ErSO-TFPy (TEQ103) is an ERα+ tumor cell inhibitor with low nanomolar cytotoxic activity against ERα+ breast cancer cells. ErSO-TFPy activates the sodium channel TRPM4, causes an imbalance of intracellular calcium and sodium ions. ErSO-TFPy dysregulates calcium homeostasis in ERα+ tumor cells, triggers the anticipatory unfolded protein response, and induces rapid immune cell-independent necrotic cell death. ErSO-TFPy can be used for the research of estrogen receptor alpha positive breast cancer [1] [2].
In Vivo, ErSO-TFPy (TEQ103) (1-150 mg/kg total dose; i.v.) exhibits significant, durable antitumor activity in MCF-7 tumor-bearing athymic female mice, with 100% tumor-free survivors achieved regardless of administration schedule[1]. ErSO-TFPy (2-10 mg/kg; i.v.; once weekly; 4 doses) induces complete regression of MCF-7 ERα+ breast cancer xenografts in athymic nude mice at 10 mg/kg, with significant tumor growth inhibition at 5 mg/kg, no significant inhibition at 2 mg/kg, and no significant weight loss[2]. ErSO-TFPy (20 mg/kg; i.v.; once or twice weekly; 4 doses) induces complete regression of Fulvestrant -resistant ST941 ESR1mut breast cancer PDX tumors in athymic nude mice[2]. ErSO-TFPy (2-50 mg/kg; i.v.; single dose) induces near-complete or complete regression of MCF-7 ESR1D538G breast cancer xenografts, including large ~1500 mm3 tumors, in athymic nude mice at 25 mg/kg or 50 mg/kg, with significant inhibition at 5 mg/kg and no significant inhibition at 2 mg/kg[2]. ErSO-TFPy (50 mg/kg; i.v.; single dose) induces significant regression of BT-474 ERα+/HER2+ breast cancer xenografts, including large established tumors, in athymic nude mice[2]. ErSO-TFPy (50 mg/kg; i.v.; single dose) induces rapid necrotic cell death in MCF-7 ESR1D538G breast cancer xenografts, with >90% tumor necrosis observed 3 to 5 days post-treatment, and no significant early involvement of assessed immune cell populations in tumor cell death[2].
In Vitro, ErSO-TFPy (72 h) potently inhibits viability of ERα-positive human breast cancer cell lines, with IC50 values of ~5-25 nM after 72 h incubation, and has minimal activity against ERα-negative human breast cancer cell lines[2]. ErSO-TFPy (150-450 nM; 6 h) activates the anticipatory unfolded protein response in MCF-7 human breast cancer cells at 150 and 450 nM after 6 h incubation, as measured by increased phosphorylation of EIF2α, increased phosphorylation of AMPK, and cleavage of ATF6[2]. ErSO-TFPy (≥0.01 μM; 72 h) induces potent TRPM4-dependent cell death in MCF-7 human breast cancer cells, with ~80% cell death at concentrations ≥0.01 μM after 72 h incubation, while MCF-7 TRPM4 KO cells show ~1000-fold reduced sensitivity to ErSO-TFPy-induced cell death[2]. ErSO-TFPy (1 μM; 2 h) induces significant TRPM4-dependent cell swelling in MCF-7 Parental human breast cancer cells at 1 μM after 2 h incubation, while MCF-7 TRPM4 KO cells show no measurable cell swelling[2]. ErSO-TFPy (24-120 h) potently inhibits viability of MCF-7, MCF-7Y537S mutant, and MCF-7D538G mutant human breast cancer cells, with single-digit nanomolar IC50 values after 24 and 120 h incubation under both 10% FBS and 10% CD-FBS + 1 nM E2 media conditions[2].
References:
[1]. Marie-Christine Bissery, et al. Abstract 5629_ TEQ103, a novel therapeutic for the treatment of estrogen receptor alpha positive (ERα+) breast cancer. Cancer Res (2025) 85 (8_Supplement_1): 5629.
