a reference inhibitor with predominant extracellular activity towards ARG1, we have shown improved and statistically significant antitumor efficacy in the CT26 model and an immunomodulatory effect reflected by Treg inhibition in the Renca model. Importantly, OATD-02 had a superior activity when combined with other immunotherapeutics. Finally, OATD-02 effectively inhibited the proliferation of human K562 leukemic cells both in vitro and in vivo.
conclusionsOATD-02 is a potent small-molecule arginase inhibitor with optimal drug-like properties, including PK/PD profile. Excellent activity against intracellular ARG2 significantly distinguishes OATD-02 from other arginase inhibitors. OATD-02 represents a very promising drug candidate for the combined treatment of tumours, and is the only pharmacological tool that can effectively address the benefits of ARG1/ARG2 inhibition. OATD-02 will enter clinical trials in cancer patients in 2022.
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