FRAT1 Inibidores

Os inibidores comuns de FRAT1 incluem, entre outros, Galeterone CAS 851983-85-2, XAV939 CAS 284028-89-3, Wnt-C59 CAS 1243243-89-1, JW 55 CAS 664993-53-7 e o inibidor de β-Catenina/Tcf, FH535 CAS 108409-83-2.

FRAT1 inhibitors encompass a diverse group of chemicals that indirectly regulate the activity of the FRAT1 protein, targeting various components of the Wnt/β-catenin signaling pathway. This pathway is a complex cellular communication system that is fundamental in regulating cell fate, proliferation and migration. The relevance of these inhibitors stems from their ability to modulate the Wnt pathway, which FRAT1 is known to promote by acting as a positive regulator. By inhibiting certain aspects of the Wnt/β-catenin signaling cascade, these compounds can reduce the functional production of FRAT1.

The class of FRAT1 inhibitors includes small molecules that can disrupt the post-translational modification of Wnt fixers, such as C59 and LGK-974, which inhibit the Porcupine enzyme, or disrupt the nuclear actions of β-catenin, which is the central mediator of Wnt signaling transduction. Compounds such as ICG-001 and PNU-74654 achieve this by inhibiting the interaction between β-catenin and its co-factors, such as the CREB protein-binding protein and the TCF/LEF (T-cell factor/lymphoid enhancer-binding factor) family of transcription factors, respectively. This prevents the transcription of Wnt target genes, which are crucial for exerting the effects of the pathway. Other inhibitors, such as XAV-939 and JW55, target the enzyme tankyrase, which facilitates the poly-ADP-ribosylation and subsequent proteasomal degradation of Axin, a negative regulator of the Wnt pathway. By stabilizing Axin, these inhibitors promote the degradation of β-catenin, reducing its cytoplasmic levels and, consequently, its nuclear signalling capabilities.