HLC40 is a MLL1 histone methyltransferase inhibitor with an IC50 of 0.82 μM by binding to WDR5. HLC40 inhibits proliferation of cancer cells, induces apoptosis and upregulates cleaved caspase-3 levels. HLC40 exhibits antitumor efficacy in a murine AML xenograft model [1].
In Vivo, HLC40 (20-30 mg/kg; i.p.; daily; 21 days) delivers significant dose-dependent antitumor efficacy in a murine MV4-11 xenograft model, achieving 49.1% tumor growth inhibition at 30 mg/kg with no observable toxicity[1].
In Vitro, HLC40 potently inhibits MLL1 histone methyltransferase activity in in vitro cell-free biochemical assay with an IC50 of 0.82 μM[1]. HLC40 potently and selectively inhibits proliferation of MV4-11 and MOLM-13 MLL-rearranged AML cells with IC50 values of 8.92 μM and 7.07 μM, respectively, while showing minimal activity against MLL wild-type K562 cells (IC50 = 49.68 μM)[1]. HLC40 exhibits minimal antagonistic activity against the CysLT1 receptor in stable HEK-293 cells, with an IC50 = 5.28 μM[1]. HLC40 (2.5-10 μM; 72 h) induces concentration-dependent apoptosis in MV4-11 and MOLM-13 MLL-rearranged AML cells, with apoptosis rates reaching up to 30.31% in MV4-11 cells at 10 μM[1]. HLC40 (0.625-10 μM; 24 h) activates the apoptotic pathway in MOLM-13 MLL-rearranged AML cells, as shown by concentration-dependent upregulation of cleaved caspase-3[1]. HLC40 (0.625-10 μM; 24 h) suppresses global H3K4 mono-, di-, and trimethylation in a concentration-dependent manner in MOLM-13 MLL-rearranged AML cells[1]. HLC40 (20 μM; 2 h) directly engages intracellular WDR5 in MOLM-13 MLL-rearranged AML cells, as evidenced by pronounced thermal stabilization of WDR5 at temperatures up to 61°C[1]. HLC40 (10 μM; 24 h) disrupts WDR5-mediated transcriptional activation in MV4-11 MLL-rearranged AML cells, suppressing proliferative programs and upregulating negative cell cycle regulators[1].
References:
[1]. He L, et al. Structure-based design of the approved drug zafirlukast identifies HLC40 as a potent WDR5 WIN-site inhibitor with antitumor efficacy. Bioorg Chem. 2026;176:109869.
In Vivo, HLC40 (20-30 mg/kg; i.p.; daily; 21 days) delivers significant dose-dependent antitumor efficacy in a murine MV4-11 xenograft model, achieving 49.1% tumor growth inhibition at 30 mg/kg with no observable toxicity[1].
In Vitro, HLC40 potently inhibits MLL1 histone methyltransferase activity in in vitro cell-free biochemical assay with an IC50 of 0.82 μM[1]. HLC40 potently and selectively inhibits proliferation of MV4-11 and MOLM-13 MLL-rearranged AML cells with IC50 values of 8.92 μM and 7.07 μM, respectively, while showing minimal activity against MLL wild-type K562 cells (IC50 = 49.68 μM)[1]. HLC40 exhibits minimal antagonistic activity against the CysLT1 receptor in stable HEK-293 cells, with an IC50 = 5.28 μM[1]. HLC40 (2.5-10 μM; 72 h) induces concentration-dependent apoptosis in MV4-11 and MOLM-13 MLL-rearranged AML cells, with apoptosis rates reaching up to 30.31% in MV4-11 cells at 10 μM[1]. HLC40 (0.625-10 μM; 24 h) activates the apoptotic pathway in MOLM-13 MLL-rearranged AML cells, as shown by concentration-dependent upregulation of cleaved caspase-3[1]. HLC40 (0.625-10 μM; 24 h) suppresses global H3K4 mono-, di-, and trimethylation in a concentration-dependent manner in MOLM-13 MLL-rearranged AML cells[1]. HLC40 (20 μM; 2 h) directly engages intracellular WDR5 in MOLM-13 MLL-rearranged AML cells, as evidenced by pronounced thermal stabilization of WDR5 at temperatures up to 61°C[1]. HLC40 (10 μM; 24 h) disrupts WDR5-mediated transcriptional activation in MV4-11 MLL-rearranged AML cells, suppressing proliferative programs and upregulating negative cell cycle regulators[1].
References:
[1]. He L, et al. Structure-based design of the approved drug zafirlukast identifies HLC40 as a potent WDR5 WIN-site inhibitor with antitumor efficacy. Bioorg Chem. 2026;176:109869.