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PROTAC degraders recruit an E3 ubiquitin ligase to a target protein so that the proteasome degrades it. Each proteolysis-targeting chimera (PROTAC) links a target-binding ligand to an E3 ligase ligand through a chemical linker. The approach was first described in 2001, and later work showed that small-molecule PROTACs can act catalytically, removing several target copies per molecule. Examples include the bromodomain and extra-terminal (BET) degraders dBET1, MZ1 and ARV-771, and the estrogen receptor degrader ERD-308. Degraders of anti-apoptotic proteins, such as PROTAC Mcl1 degrader-1, are also listed.
dBAZ2B is a selective BAZ2B PROTAC degrader with a DC50 of 19 nM. This compound effectively promotes the degradation of the BAZ2B protein, facilitating investigations into protein homeostasis and targeted protein degradation mechanisms. It serves as a valuable tool for research in cellular signaling pathways and potential therapeutic applications in cancer and other diseases.
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LGF308 is a selective PROTAC degrader targeting BRD4, designed to promote the degradation of BRD4 through the formation of a ternary complex with DCAF11. This compound demonstrates potent cytotoxicity in cancer cells while sparing normal cells, effectively inducing apoptosis by upregulating apoptosis-related proteins. Additionally, LGF308 significantly inhibits tumor cell proliferation and migration in breast cancer and triple-negative breast cancer cell lines, making it a valuable tool for research in breast cancer biology.
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PROTAC SMARCA2 degrader-31 is a targeted degrader of the SMARCA2 protein, utilizing a proteolysis-targeting chimera (PROTAC) approach. This compound has demonstrated an impressive degradation rate of up to 99% in H929 cells at a concentration of 100 nM. It exhibits significant anti-proliferative activity, making it a valuable tool for cancer research and investigations into SMARCA2-related pathways.
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JP-2-249 is a selective SMARCA2 degrader that functions as a molecular glue. It has been demonstrated to significantly reduce SMARCA2 protein levels in MV-4-11 cells at concentrations ranging from 1 to 10 μM. This compound is valuable for research applications focused on the modulation of cancer-related pathways involving SMARCA2.
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PROTAC SMARCA2 degrader-7 (Compound I-428) selectively targets and degrades the SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A, specifically SMARCA2. It has demonstrated effective degradation of both SMARCA2 and SMARCA4 in the MV411 cell line, with DC50 values of less than 100 nM and between 100-500 nM, respectively. This compound serves as a valuable tool for studying chromatin remodeling and its implications in cancer biology and therapeutic development.
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PROTAC SMARCA2 degrader-18 is a synthetic molecule designed to selectively target and degrade the SMARCA2 protein. This compound exhibits promising activity in modulating SMARCA2 levels and has potential applications in the study of non-small cell lung cancer (NSCLC). Researchers can utilize PROTAC SMARCA2 degrader-18 to investigate the implications of SMARCA2 degradation in cancer biology and therapeutic development.
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TrimTAC1 is a TRIM21-based PROTAC designed to target BRD4 for selective degradation. This compound effectively promotes the degradation of NUP98FG-mEGFP-BRD4BD2 nuclear condensates without affecting soluble mEGFP-BRD4BD2 in A549 cells. TrimTAC1 is valuable for research applications aimed at studying the dynamics of protein degradation and the role of BRD4 in various cellular processes.
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PROTAC SMARCA2/4-degrader-20 is a novel PROTAC degrader targeting the catalytic subunits of the SWI/SNF complex, specifically SMARCA2 and SMARCA4. This compound effectively induces degradation of SMARCA2 in A549 and MV411 cell lines with a DC50 of less than 100 nM, while degrading SMARCA4 in MV411 cells with a DC50 range of 100-500 nM. It serves as a valuable tool for studying the functional roles of SWI/SNF complex components in various biological processes and disease states.
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PROTAC BET Degrader-16 is a potent BET PROTAC degrader specifically targeting BRD4 with a DC50 of 0.31 nM, displaying a strong selectivity for BRD4 over other BET family proteins. This compound facilitates the degradation of BRD2, BRD3, and BRD4 through the ubiquitin-proteasome system, utilizing CRBN E3 ligase recruitment. Research applications include the induction of cell cycle arrest and promotion of apoptosis, demonstrating anti-tumor effects particularly in acute myeloid leukemia.
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JV8 is a potent BRD4 PROTAC degrader that facilitates the ubiquitination and subsequent degradation of the BRD4 protein, leading to induced apoptosis. This compound exhibits significant antitumor activity, demonstrated in a 4T1 orthotopic tumor model in mice. JV8 serves as a valuable tool for research in cancer therapeutics and the study of protein degradation pathways.
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PROTAC SMARCA2/4-degrader-15 is a potent PROTAC degrader targeting the catalytic subunits SMARCA2 and SMARCA4 of the SWI/SNF complex. It demonstrates efficient degradation of SMARCA2 in A549 cells and SMARCA4 in MV411 cells, with DC50 values below 100 nM. This compound is valuable for researchers investigating the role of these proteins in epigenetic regulation and cancer biology.
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PROTAC SMARCA2/4-degrader-9 is a targeted protein degrader that specifically targets the catalytic subunits of the SWI/SNF complexes, SMARCA2 and SMARCA4. This compound effectively degrades SMARCA2 in MV411 and A549 cell lines with a DC50 value of less than 100 nM, while also demonstrating similar potency against SMARCA4 in MV411 cells. PROTAC SMARCA2/4-degrader-9 serves as a valuable tool for studying the biological functions of these proteins and their roles in cancer research and therapeutic development.
