Pip1

Pip1 is a synthetic, low molecular weight analog of piperine designed to overcome multi-drug resistance (MDR) in cancer. It specifically targets P-glycoprotein (P-gp/ABCB1), an ATP-binding cassette transporter that effluxes various chemotherapeutic drugs out of cancer cells, thereby reducing their efficacy. Pip1 was engineered by replacing the piperidine ring of piperine with a 6,7-dimethoxytetrahydroisoquinoline moiety, a structural feature also found in third-generation P-gp inhibitors. In preclinical studies, Pip1 has demonstrated the ability to significantly increase the sensitivity of resistant cervical (KB ChR 8–5) and colorectal (SW480-VCR) cancer cells to chemotherapeutic substrates such as vincristine, colchicine, and paclitaxel. By inhibiting P-gp-mediated efflux, Pip1 promotes the intracellular accumulation of these drugs, restoring their pro-apoptotic and cytotoxic effects in resistant cell populations.

Other names

(2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)penta-2,4-dien-1-one