QBS10072S dihydrochloride is a LAT1 -selective substrate with blood-brain barrier permeability that inhibits tumor growth. QBS10072S dihydrochloride enters LAT1-expressing tumor cells via LAT1-mediated active transport, induces interstrand DNA cross-linking and cell apoptosis, and reduces leptomeningeal dissemination. QBS10072S dihydrochloride can be used in studies related to glioblastoma multiforme, diffuse intrinsic pontine glioma, triple-negative breast cancer brain metastases, and aggressive T-cell lymphoma [1] [2] [3].
In Vivo, QBS10072S (10 mg/kg; i.v.; once a week; 8 weeks) dihydrochloride produces highly significant tumor growth inhibition in a subcutaneous TNBC xenograft model with no obvious toxicity[2]. QBS10072S (8 mg/kg; i.v.; once a week; 9 weeks; i.p.; twice a week; 9 weeks) dihydrochloride significantly reduces intracranial tumor growth, extends survival, and decreases leptomeningeal dissemination in a TNBC brain metastasis model with no obvious toxicity[2].
In Vitro, QBS10072S dihydrochloride induces significant cytotoxicity in LAT1-expressing GBM cell lines (including those with high and low MGMT expression) and minimal cytotoxicity in LAT1-negative normal human astrocytes[1]. QBS10072S dihydrochloride is preferentially cytotoxic to human TNBC cell lines (MDA-MB-157, MDA-MB-468, HCC1806, DU4475, MDA-MB-231-BR3, MDA-MB-231, HCC1937, BT-549) with LC50 values of 1 to 10 μM, while human ER-positive breast cancer cell lines (MCF-7, EMT6) are less sensitive[2]. QBS10072S (log[QBS] = -9 to log[QBS] = -3) dihydrochloride induces dose-dependent cytotoxicity in human TNBC MDA-MB-231 cells[2]. QBS10072S dihydrochloride induces dose-dependent cytotoxicity in LAT1-positive Hut78, HH, MJ, and H9 T-cell lymphoma cell lines[3].
References:
[1]. Ozawa T, et al. A Novel Blood-Brain Barrier-Permeable Chemotherapeutic Agent for the Treatment of Glioblastoma. Cureus. 2021;13(8):e17595. Published 2021 Aug 31.
[2]. Murga-Zamalloa C, et al. Successful anti-tumor effects with two novel bifunctional chemotherapeutic compounds that combine a LAT1 substrate with cytotoxic moieties in aggressive T-cell lymphomas. Leuk Res Rep. 2023;21:100398. Published 2023 Nov 22.
In Vivo, QBS10072S (10 mg/kg; i.v.; once a week; 8 weeks) dihydrochloride produces highly significant tumor growth inhibition in a subcutaneous TNBC xenograft model with no obvious toxicity[2]. QBS10072S (8 mg/kg; i.v.; once a week; 9 weeks; i.p.; twice a week; 9 weeks) dihydrochloride significantly reduces intracranial tumor growth, extends survival, and decreases leptomeningeal dissemination in a TNBC brain metastasis model with no obvious toxicity[2].
In Vitro, QBS10072S dihydrochloride induces significant cytotoxicity in LAT1-expressing GBM cell lines (including those with high and low MGMT expression) and minimal cytotoxicity in LAT1-negative normal human astrocytes[1]. QBS10072S dihydrochloride is preferentially cytotoxic to human TNBC cell lines (MDA-MB-157, MDA-MB-468, HCC1806, DU4475, MDA-MB-231-BR3, MDA-MB-231, HCC1937, BT-549) with LC50 values of 1 to 10 μM, while human ER-positive breast cancer cell lines (MCF-7, EMT6) are less sensitive[2]. QBS10072S (log[QBS] = -9 to log[QBS] = -3) dihydrochloride induces dose-dependent cytotoxicity in human TNBC MDA-MB-231 cells[2]. QBS10072S dihydrochloride induces dose-dependent cytotoxicity in LAT1-positive Hut78, HH, MJ, and H9 T-cell lymphoma cell lines[3].
References:
[1]. Ozawa T, et al. A Novel Blood-Brain Barrier-Permeable Chemotherapeutic Agent for the Treatment of Glioblastoma. Cureus. 2021;13(8):e17595. Published 2021 Aug 31.
[2]. Murga-Zamalloa C, et al. Successful anti-tumor effects with two novel bifunctional chemotherapeutic compounds that combine a LAT1 substrate with cytotoxic moieties in aggressive T-cell lymphomas. Leuk Res Rep. 2023;21:100398. Published 2023 Nov 22.