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AUTACs

Autophagy-targeting chimeras (AUTACs) contain a guanine tag and a specific binder of an intracellular target of interest. AUTACs both downregulated cytosolic proteins and promoted targeted mitochondrial turnover via mitophagy. Mitochondria-targeted AUTAC (mito-AUTAC) treatment significantly improved mitochondrial activities in Down syndrome (DS)-derived fibroblast cells. This AUTAC technology may hold promise as the first autophagy-inducing agent with cargo specificity.

TSPO ligand-2 
T600151160640-95-8
TSPO ligand-2 (Carbonic acid) is a ligand of AUTAC1 which contains a p-fluorobenzylguanine and a Fumagillol moiety.
  • $58
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AUTAC1
T740252241669-09-8
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.
  • $399
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YTK-105
T87944774192-20-0
YTK-105 is a ligand targeting autophagy that binds to p62.
  • $30
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Cys-C-cGMP
T826322241669-85-0
Cys-C-cGMP serves as an autophagy tag for AUTACs (autophagy-targeting chimeras). It enhances K63-linked ubiquitination of mitochondria within HeLa cells [1].
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YT 6-2
T2030192409959-90-4
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.
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Halo PROTAC 1
T179952241668-45-9
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].
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PDL1 degrader-2
T201649
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.
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PBA-1105 TFA
T205092
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.
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YOK-1304
T885692409960-03-6
YOK-1304, an autophagy-targeting chimera (AUTOTAC), induces self-oligomerization of p62.
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10-14 weeks
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FBnG-(Cys-acetamide)-CH2-PEG3-CH2-CH2-CH2-NH2
T824132241669-84-9
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].
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AUTAC2
T740262241669-08-7
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].
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TSPO Ligand-Linker Conjugates 1
T74571
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].
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Fumagilin-105
T887252410081-58-0
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.
  • $3,320
3-6 months
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YT-8-8
T88781892572-23-5
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.
  • $1,620
4-6 weeks
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Anle138b-F105
T887312941386-44-1
Anle138b-F105 is an autophagy-targeting chimera (AUTOTAC) with a DC50 value of 3 nM. It targets tauP301L for lysosomal degradation.
  • $1,970
10-14 weeks
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YT 6-2 analog-1
T2032342409960-12-7
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).
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YOK-2204
T885012409959-99-3
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.
  • $1,520
6-8 weeks
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PBA-1105
T886812410081-56-8
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.
  • $1,520
4-6 weeks
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PBA-1105b
T887622941386-60-1
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.
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PHTPP-1304
T887932410081-60-4
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.
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TSPO ligand-3
T809282241669-89-4
TSPO ligand-3, functioning as an AUTAC2 ligand, incorporates both a p-fluorobenzylguanine (FBnG) and a synthetic ligand of FKBP (SLF) moiety, leading to the substantial inhibition of FKBP12 in HeLa cells [1].
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YT 6-2-PEG3-C2-NH2
T203134
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).
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