AUTAC

GPX4-AUTAC is a GPX4-targeting autophagy-mediated degrader designed to selectively induce degradation of GPX4 through autophagy. By promoting the ubiquitination of GPX4 via E3 ligase TRAF6, it enhances the interaction with p62, facilitating the autophagy-dependent degradation process. GPX4-AUTAC has been shown to significantly induce ferroptosis and exhibit notable anti-cancer activity in breast cancer cells, breast cancer-derived organoids, and in the MDA-MB-231 tumor xenograft model. Additionally, it demonstrates potent synergistic effects when used in combination with drugs such as Sulfasalazine or traditional chemotherapy agents like Paclitaxel or Cisplatin.

2-Methylbiphenyl-oxadiazole-NH-Ph-CHO functions as a ligand for PD-L1, playing a crucial role in the development of AUTAC PD-L1 degrader-3. This compound is essential for facilitating targeted degradation of PD-L1, making it a valuable tool in cancer immunotherapy research and studies focusing on the modulation of immune checkpoints. Additionally, it can be utilized in the synthesis of AUTACs for advanced therapeutic applications.

AUTAC2 is an FKBP12-targeting autophagy-mediated degrader designed to promote selective degradation of specific proteins. This compound incorporates a p-Fluorobenzyl Guanine (FBnG) moiety and an SLF ligand, which non-covalently binds to FKBP12. AUTAC2 facilitates the targeted removal of proteins through the autophagy pathway, making it a valuable tool for research applications focused on protein homeostasis and cellular regulation.

AUTAC1 is an autophagy-mediated degrader specifically targeting MetAP2. This compound features a degradation tag and a warhead that ensures target specificity. The structure of AUTAC1 includes p-Fluorobenzyl Guanine (FBnG) and a Fumagillol moiety, with Fumagillol covalently binding to MetAP2. This compound is valuable for research applications focused on the regulation of protein degradation pathways and the study of MetAP2's role in cellular processes.

TSPO ligand-1 is a ligand of AUTAC4, serving as a key component in the synthesis of PROTACs. It interacts with the transmembrane structural domain protein of the mitochondrial outer membrane, facilitating the regulation of mitochondrial autophagy and promoting targeted mitochondrial renewal. Additionally, TSPO ligand-1 is implicated in the transport of cholesterol between mitochondrial membranes and serves as a sensitive biomarker for brain injury and neurodegenerative conditions.

Amino-PEG3-2G degrader-1 is a tag-linker conjugate designed to induce the ubiquitin-proteasome system (UPS) through its PEG linker and pyrazole-linked FBnG tag. This compound facilitates the synthesis of autophagy-targeting chimeras (AUTACs), enabling targeted degradation of specific cellular proteins. Its application is significant in the study of protein homeostasis and cellular degradation pathways, making it a valuable tool for research in cellular biology and therapeutic development.

2G-HaloAUTAC is a second-generation autophagy-targeting chimera designed to enhance the efficacy of AUTACs by substituting the L-Cysteine linker with alternative structures. This compound demonstrates potent degradation activity against EGFP-HaloTag protein via an autophagic mechanism. It serves as a valuable tool for research focused on autophagy and targeted protein degradation, providing insights into cellular protein turnover processes.

FBnG-amino-PEG3-C2-azido is a tag-linker conjugate designed to facilitate targeted protein degradation. It combines the degradation tag FBnG with a glycol linker, Amino-PEG3-C2-azido, to enhance the selective degradation of target proteins. This reagent enables the synthesis of GPX4-AUTAC and is valuable in studies of protein homeostasis and cellular responses to stress. Its versatile application is important for researchers investigating targeted therapeutic strategies in various biological contexts.

AUTAC4 is a mitochondria-targeting autophagy-targeting chimera (AUTAC) designed to downregulate cytosolic proteins while promoting selective mitochondrial degradation through mitophagy. This compound is valuable in studying the mechanisms of mitophagy and its implications in mitochondrial health and disease. It holds potential for applications in research focusing on mitochondrial dysfunction and the role of autophagy in cellular homeostasis.

HaloAUTAC tt15 is an autophagy-targeting chimera (AUTAC) designed to selectively induce the degradation of Halo Tag-conjugated proteins through autophagy. This compound effectively promotes the clearance of unwanted proteins and can be utilized in studies exploring cellular homeostasis, protein turnover, and the roles of autophagy in various diseases. Its ability to target specific proteins makes it a valuable tool for researchers investigating autophagic pathways and protein quality control mechanisms.

FBnG-(Cys-acetamide)-CH2-PEG3-CH2-CH2-CH2-NH2 is a tag-linker conjugate of AUTAC designed to facilitate targeted protein degradation. This compound integrates a p-fluorobenzylguanine (FBnG) tag with a glycol spacer, enabling effective K63-linked polyubiquitination. It demonstrates significant biological activity by promoting the degradation of mitochondrial proteins in HeLa cells, making it a valuable tool for researchers studying mitochondrial dynamics and protein homeostasis.

YT 6-2 is an autophagy-targeting ligand (ATL) that targets p62/SQSTM1, functioning as a control for the AUTAC mechanism. This compound plays a crucial role in enhancing the degradation of the androgen receptor (AR), leading to a reduction in nuclear AR levels and subsequent downregulation of AR target gene expression, including AR-v7. Additionally, YT 6-2 demonstrates efficacy against common AR mutants, making it a valuable tool for research in prostate cancer (PCa) therapies and the study of AR pathway modulation.

Cys-C-cGMP is an autophagy tag designed for AUTACs that facilitates the selective degradation of target proteins through autophagy. It enhances K63-linked ubiquitination of mitochondria in HeLa cells, thereby promoting cellular quality control and elimination of damaged organelles. This compound is valuable for studying autophagy-related pathways and the development of targeted protein degradation strategies.

TSPO ligand-3 serves as a ligand for AUTAC2, which features a p-fluorobenzylguanine (FBnG) moiety alongside a synthetic FKBP ligand (SLF). This compound exhibits notable biological activity by significantly silencing FKBP12 in HeLa cells. Research applications include studying targeted protein degradation and investigating the mechanistic pathways of autophagy-related and intracellular degradation processes.

TSPO ligand-2 is a ligand of AUTAC1, specifically designed to target the MetAP2 enzyme. This compound features a p-fluorobenzylguanine (FBnG) moiety and a Fumagillol component, facilitating the selective degradation of MetAP2 within HeLa cells. It serves as a valuable tool for studying the regulation of protein homeostasis and the therapeutic potential of targeted protein degradation strategies in cellular models.

FBnG is a biochemical reagent that serves as a component of non-ribosomal peptide synthetase/polyketide synthase (NRPS/PKS), playing a critical role in the biosynthesis of fabrubactin (FBN). This compound is instrumental in the synthesis of AUTAC4, specifically within the context of the conjugate FBnG-(Cys-acetamide)-CH2-PEG3-CH2-CH2-CH2-NH2. It is valuable for researchers investigating peptide synthesis and complex molecular structures in drug development and biochemical studies.