Title : Discovery of a potent SCAP degrader that ameliorates HFD-induced obesity, hyperlipidemia and insulin resistance via an autophagy-independent lysosomal pathway.

Pub. Date : 2021 Jul

PMID : 32432943






6 Functional Relationships(s)
Download
Sentence
Compound Name
Protein Name
Organism
1 However, the current known SCAP inhibitors, such as oxysterols, induce endoplasmic reticulum (ER) stress and NR1H3/LXRalpha (nuclear receptor subfamily 1 group H member 3)-SREBF1/SREBP-1 c-mediated hepatic steatosis, which severely limited the clinical application of this inhibitor. Oxysterols SREBF chaperone Mus musculus
2 In this study, we identified a small molecule, lycorine, which binds to SCAP, which suppressed the SREBF pathway without inducing ER stress or activating NR1H3. lycorine SREBF chaperone Mus musculus
3 Mechanistically, lycorine promotes SCAP lysosomal degradation in a macroautophagy/autophagy-independent pathway, a mechanism completely distinct from current SCAP inhibitors. lycorine SREBF chaperone Mus musculus
4 Mechanistically, lycorine promotes SCAP lysosomal degradation in a macroautophagy/autophagy-independent pathway, a mechanism completely distinct from current SCAP inhibitors. lycorine SREBF chaperone Mus musculus
5 The interaction of SCAP and SQSTM1 requires the WD40 domain of SCAP and the TB domain of SQSTM1. Terbium SREBF chaperone Mus musculus
6 Interestingly, lycorine triggers the lysosome translocation of SCAP independent of autophagy. lycorine SREBF chaperone Mus musculus