ETTAC-2 is a LRG1 PROTAC degrader, degrading LRG1 via the ubiquitin-proteasome pathway with a DC50 value of 8.38 μM. ETTAC-2 penetrates damaged renal cells to reduce the extracellular secretion of LRG1. ETTAC-2 effectively inhibits the TGF-β-Smad3 signaling pathway and diminishes the secretion of fibrosis-associated extracellular matrix proteins. ETTAC-2 degrades LRG1 within fibrotic kidneys and the efficacy in inhibiting the TGF-β-Smad3 pathway both in vitro and vivo. ETTAC-2 can be used for renal fibrosis research [1].
In Vivo, ETTAC-2 (50 mg/kg, i.v., daily for five days) preserves renal tissue structure and function, mitigates renal fibrosis, degrades LRG1 to inhibit the TGF- β-Smad3 pathway with safety profile in unilateral ureteral obstruction mouse model (post-UUO mice)[1].
In Vitro, ETTAC-2 (0-26μM, 1-48 h) induces LRG1 degradation with an DC50 value of 8.38 μM in a time-dependent manner, which degradation can persist for 6 h in HK-2 cells via the ubiquitin-proteasome pathway[1]. ETTAC-2 alleviates cellular fibrosis in vitro by inhibiting the TGF- β-Smad3 pathway in HK-2 cells[1].
References:
[1]. Fan L, et al. Targeted degradation of LRG1 to attenuate renal fibrosis. Asian J Pharm Sci. 2024 Aug;19(4):100941.
In Vivo, ETTAC-2 (50 mg/kg, i.v., daily for five days) preserves renal tissue structure and function, mitigates renal fibrosis, degrades LRG1 to inhibit the TGF- β-Smad3 pathway with safety profile in unilateral ureteral obstruction mouse model (post-UUO mice)[1].
In Vitro, ETTAC-2 (0-26μM, 1-48 h) induces LRG1 degradation with an DC50 value of 8.38 μM in a time-dependent manner, which degradation can persist for 6 h in HK-2 cells via the ubiquitin-proteasome pathway[1]. ETTAC-2 alleviates cellular fibrosis in vitro by inhibiting the TGF- β-Smad3 pathway in HK-2 cells[1].
References:
[1]. Fan L, et al. Targeted degradation of LRG1 to attenuate renal fibrosis. Asian J Pharm Sci. 2024 Aug;19(4):100941.