IGF-methotrexate conjugate

IGF-methotrexate conjugate (IGF-MTX) is a novel targeted antineoplastic agent consisting of the antifolate chemotherapy drug methotrexate covalently linked to a variant of insulin-like growth factor 1 (long-R3-IGF-1 or 765IGF). This design enables selective delivery of methotrexate to tumor cells that overexpress the insulin-like growth factor type 1 receptor (IGF-1R), which is common in various malignancies including myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and several solid tumors. The long-R3 variant has high affinity for IGF-1R but reduced binding to circulating IGFBPs, enhancing tumor targeting. Mechanistically, the drug acts as an inhibitor of tetrahydrofolate dehydrogenase and thymidylate synthase via its methotrexate component. Preclinical studies demonstrated significantly greater efficacy and lower toxicity compared to free methotrexate. Clinical trials have shown that IGF-MTX is well tolerated with minimal cytopenias and promising activity in heavily pretreated patients with advanced cancers[2][4][5][7][9].

Other names

long-R3-IGF-1-methotrexate conjugatelong-R-3-IGF-1-methotrexate conjugatelong-R 3-IGF-1-methotrexate conjugate