TKL002 is a blood-brain barrier-permeable inhibitor of the CTH/H 2 S/NF-κB/EMT signaling axis. TKL002 induces G 2 /M phase cell cycle arrest and apoptosis in glioblastoma cells. TKL002 inhibits the migration and invasion of glioblastoma cells by upregulating E-cadherin and downregulating N-cadherin and vimentin. TKL002 is applicable to relevant research on glioblastoma [1].
In Vivo, TKL002 (5-20 mg/kg; i.p.; once every other day, 7 total administrations) inhibits the growth of subcutaneous glioblastoma xenografts in a dose-dependent manner[1]. TKL002 (10-20 mg/kg; i.v., once every three days for a total of 5 administrations) can cross the blood-brain barrier, inhibit the growth of orthotopic glioblastoma in a dose-dependent manner, reduce tumor burden, maintain the physical condition of mice, and cause no obvious organ toxicity[1].
In Vitro, TKL002 (0.625-10 μmol/L; 24-72 h) potently inhibits the proliferation of U87MG, U118MG, and U251MG glioblastoma cells in a dose- and time-dependent manner with selectivity over normal LX2 cells, exhibiting IC50 values ranging from 4.141 to 6.506 μmol/L across cell lines and time points[1]. TKL002 (6 μmol/L; 48 h) induces late apoptosis in U87MG glioblastoma cells, mediated via upregulation of Bax and caspase-3 and downregulation of Bcl-2 and active-caspase-3[1]. TKL002 (2-6 μmol/L; 24 h) induces G2/M phase cell cycle arrest in U87MG and U118MG glioblastoma cells in a concentration-dependent manner, with maximum G2/M fractions of 22.68% and 30.31% at 6 μmol/L respectively[1]. TKL002 (2-6 μmol/L; 48 h) reduces CTH, cysteine, and H2S levels, increases GSH levels, and inhibits NF-κB signaling and pro-inflammatory cytokine expression in U87MG and U118MG glioblastoma cells in vitro in a dose-dependent manner[1]. TKL002 (2-6 μmol/L; 48 h) inhibits migration and invasion of U87MG and U118MG glioblastoma cells in a dose-dependent manner, mediated via upregulation of E-cadherin and downregulation of N-cadherin and vimentin to suppress epithelial-mesenchymal transition[1].
References:
[1]. Luo Z, et al. Hijacking the Hydrogen Sulfide Axis: A Novel 4-Trifluoromethylquinoline Derivative Suppresses Glioblastoma via Cystathionine γ-Lyase Suppression. J Med Chem. 2026;69(3):3457-3476.
In Vivo, TKL002 (5-20 mg/kg; i.p.; once every other day, 7 total administrations) inhibits the growth of subcutaneous glioblastoma xenografts in a dose-dependent manner[1]. TKL002 (10-20 mg/kg; i.v., once every three days for a total of 5 administrations) can cross the blood-brain barrier, inhibit the growth of orthotopic glioblastoma in a dose-dependent manner, reduce tumor burden, maintain the physical condition of mice, and cause no obvious organ toxicity[1].
In Vitro, TKL002 (0.625-10 μmol/L; 24-72 h) potently inhibits the proliferation of U87MG, U118MG, and U251MG glioblastoma cells in a dose- and time-dependent manner with selectivity over normal LX2 cells, exhibiting IC50 values ranging from 4.141 to 6.506 μmol/L across cell lines and time points[1]. TKL002 (6 μmol/L; 48 h) induces late apoptosis in U87MG glioblastoma cells, mediated via upregulation of Bax and caspase-3 and downregulation of Bcl-2 and active-caspase-3[1]. TKL002 (2-6 μmol/L; 24 h) induces G2/M phase cell cycle arrest in U87MG and U118MG glioblastoma cells in a concentration-dependent manner, with maximum G2/M fractions of 22.68% and 30.31% at 6 μmol/L respectively[1]. TKL002 (2-6 μmol/L; 48 h) reduces CTH, cysteine, and H2S levels, increases GSH levels, and inhibits NF-κB signaling and pro-inflammatory cytokine expression in U87MG and U118MG glioblastoma cells in vitro in a dose-dependent manner[1]. TKL002 (2-6 μmol/L; 48 h) inhibits migration and invasion of U87MG and U118MG glioblastoma cells in a dose-dependent manner, mediated via upregulation of E-cadherin and downregulation of N-cadherin and vimentin to suppress epithelial-mesenchymal transition[1].
References:
[1]. Luo Z, et al. Hijacking the Hydrogen Sulfide Axis: A Novel 4-Trifluoromethylquinoline Derivative Suppresses Glioblastoma via Cystathionine γ-Lyase Suppression. J Med Chem. 2026;69(3):3457-3476.