KGP18

KGP18 (3-methoxy-9-(3',4',5'-trimethoxyphenyl)-6,7-dihydro-5H-benzo[7]annulen-4-ol) is a synthetic, benzosuberene-based small molecule that acts as a potent inhibitor of tubulin polymerization and a vascular disrupting agent (VDA). Originally inspired by the natural products colchicine and combretastatin A-4 (CA4), KGP18 binds to the colchicine binding site on tubulin, leading to microtubule depolymerization and subsequent cytoskeletal disruption in rapidly proliferating endothelial cells. This disruption causes morphological changes in endothelial cells (from flat to round), leading to the collapse of established tumor-associated microvessels, shutdown of tumor blood flow, and central tumor necrosis. KGP18 was developed by Baylor University in collaboration with OXiGENE (later Mateon Therapeutics) and has been evaluated in preclinical models of various solid tumors, including breast, prostate, and lung cancers. To overcome its poor water solubility, a phosphorylated prodrug, KGP265, was developed to facilitate in vivo administration.

Other names

2-Methoxy-5-(3',4',5'-trimethoxyphenyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-ol3-methoxy-9-(3',4',5'-trimethoxyphenyl)-6,7-dihydro-5H-benzo[7]annulen-4-ol