AUTACs

TSPO ligand-2 (Carbonic acid) is a ligand of AUTAC1 which contains a p-fluorobenzylguanine and a Fumagillol moiety.

AUTAC1 is a MetAP2-targeted autophagy-mediated degrader (AUTAC) with potential anticancer activity that degrades MetAP2 and FKBP12 proteins and can be used to synthesize PROTAC.

YTK-105 is a ligand targeting autophagy that binds to p62.

YT 6-2 is an autophagy-targeting ligand (ATL) aimed at p62/SQSTM1, used in the synthesis of AUTOTAC degrader ATC-324. ATC-324 induces the formation of AR/p62 complexes, leading to the autophagic-lysosomal degradation of AR. It reduces nuclear AR levels, downregulates the expression of AR and AR-v7 target genes, and also degrades common AR mutants in PCa.

Halo PROTAC 1 is a PROTAC, which is a ligand having activity to bind to an intracellular proteins fused with HaloTag and a structure having activity to induce autophagy of an intracellular molecule are linked via a PEG linker[1].

Cys-C-cGMP serves as an autophagy tag for AUTACs (autophagy-targeting chimeras). It enhances K63-linked ubiquitination of mitochondria within HeLa cells [1].

PBA-1105 TFA is an autophagy-targeting chimera (AUTOTAC) that induces p62 self-oligomerization. This compound selectively binds to the exposed hydrophobic regions of misfolded proteins, promoting their degradation through the autophagy (autophagy) pathway. Additionally, PBA-1105 TFA enhances the autophagic flux of Ub-bound aggregates.

YOK-1304, an autophagy-targeting chimera (AUTOTAC), induces self-oligomerization of p62.

JAK1-IN-16 (compound 4l) acts as an inhibitor of JAK1/STAT3 and effectively downregulates the expression of TLR4 protein.

PD-L1degrader-2 (Compound B3) is an orally effective AUTAC degrader that degrades PD-L1 via the autophagy-lysosome pathway with a DC50 of 0.5 μM. It inhibits the interaction between PD-1 and PD-L1, with an IC50 of 22.8 nM. PD-L1degrader-2 upregulates the expression of Atg9b, Lamp1, and Mitf, activating the autophagy-lysosome system. It exhibits antitumor activity in the CT26 mouse model.

YT-8-8 is a ligand for the p62-ZZ domain and can activate p62-dependent selective autophagy. This compound is also applicable in AUTOTAC design.

Anle138b-F105 is an autophagy-targeting chimera (AUTOTAC) with a DC50 value of 3 nM. It targets tauP301L for lysosomal degradation.

Fumagilin-105, an autophagy-targeting chimera (AUTOTAC), induces self-oligomerization of p62 and exhibits a DC50 of 0.7 μM against MetAP2 in HEK293 cells.

AUTAC2, an autophagy-mediated degrader (AUTAC) targeting FKBP12, comprises an FBnG (p-Fluorobenzyl Guanine) and an SLF (c ligand of FKBP) moiety. The SLF component binds non-covalently to FKBP12 [1].

TSPO Ligand-Linker Conjugates 1, comprising a translocator protein (TSPO) ligand and a linker, is instrumental in synthesizing mitochondria-targeting autophagy-targeting chimera (AUTAC). This compound binds TSPO on the outer mitochondrial membrane (OMM), facilitating the degradation of malfunctioning mitochondria and proteins through mitophagy, thereby enhancing mitochondrial function. It holds potential applications in research related to mitochondrial dysfunction, encompassing neurodegenerative diseases, cancer, and diabetes [1].

FBnG-(Cys-acetamide)-CH2-PEG3-CH2-CH2-CH2-NH2 serves as a linker for AUTAC4, a compound comprising a p-fluorobenzylguanine (FBnG) unit and a phenylindole moiety, capable of inducing K63-linked polyubiquitination and subsequent degradation of mitochondria within HeLa cells [1].

BRD4 degrader-5 (Compound 23) is a protein degrader utilizing a hydrophobic tag (HyTag) that targets BRD4 for degradation through endoplasmic reticulum stress and the autophagy-lysosome pathway (DC50 = 24.7 μM). It also inhibits the proliferation of 4T1 cancer cells, with an IC50 of 20.6 μM.

YT 6-2 analog-1 (compound 2-3) serves as an autophagy-targeting ligand (ATL) aimed at p62/SQSTM1, useful in synthesizing the AUTOTAC degrader ATC-324 for the Androgen Receptor (AR). ATC-324 promotes the formation of AR/p62 complexes, leading to the autophagic-lysosomal degradation of AR. It effectively reduces nuclear AR levels, downregulates the expression of AR and AR-v7 target genes, and can degrade common AR mutants found in prostate cancer (PCa).

PBA-1105b, a longer PEGylated derivative of PBA-1105, is an autophagy-targeting chimeric compound (AUTOTAC) that can induce self-oligomerization of p62. It enhances the autophagic flux of Ub-bound aggregates.

YOK-2204 is a ligand for the p62-ZZ domain and activates p62-dependent selective autophagy. It is also applicable in the design of AUTOTACs.

PHTPP-1304, a chimeric autophagy-targeting compound (AUTOTAC) based on PHTPP, induces p62 self-oligomerization and degrades estrogen receptor ERβ (DC50: ~2 nM, HEK293T). Additionally, PHTPP-1304 facilitates the formation of p62+ERβ+ puncta in a dose-dependent manner, influencing autophagic flux.

PBA-1105, an autophagy-targeting chimeric molecule (AUTOTAC), facilitates the self-oligomerization of p62. Additionally, PBA-1105 enhances the autophagic flux of Ub-conjugated aggregates.

VinclozolinM2-2204 is an androgen receptor AUTOTAC degrader with a DC50 of 200 nM in LNCaP prostate cancer cells. It induces the formation of AR+LC3+ autophagic membranes and is applicable for cancer research.

YT 6-2-PEG3-C2-NH2 is a conjugate of the autophagy-targeting ligand (ATL) targeting p62/SQSTM1 and an AUTOTAC linker. It is used in the synthesis of the AUTOTAC degrader ATC-324 for the androgen receptor (AR). ATC-324 induces the formation of the AR/p62 complex, leading to autophagy-lysosomal degradation of AR. This action reduces nuclear AR levels and downregulates target gene expression of AR and AR-v7, effectively degrading common AR mutants found in prostate cancer (PCa).