TKL002 is a blood-brain barrier-permeable inhibitor of the CTH/H₂S/NF-κB/EMT signaling axis. It induces G2/M phase cell cycle arrest and apoptosis in glioblastoma cells. TKL002 also inhibits the migration and invasion of glioblastoma cells by upregulating E-cadherin and downregulating N-cadherin and vimentin expression, and is used in glioblastoma research.

Methods: U87MG, U118MG, U251MG glioblastoma cells and normal LX2 cells were treated with 0.625–10 μM TKL002 for 24–72 hours. Indicators related to proliferation, apoptosis, cell cycle, hydrogen sulfide metabolism, inflammatory pathways, migration and invasion were detected.
Results:
1.TKL002 potently inhibited the proliferation of glioblastoma cells in a dose- and time-dependent manner, and showed selectivity for normal LX2 cells, with an IC₅₀ of 4.141–6.506 μM.
2.TKL002 (6 μM, 48 h) could induce late apoptosis of U87MG cells, which was achieved by up-regulating Bax and caspase-3, and down-regulating Bcl-2 and activated caspase-3.
3.TKL002 (2–6 μM, 24 h) induced G2/M phase cell cycle arrest in U87MG and U118MG cells in a concentration-dependent manner.
4.TKL002 (2–6 μM, 48 h) could reduce the levels of CTH, cysteine and H₂S, increase the level of GSH, and dose-dependently inhibit the NF-κB pathway and the expression of pro-inflammatory factors.
5.TKL002 (2–6 μM, 48 h) dose-dependently inhibited cell migration and invasion, and suppressed epithelial-mesenchymal transition by up-regulating E-cadherin and down-regulating N-cadherin and vimentin [1].

Methods: TKL002 was administered to glioblastoma model mice: in the subcutaneous xenograft model, 5–20 mg/kg was injected intraperitoneally once every other day for a total of 7 times; in the orthotopic model, 10–20 mg/kg was injected intravenously once every 3 days for a total of 5 times. Indicators such as tumor growth, blood-brain barrier penetration and toxicity were detected.
Results:
1.TKL002 inhibited the growth of glioblastoma subcutaneous xenografts in a dose-dependent manner.
2.TKL002 could penetrate the blood-brain barrier, suppress the growth of orthotopic glioblastoma in a dose-dependent manner, reduce tumor burden, maintain the physical condition of mice, and showed no obvious organ toxicity [1].