caplostatin

Caplostatin is a macromolecular polymer-drug conjugate consisting of the angiogenesis inhibitor TNP-470 (a synthetic analog of fumagillin) covalently linked to an N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer. Developed by SynDevRx, Inc. based on research by Dr. Ronit Satchi-Fainaro, the drug is designed to inhibit angiogenesis by targeting multiple signaling pathways, including vascular endothelial growth factor receptor-2 (VEGFR-2), MAPK, and RhoA. The polymer conjugation increases the molecular weight of TNP-470, preventing it from crossing the blood-brain barrier and thereby mitigating the severe neurotoxicity (ataxia and depression) that previously halted the clinical development of the parent compound. Caplostatin is administered intravenously and has demonstrated the ability to inhibit vascular hyperpermeability and tumor growth in various preclinical models, including melanoma, breast, lung, and pancreatic cancers.

Other names

HPMA copolymer-TNP-470 conjugate