{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T14:54:38Z","timestamp":1789916078178,"version":"4.0.1"},"reference-count":74,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T00:00:00Z","timestamp":1705968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"French ministry of higher education and research"},{"name":"Canc\u00e9rop\u00f4le Grand Sud-Ouest"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Among the vinca-alkaloid class, vincristine is a potent chemotherapeutic agent with significant neurotoxic effects and is employed to address a wide spectrum of cancer types. Recently, the therapeutic potential of the cholecystokinin type 2 receptor (CCK2R) as a target for vincristine-induced peripheral neuropathy (VIPN) was demonstrated. In this study, the impact of preventive CCK2R blockade using netazepide (Trio Medicines Ltd., London, UK) was investigated in a mouse model of vincristine-induced peripheral neuropathy. Netazepide is a highly selective CCK2R antagonist under development for the treatment of patients with gastric neuroendocrine tumors caused by hypergastrinemia secondary to chronic autoimmune atrophic gastritis. Vincristine-induced peripheral neuropathy was induced by intraperitoneal injections of vincristine at 100 \u00b5g\/kg\/d for 7 days (D0 to D7). Netazepide (2 mg\/kg\/d or 5 mg\/kg\/d, per os) was administered one day before vincristine treatment until D7. Vincristine induced a high tactile allodynia from D1 to D7. VIPN was characterized by dorsal root ganglion neuron (DRG) and intraepidermal nerve fiber (IENF) loss, and enlargement and loss of myelinated axons in the sciatic nerve. Netazepide completely prevented the painful symptoms and nerve injuries induced by vincristine. In conclusion, the fact that netazepide protected against vincristine-induced peripheral neuropathy in a mouse model strongly supports the assessment of its therapeutic potential in patients receiving such chemotherapy.<\/jats:p>","DOI":"10.3390\/ph17020144","type":"journal-article","created":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T04:17:40Z","timestamp":1705983460000},"page":"144","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Netazepide, an Antagonist of Cholecystokinin Type 2 Receptor, Prevents Vincristine-Induced Sensory Neuropathy in Mice"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9043-3947","authenticated-orcid":false,"given":"Amandine","family":"Bernard","sequence":"first","affiliation":[{"name":"NeurIT Neuropathies et Innovations Th\u00e9rapeutiques UR 20218, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3805-3872","authenticated-orcid":false,"given":"Mohamad","family":"Mrou\u00e9","sequence":"additional","affiliation":[{"name":"NeurIT Neuropathies et Innovations Th\u00e9rapeutiques UR 20218, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Bourthoumieu","sequence":"additional","affiliation":[{"name":"NeurIT Neuropathies et Innovations Th\u00e9rapeutiques UR 20218, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, France"},{"name":"Department of Cytogenetic, Medical Genetic and Reproduction Biology, University Hospital of Limoges, 87042 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm","family":"Boyce","sequence":"additional","affiliation":[{"name":"Hammersmith Medicines Research Limited and Trio Medicines Limited, 44 Cumberland Avenue, London NW10 7EW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Richard","sequence":"additional","affiliation":[{"name":"NeurIT Neuropathies et Innovations Th\u00e9rapeutiques UR 20218, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, France"},{"name":"Department of Neurology, Reference Center for Rare Peripheral Neuropathies, University Hospital of Limoges, 87042 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6428-5162","authenticated-orcid":false,"given":"Franck","family":"Sturtz","sequence":"additional","affiliation":[{"name":"NeurIT Neuropathies et Innovations Th\u00e9rapeutiques UR 20218, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, France"},{"name":"Department of Biochemistry and Molecular Genetics, University Hospital of Limoges, 87042 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6199-4534","authenticated-orcid":false,"given":"Claire","family":"Demiot","sequence":"additional","affiliation":[{"name":"NeurIT Neuropathies et Innovations Th\u00e9rapeutiques UR 20218, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, France"},{"name":"Transversal and Territorial Therapeutic Education Unit (UTTEP87), University Hospital of Limoges, 87042 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6266-7690","authenticated-orcid":false,"given":"Aurore","family":"Danigo","sequence":"additional","affiliation":[{"name":"NeurIT Neuropathies et Innovations Th\u00e9rapeutiques UR 20218, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/jns.12114","article-title":"Patterns and Severity of Vincristine-Induced Peripheral Neuropathy in Children with Acute Lymphoblastic Leukemia","volume":"20","author":"Li","year":"2015","journal-title":"J. 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