QBS10072S dihydrochloride

QBS10072S dihydrochloride is a bifunctional chemotherapeutic agent capable of penetrating the blood-brain barrier (BBB), featuring a LAT1-targeted domain and a cytotoxic domain. Its inhibitory potency on LAT1-mediated substrate uptake (IC50 = 21 μM) is approximately 50 times greater than on LAT2 (IC50 = 1100 μM). QBS10072S dihydrochloride enters tumor cells expressing LAT1 through LAT1-mediated active transport, resulting in DNA interstrand cross-linking, DNA damage, and cell death. This compound is applicable in research on glioblastoma and aggressive T-cell lymphoma.

QBS10072S dihydrochloride results in a dose-dependent viability loss in glioblastoma (GBM) cell lines such as U251, LN229, 8MGBA, 42MGBA, DBTRG, and AM38, with EC50 values ranging from 5.0 to 40 μM, when treated for 30 minutes. Additionally, after a 16-hour treatment, it induces dose-dependent DNA damage in U251 and LN229 GBM cells, while showing no effect on normal human astrocytes (NHA). Over a one-week period, QBS10072S dihydrochloride decreases survival rates in LAT1-positive T-cell lymphoma cell lines (H9, HH, MJ, and Hut78) in a dose-dependent manner, with IC50 values ranging from 4.4 μM for Hut78 to 51 μM for HH.

QBS10072S dihydrochloride, administered at a dosage of 10 mg/kg via intravenous injection once weekly for 4-6 weeks, is effective in inhibiting the growth of U251 GBM tumors. Additionally, QBS10072S at doses ranging from 2-8 mg/kg, given intravenously every two weeks for a total of three doses, suppresses tumor growth in LN229 glioblastoma (GBM) models. In an H9T cell lymphoma xenograft mouse model, QBS10072S (8 mg/kg) dihydrochloride demonstrates significant antitumor activity.