LD-110 triTFA is a highly efficient and effective LSD1 PROTAC degrader ( DC50 = 0.44 μM). LD-110 triTFA promotes LSD1 degradation and increases the level of H3K4 dimethylation in a ubiquitin-proteasome-dependent manner. LD-110 triTFA inhibits the growth and survival of multiple esophagus squamous cancer cell (ESCC) lines by inducing apoptosis. LD-110 triTFA can be used for the study of esophagus squamous cancer [1]. (Pink: LSD1 ligand; Blue: Cereblon ligand; Black: linker).
In Vivo, LD-110 (30 mg/kg, 100 mg/kg, i.p., once daily for 24 days) triTFA exhibits potent dose-dependent antitumor activity in the KYSE-150 xenograft mice model without causing significant toxicity[1].
In Vitro, LD-110 (1-10 μM) triTFA, with a linker containing four methylene groups, demonstrates good degradation activity, achieving degradation rates of 65, 70, and 84% against the LSD1 protein at concentrations of 1, 3, and 10 μM, respectively[1]. LD-110 (0.1-30 μM, 6-72 h) triTFA effectively and dose-dependently degrades LSD1 protein, achieving near-complete depletion within 48-72 hours with DC50 values of 0.44, 1.18, and 1.24 μM in KYSE-150, KYSE-30, and EC9706 ESCC cells, respectively; this degradation is highly specific with minimal effect on CoREST/HDAC1/HDAC2 levels, and consequently leads to a potent 2 to 7-fold accumulation of H3K4me2[1]. LD-110 (72 h) triTFA effectively suppresses the growth of ESCC cells with half-maximal inhibitory concentration (IC50) values of 3.94, 3.35, and 3.08 μM in KYSE-150, KYSE-30, and EC9706, respectively[1]. LD-110 (3-10 μM, 10-14 days) triTFA can effectively inhibit the proliferation of ESCC KYSE-30 and EC9706 cells[1]. LD-110 (3-10 μM, 48 h) triTFA dose-dependently induces both early-stage and late-stage apoptosis and causes cleavage of PARP and caspase-3 in KYSE-30 and EC9706 cells[1].
References:
[1]. Zhuo J, et al. Discovery of LD-110 as an Effective LSD1 PROTAC Degrader for the Treatment of Esophagus Squamous Cancer. J Med Chem. 2025 Oct 23;68(20):21860-21877.
In Vivo, LD-110 (30 mg/kg, 100 mg/kg, i.p., once daily for 24 days) triTFA exhibits potent dose-dependent antitumor activity in the KYSE-150 xenograft mice model without causing significant toxicity[1].
In Vitro, LD-110 (1-10 μM) triTFA, with a linker containing four methylene groups, demonstrates good degradation activity, achieving degradation rates of 65, 70, and 84% against the LSD1 protein at concentrations of 1, 3, and 10 μM, respectively[1]. LD-110 (0.1-30 μM, 6-72 h) triTFA effectively and dose-dependently degrades LSD1 protein, achieving near-complete depletion within 48-72 hours with DC50 values of 0.44, 1.18, and 1.24 μM in KYSE-150, KYSE-30, and EC9706 ESCC cells, respectively; this degradation is highly specific with minimal effect on CoREST/HDAC1/HDAC2 levels, and consequently leads to a potent 2 to 7-fold accumulation of H3K4me2[1]. LD-110 (72 h) triTFA effectively suppresses the growth of ESCC cells with half-maximal inhibitory concentration (IC50) values of 3.94, 3.35, and 3.08 μM in KYSE-150, KYSE-30, and EC9706, respectively[1]. LD-110 (3-10 μM, 10-14 days) triTFA can effectively inhibit the proliferation of ESCC KYSE-30 and EC9706 cells[1]. LD-110 (3-10 μM, 48 h) triTFA dose-dependently induces both early-stage and late-stage apoptosis and causes cleavage of PARP and caspase-3 in KYSE-30 and EC9706 cells[1].
References:
[1]. Zhuo J, et al. Discovery of LD-110 as an Effective LSD1 PROTAC Degrader for the Treatment of Esophagus Squamous Cancer. J Med Chem. 2025 Oct 23;68(20):21860-21877.