An endothelin B receptor agonist
Route of Administration
Mode of Action
Figure 1. Schematic diagram showing mechanism of selective and transient increase in blood flow to tumors following treatment with SPI-16201,2
SPI-1620 is a highly selective peptide agonist of endothelin-B receptors expressed on endothelial cells lining the interior surface of blood vessels. By stimulating the endothelin-B receptors on tumor vasculature, SPI-1620 should transiently modify blood flow, and increase delivery of anticancer agents to the tumor.
Chemotherapy is one of the mainstays of therapy for solid carcinomas, including breast, lung, and prostate. Chemotherapy uses drugs called cytotoxic agents that are poisonous to cells and kill cancer cells, as well as rapidly dividing normal cells. Chemotherapy often fails because adequate and uniform distribution of the cytotoxic agents is not achieved in the tumor, and serious side effects can result from toxicity to normal cells. Consequently, any means to increase the delivery of a cytotoxic agent selectively to tumors, while minimizing its concentration in normal tissues may be very beneficial.
SPI-1620 is being developed as an adjunct to chemotherapy. In pre-clinical studies, when anti-cancer drugs, such as paclitaxel injection, are administered shortly after SPI-1620, the anti-cancer drug concentration in the tumor is increased several fold.
This results in increased antitumor efficacy at a given dose of a cytotoxic agent, and might allow physicians to maximize efficacy with reduced cytotoxic agent doses with resultant decreased toxicity to the normal organs.