F-box and WD repeat domain containing 11 (FBXW11)

F-box and WD repeat domain containing 11 (FBXW11), also known as beta-transducin repeat-containing protein 2 (βTrCP2), is an F-box protein that serves as a substrate recognition component in the SCF E3 ubiquitin ligase complex[4][7]. FBXW11 specifically binds phosphorylated substrates and targets them for ubiquitin-mediated proteasomal degradation. It plays essential roles in the regulation of the cell cycle, cell differentiation, apoptosis, and various signaling pathways, including the WNT/β-catenin and NF-κB pathways[3][5]. Overexpression or dysregulation of FBXW11 has been implicated in the progression and metastasis of multiple cancer types such as colorectal, skin, breast, and pancreatic cancers, and it is considered oncogenic in various contexts[3][4][5]. While research is ongoing to develop FBXW11-targeted therapeutics, no clinically approved drugs directly targeting this protein are known. The protein has three isoforms, with a molecular weight around 61 kDa[5]. Concerns about its therapeutic targeting relate to its broad physiological importance and possible functional overlap with its paralog FBXW1 (β-TrCP1)[4][5].

Other names

BTRCP2FBW1BFBXW1BKIAA0696HOSFbw1bBTRC2Fbw11beta-transducin repeat-containing protein 2F-box/WD repeat-containing protein 1BHomologous to Slimb protein

Drugs or molecules targeting FBXW11 would likely function via inhibition of E3 ubiquitin ligase activity (prevention of substrate ubiquitination), modulation of protein degradation pathways, or pathway-specific disruption of SCF complex–mediated substrate recognition[3][4].