TMLZ-G46 is an orally active ZNF207 inhibitor with blood-brain barrier penetration ability, with a K d value of 68 nM. TMLZ-G46 inhibits cancer cell proliferation, stemness, migration and invasion, induces G0/G1 cell cycle arrest and apoptosis, and suppresses colony formation. TMLZ-G46 can be used in glioma research [1].
In Vivo, TMLZ-G46 (60 mg/kg; p.o.; once daily; 28 days) achieves a tumor growth inhibition rate of 83.7% in mouse U251MG glioblastoma xenografts[1]. TMLZ-G46 (30 mg/kg; i.g.; once daily; 60 days) reduces tumor burden of orthotopic U251MG glioblastoma xenografts in mice and significantly prolongs their survival, with efficacy comparable to that of Temozolomide [1].
In Vitro, TMLZ-G46 (10 μM; 3 h) binds to ZNF207 in LN229 and U251MG glioma cells, and significantly increases the thermal stability of this protein[1]. TMLZ-G46 (72 h) potently inhibits the proliferation of glioma cell lines with high ZNF207 expression (LN229, U251MG, HS683, T98G), with IC50 values below 3 μM, while its activity decreases in cell lines with low ZNF207 expression (U87MG, U118MG, U138MG)[1]. TMLZ-G46 (0.25-4 μM; 14 days) potently impairs the clonogenic capacity of LN229 and U251MG glioma cells, with significant inhibitory effects observable at concentrations as low as 0.25 μM[1]. TMLZ-G46 (10 days) selectively inhibits the self-renewal of glioma stem-like cells in LN229 and U251MG cells, with an IC50 value at the submicromolar level[1]. TMLZ-G46 (0.5-4 μM; 24 h) dose-dependently inhibits the expression of SOX2 in LN229 and U251MG glioma cells, providing a basis for its inhibition of stem cell properties[1]. TMLZ-G46 (0-8 μM; 24-48 h) inhibits the migration and invasion abilities of LN229 and U251MG glioma cells in a dose-dependent manner[1]. TMLZ-G46 (1-5 μM; 24 h) induces G0/G1 cell cycle arrest and apoptosis in LN229 and U251MG glioma cells[1].
References:
[1]. Gao M, et al. Discovery, Optimization, and Biological Evaluation of 2-Cyano-2-(9 H -xanthen-9-ylidene)acetamide Derivatives as ZNF207 Inhibitors for Anti-Glioma Therapy. J Med Chem. Published online March 19, 2026.
In Vivo, TMLZ-G46 (60 mg/kg; p.o.; once daily; 28 days) achieves a tumor growth inhibition rate of 83.7% in mouse U251MG glioblastoma xenografts[1]. TMLZ-G46 (30 mg/kg; i.g.; once daily; 60 days) reduces tumor burden of orthotopic U251MG glioblastoma xenografts in mice and significantly prolongs their survival, with efficacy comparable to that of Temozolomide [1].
In Vitro, TMLZ-G46 (10 μM; 3 h) binds to ZNF207 in LN229 and U251MG glioma cells, and significantly increases the thermal stability of this protein[1]. TMLZ-G46 (72 h) potently inhibits the proliferation of glioma cell lines with high ZNF207 expression (LN229, U251MG, HS683, T98G), with IC50 values below 3 μM, while its activity decreases in cell lines with low ZNF207 expression (U87MG, U118MG, U138MG)[1]. TMLZ-G46 (0.25-4 μM; 14 days) potently impairs the clonogenic capacity of LN229 and U251MG glioma cells, with significant inhibitory effects observable at concentrations as low as 0.25 μM[1]. TMLZ-G46 (10 days) selectively inhibits the self-renewal of glioma stem-like cells in LN229 and U251MG cells, with an IC50 value at the submicromolar level[1]. TMLZ-G46 (0.5-4 μM; 24 h) dose-dependently inhibits the expression of SOX2 in LN229 and U251MG glioma cells, providing a basis for its inhibition of stem cell properties[1]. TMLZ-G46 (0-8 μM; 24-48 h) inhibits the migration and invasion abilities of LN229 and U251MG glioma cells in a dose-dependent manner[1]. TMLZ-G46 (1-5 μM; 24 h) induces G0/G1 cell cycle arrest and apoptosis in LN229 and U251MG glioma cells[1].
References:
[1]. Gao M, et al. Discovery, Optimization, and Biological Evaluation of 2-Cyano-2-(9 H -xanthen-9-ylidene)acetamide Derivatives as ZNF207 Inhibitors for Anti-Glioma Therapy. J Med Chem. Published online March 19, 2026.