[2]. Mulligan MP, et al. Single Dose of a Small Molecule Leads to Complete Regressions of Large Breast Tumors in Mice. ACS Cent Sci. 2025;11(2):228-238. Published 2025 Jan 22.
In Vivo, ErSO-TFPy (TEQ103) (1-150 mg/kg total dose; i.v.) exhibits significant, durable antitumor activity in MCF-7 tumor-bearing athymic female mice, with 100% tumor-free survivors achieved regardless of administration schedule[1]. ErSO-TFPy (2-10 mg/kg; i.v.; once weekly; 4 doses) induces complete regression of MCF-7 ERα+ breast cancer xenografts in athymic nude mice at 10 mg/kg, with significant tumor growth inhibition at 5 mg/kg, no significant inhibition at 2 mg/kg, and no significant weight loss[2]. ErSO-TFPy (20 mg/kg; i.v.; once or twice weekly; 4 doses) induces complete regression of Fulvestrant -resistant ST941 ESR1mut breast cancer PDX tumors in athymic nude mice[2]. ErSO-TFPy (2-50 mg/kg; i.v.; single dose) induces near-complete or complete regression of MCF-7 ESR1D538G breast cancer xenografts, including large ~1500 mm3 tumors, in athymic nude mice at 25 mg/kg or 50 mg/kg, with significant inhibition at 5 mg/kg and no significant inhibition at 2 mg/kg[2]. ErSO-TFPy (50 mg/kg; i.v.; single dose) induces significant regression of BT-474 ERα+/HER2+ breast cancer xenografts, including large established tumors, in athymic nude mice[2]. ErSO-TFPy (50 mg/kg; i.v.; single dose) induces rapid necrotic cell death in MCF-7 ESR1D538G breast cancer xenografts, with >90% tumor necrosis observed 3 to 5 days post-treatment, and no significant early involvement of assessed immune cell populations in tumor cell death[2].
In Vitro, ErSO-TFPy (72 h) potently inhibits viability of ERα-positive human breast cancer cell lines, with IC50 values of ~5-25 nM after 72 h incubation, and has minimal activity against ERα-negative human breast cancer cell lines[2]. ErSO-TFPy (150-450 nM; 6 h) activates the anticipatory unfolded protein response in MCF-7 human breast cancer cells at 150 and 450 nM after 6 h incubation, as measured by increased phosphorylation of EIF2α, increased phosphorylation of AMPK, and cleavage of ATF6[2]. ErSO-TFPy (≥0.01 μM; 72 h) induces potent TRPM4-dependent cell death in MCF-7 human breast cancer cells, with ~80% cell death at concentrations ≥0.01 μM after 72 h incubation, while MCF-7 TRPM4 KO cells show ~1000-fold reduced sensitivity to ErSO-TFPy-induced cell death[2]. ErSO-TFPy (1 μM; 2 h) induces significant TRPM4-dependent cell swelling in MCF-7 Parental human breast cancer cells at 1 μM after 2 h incubation, while MCF-7 TRPM4 KO cells show no measurable cell swelling[2]. ErSO-TFPy (24-120 h) potently inhibits viability of MCF-7, MCF-7Y537S mutant, and MCF-7D538G mutant human breast cancer cells, with single-digit nanomolar IC50 values after 24 and 120 h incubation under both 10% FBS and 10% CD-FBS + 1 nM E2 media conditions[2].
References:
[1]. Marie-Christine Bissery, et al. Abstract 5629_ TEQ103, a novel therapeutic for the treatment of estrogen receptor alpha positive (ERα+) breast cancer. Cancer Res (2025) 85 (8_Supplement_1): 5629.
[2]. Mulligan MP, et al. Single Dose of a Small Molecule Leads to Complete Regressions of Large Breast Tumors in Mice. ACS Cent Sci. 2025;11(2):228-238. Published 2025 Jan 22.