Description
LCL-161-phenol is a functionalized IAP ligand for PROTACs.
in vitro
Through derivatization of the SNIPER(AR) molecule at the AR ligand and IAP ligand and linker, this study developed 42a (SNIPER(AR)-51), which shows effective protein knockdown activity against AR. Consistent with the degradation of the AR protein, 42a inhibits AR-mediated gene expression and proliferation of androgen-dependent prostate cancer cells. In addition, 42a efficiently induces caspase activation and apoptosis in prostate cancer cells, which was not observed in the cells treated with AR antagonists._x000D_
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Reference: J Med Chem. 2018 Jan 25;61(2):543-575. https://pubmed.ncbi.nlm.nih.gov/28594553/
in vivo
This study recently developed a protein knockdown system based on hybrid small molecule SNIPERs (Specific and Nongenetic IAP-dependent Protein Erasers) that recruit inhibitor of the apoptosis protein (IAP) ubiquitin ligases to specifically degrade targeted proteins. By incorporating a high affinity IAP ligand, this study developed a novel SNIPER against estrogen receptor α (ERα), SNIPER(ER)-87, that has a potent protein knockdown activity. The SNIPER(ER) reduced ERα levels in tumor xenografts and suppressed the growth of ERα-positive breast tumors in mice._x000D_
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Reference: J Biol Chem. 2017 Mar 17;292(11):4556-4570. https://pubmed.ncbi.nlm.nih.gov/28154167/
target
cIAP1 ligand 1 is the LCL161 derivative based IAP ligand. cIAP1 ligand 1 can be connected to the ABL ligand for protein by a linker to form SNIPER.
