BGC0222 is a novel Irinotecan prodrug. As a PEG-cRGD conjugated derivative of Irinotecan, BGC0222 enables the slow and steady release of Irinotecan. It binds to the αVβ3 target with an IC50 of 4.25 μM and has an IC50 of 58.7 μM for αVβ5. BGC0222 can induce angiogenesis and demonstrates significant antitumor activity in various tumors.

BGC0222 (72 h) demonstrates superior antiproliferative activity against HT29, MIA PaCa-2, and MCF-7 tumor cells compared to Irinotecan and NKTR-102, with IC 50 values of 1.83 μM, 3.95 μM, and 0.68 μM, respectively. Additionally, BGC0222 (40 μM) exhibits significant angiogenic activity, achieving a vessel length of 1930 mm (CAM angiogenesis assay).

BGC0222 demonstrates significant antiproliferative activity in HT-29, MIA PaCa-2, NCI-H446, U-87 MG, and MDA-MB-231 xenograft models in nude mice when administered intravenously at doses of 20-60 mg/kg every four days or once weekly for three cycles, with RTV and T/C values both lower than those of Irinotecan. In Sprague-Dawley rats, BGC0222 at 30-90 mg/kg administered intravenously once weekly for 28 days exhibits improved safety compared to Irinotecan, with a maximum tolerated dose (MTD) of 90 mg/kg, exceeding Irinotecan's MTD of less than 60 mg/kg. Additionally, a single intravenous dose of BGC0222 (20-80 mg/kg) in Sprague-Dawley rats results in a slow and steady release of Irinotecan.