MBL-II-141 is a potent ABCG2 inhibitor with an IC50 of 0.11 μM. It inhibits the transport function of ABCG2 in a non-competitive manner, preventing ABCG2 from expelling substrates (such as Irinotecan) out of cells, thereby increasing the intracellular accumulation of the drug. MBL-II-141 does not affect ABCB1 (P-gp) or ABCC1 (MRP1) and exhibits very low cytotoxicity (IG50 > 100 μM). This compound is useful for studying tumor multidrug resistance (MDR).

MBL-II-141, administered at 10 mg/kg through intraperitoneal injections three times a week for a period of 50-87 days, in combination with the anticancer drug Irinotecan (CPT-11), effectively suppresses the growth of 90% of freshly implanted ABCG2-positive tumors. A single dose of MBL-II-141 (10 mg/kg, intraperitoneal injection) reduces the total apparent clearance and biliary clearance of Irinotecan while significantly enhancing the exposure of Irinotecan and SN-38 in blood and brain tissue. Moreover, MBL-II-141, at doses ranging from 10-50 mg/kg administered either intraperitoneally or orally, exhibits a relatively high predicted LD50 (intraperitoneal: 290 mg/kg, oral: 1200 mg/kg), with experiments confirming no significant toxicity or tissue damage even at doses up to 50 mg/kg.