ADAR1i-124 is an A-to-I RNA editing inhibitor by inhibiting the catalytic activities of both ADAR1p150 and ADAR1p110. ADAR1i-124 activates type I interferon ( IFN ) and ZBP1 pathways and dose-dependently inhibits viability across different types of cancer cell lines. ADAR1i-124 can induce cells apoptosis and necroptosis. ADAR1i-124 can be used for the research of cancer, such as cutaneous melanoma and ovarian cancer [1].
In Vitro, ADAR1i-124 (0-200 μM; 2 h) potently inhibits ADAR1p150-mediated A-to-I RNA editing in vitro with IC50 values of 8.8 μM (position 2) and 6.5 μM (position 5)[1]. ADAR1i-124 (300 μM; 2 h) does not inhibit ADAR2-mediated A-to-I RNA editing in vitro[1]. ADAR1i-124 binds selectively to ADAR1p110 with higher affinity than ADAR2 and does not bind to GAPDH[1]. ADAR1i-124 (10 μM; 12 h) induces unedited dsRNA located with MDA5 within the filament structures in mouse Yumm1.7 cutaneous melanoma cells[1]. ADAR1i-124 (10 μM; 12 h) decreases A-to-I editing and prompts the transition of certain dsRNAs from A-form to Z-form in Yumm1.7 cells[1]. ADAR1i-124 (48 h) induces dose-dependent cytotoxicity against mouse (Yumm1.7 CM, HSG2 OC) and human (WM4223 AM, WM3000 CM) cancer cells with IC50 values of 2.3, 1.2, 1.1 and 6.6 μM[1]. ADAR1i-124 (10 μM; 24 h) activates IFN signaling in Yumm1.7 melanoma and HGS2 OC cells[1]. ADAR1i-124 (10 μM; 24 h) induces apoptosis in HeLa and Yumm1.7 cells and also induces necroptosis activated by the ZBP1 pathway in Yumm1.7 cells[1].
References:
[1]. Minakuchi M, et al. Identification of ADAR1i-124: The first effective A-to-I RNA editing inhibitor with promising cancer therapeutic potential. iScience. 2026;29(2):114615. Published 2026 Jan 2.
In Vitro, ADAR1i-124 (0-200 μM; 2 h) potently inhibits ADAR1p150-mediated A-to-I RNA editing in vitro with IC50 values of 8.8 μM (position 2) and 6.5 μM (position 5)[1]. ADAR1i-124 (300 μM; 2 h) does not inhibit ADAR2-mediated A-to-I RNA editing in vitro[1]. ADAR1i-124 binds selectively to ADAR1p110 with higher affinity than ADAR2 and does not bind to GAPDH[1]. ADAR1i-124 (10 μM; 12 h) induces unedited dsRNA located with MDA5 within the filament structures in mouse Yumm1.7 cutaneous melanoma cells[1]. ADAR1i-124 (10 μM; 12 h) decreases A-to-I editing and prompts the transition of certain dsRNAs from A-form to Z-form in Yumm1.7 cells[1]. ADAR1i-124 (48 h) induces dose-dependent cytotoxicity against mouse (Yumm1.7 CM, HSG2 OC) and human (WM4223 AM, WM3000 CM) cancer cells with IC50 values of 2.3, 1.2, 1.1 and 6.6 μM[1]. ADAR1i-124 (10 μM; 24 h) activates IFN signaling in Yumm1.7 melanoma and HGS2 OC cells[1]. ADAR1i-124 (10 μM; 24 h) induces apoptosis in HeLa and Yumm1.7 cells and also induces necroptosis activated by the ZBP1 pathway in Yumm1.7 cells[1].
References:
[1]. Minakuchi M, et al. Identification of ADAR1i-124: The first effective A-to-I RNA editing inhibitor with promising cancer therapeutic potential. iScience. 2026;29(2):114615. Published 2026 Jan 2.