Minigastrin Derivates, in Particular for Use in Cck2 Receptor Positive Tumour Diagnosis And/or Treatment

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This patent describes new derivatives of minigastrin peptides, which are specially modified to improve their effectiveness in diagnosing and treating tumors that have high expression of the CCK2 receptor (such as certain thyroid, lung, and ovarian cancers). By replacing specific amide bonds in the peptide structure with stable triazole rings and optionally substituting certain amino acids, these minigastrin derivatives show better accumulation in tumors, reduced uptake in non-target organs (especially kidneys), and improved stability. These peptides can be tagged with diagnostic or therapeutic agents (such as radionuclides or chemotherapeutic drugs) for targeted imaging or therapy of CCK2R-positive tumors.

Use CasesContent extracted from patent full text and abstract with AI.

• Targeted imaging of CCK2R-positive tumors using radiolabeled minigastrin derivatives in nuclear medicine (e.g., PET or SPECT scans).
• Treatment of CCK2R-expressing cancers (such as medullary thyroid carcinoma, small cell lung cancer, or stromal ovarian tumors) using radiolabeled or drug-conjugated minigastrin derivatives for precision therapy.
• Combination therapy, where the minigastrin derivative delivers both a diagnostic agent and a therapeutic compound (theranostics), allowing for monitoring and treatment of the cancer.
• Use in nanoparticles or liposomes for multimodal imaging or for delivering a combination of drugs specifically to tumor sites, sparing healthy tissue.
• Replacement of oxidizable amino acids in therapeutic peptides to increase their clinical stability, shelf-life, and effectiveness.

BenefitsContent extracted from patent full text and abstract with AI.

• Highly specific targeting and internalization in CCK2R-positive tumor cells, increasing the selectivity and efficacy of diagnosis and therapy.
• Reduced accumulation in healthy organs such as kidneys, minimizing toxicity and adverse effects.
• Improved plasma and metabolic stability of the peptides due to triazole substitution, leading to longer-lasting activity in the body.
• Versatile platform for attaching various imaging, therapeutic, or optical agents, enabling tailored diagnostic or therapeutic approaches for different clinical needs.
• Potential to overcome limitations of previous minigastrin derivatives, such as poor stability or kidney toxicity, thus enabling wider clinical adoption in oncology.

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Inventors & Applicants

Patent Abstract

It is therefore the objective of the present invention to provide minigastrin derivates which further improve the accumulation in CCK-2 receptor positive tumours by simultaneously very low accumulation in other organs, e.g. the kidneys. This objective is achieved according to the present invention by a minigastrin derviate having the formula: X-Z-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH 2 (Y), wherein at least one of the connecting or terminal amide bonds between, before or after the amino acids of the sequence Z, Ala, Tyr, Gly, Trp, Met, Asp, Phe and NH 2 or Y (C-terminal) is replaced by a 1,4-disubstituted or a 1,5-disubstituted 1,2,3-triazole, while X stands for a chemical group attached to the peptide for the purpose of diagnostic and/or therapeutic intervention at CCK-2 receptor relevant diseases, Y stands for C-terminal modifications of the peptide, such as amide, primary and secondary amides, free carboxylic acids and carboxylic ester derivatives including but not limited to amides and esters derived from linear or branched alkyl-,alkenyl-, alkynyl- aromatic-, and heterocyclic alcohols, and Z stands for a linker or DGlu* wherein DGlu* stands for a chain of DGlu having 1 to 6 repetitions (-DGlu- to -DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-). These minigastrin derivates have a high specific internalization, excellent IC 50 values and sufficient plasma stability.