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PROTAC SMARCA2 Degrader-23 is a potent and selective degrader targeting the SMARCA2 protein. With a DC50 of less than 100 nM, it effectively induces degradation of SMARCA2. This compound is primarily utilized in cancer research, facilitating studies on the therapeutic potential of targeting SMARCA2 for oncological applications.
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PROTAC BRD4 Degrader-14 is a targeted protein degradation compound designed to bind both von Hippel-Lindau (VHL) and the BRD4 protein. It demonstrates potent activity with IC50 values of 1.8 nM for BRD4 BD1 and 1.7 nM for BRD4 BD2. This reagent effectively induces degradation of BRD4 in PC3 prostate cancer cells, making it a valuable tool for studying BRD4-related pathways and potential therapeutic interventions in cancer research.
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PROTAC SMARCA2 degrader-3 is a PROTAC degrader specifically targeting the SWI/SNF ATPase subunit SMARCA2. This compound induces proteasomal degradation of SMARCA2, demonstrating significant anticancer activity. It is valuable for research applications focused on cancer biology and the exploration of therapeutic strategies targeting chromatin remodeling complexes.
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PROTAC BRD4 Degrader-15 is a proteolysis-targeting chimera (PROTAC) that utilizes ligands for von Hippel-Lindau (VHL) and BRD4, exhibiting IC50 values of 7.2 nM for the BRD4 BD1 domain and 8.1 nM for the BD2 domain. This compound effectively induces the degradation of the BRD4 protein in PC3 prostate cancer cells. Its ability to selectively target and eliminate BRD4 makes it a valuable tool for research in cancer biology and therapeutic applications aimed at modulating gene expression.
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PROTAC SMARCA2/4-degrader-28 is a PROTAC (Proteolysis Targeting Chimeras) designed to target and degrade SMARCA2 and SMARCA4 proteins. This compound utilizes a combination of a CRL2VHL ligand, a linker, and a SMARCA-BD ligand to facilitate targeted degradation, thus modulating the expression of these critical chromatin remodeling factors. Its primary applications include studying the functional roles of SMARCA2 and SMARCA4 in cancer biology and epigenetic regulation, making it a valuable tool for researchers investigating therapeutic strategies in oncology and related fields.
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PROTAC BRM/BRG1 Degrader-1 is a targeted protein degradation agent designed to selectively degrade the BRM and BRG1 proteins, with a DC50 of 10-100 nM for BRM and greater than 1 μM for BRG1. This compound facilitates the study of chromatin remodeling complexes in cancer research, enabling the investigation of their roles in tumorigenesis and potential therapeutic strategies. The molecule is composed of an E3 ligase ligand, a linker, and a selective BRM/BRG1 inhibitor, allowing for precise modulation of protein levels in cellular systems.
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(S)-GNE-987 is a selective PROTAC BRD4 degrader that functions by abrogating binding to von Hippel-Lindau while maintaining specific interactions with BRD4 bromodomains. With IC50 values of 4 nM for BD1 and 3.9 nM for BD2, (S)-GNE-987 facilitates targeted degradation of BRD4, making it a valuable tool in research focused on epigenetic regulation and cancer therapy. Additionally, it can be instrumental in the design of PROTAC-Antibody Conjugates (PAC) for enhanced therapeutic applications.
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PROTAC BRM degrader-1 is a PROTAC-based compound that selectively targets and degrades the BRM and BRG1 proteins, demonstrating DC50 values of 93 pM and 4.9 nM, respectively. This compound facilitates the targeted protein degradation pathway, making it a valuable tool in research aimed at understanding complex biological processes involving these ATP-dependent chromatin remodeling factors. Its application in cellular and molecular biology studies could provide insights into the roles of BRM and BRG1 in various diseases, including cancer.
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PROTAC SMARCA2/4-degrader-4 (Compound I-434) is a targeted PROTAC degrader that specifically promotes the degradation of the catalytic subunits SMARCA2 and SMARCA4 of the SWI/SNF complex. It demonstrates robust biological activity, achieving degradation of SMARCA2 and SMARCA4 in MV411 and A549 cell lines with DC50 values below 100 nM. This compound is valuable for research applications focused on the modulation of chromatin remodeling processes and the elucidation of the roles of SMARCA proteins in cancer biology.
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dBRD9 dihydrochloride is a selective degrader of BRD9, targeting the protein for degradation through the PROTAC mechanism. This compound demonstrates efficacy in inhibiting the proliferation of acute myeloid leukemia (AML) cell lines, making it a valuable tool for research in cancer biology and therapeutic development. Its utility in studying BRD9's role in oncogenic processes positions dBRD9 dihydrochloride as a significant reagent for investigators exploring targeted protein degradation strategies.
PROTAC SMARCA2/4-degrader-27 is a PROTAC-based degrader that specifically targets the SMARCA2 and SMARCA4 proteins. This compound induces targeted protein degradation, facilitating the selective modulation of these chromatin remodelers. It is essential for research applications exploring the roles of SMARCA2 and SMARCA4 in cancer and other diseases, allowing for valuable insights into epigenetic regulation and therapeutic strategies.
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PROTAC SMARCA2 degrader-30 is an investigative PROTAC designed for targeted degradation of SMARCA2 protein. It demonstrates potent biological activity with a DC50 of less than 100 nM in H1299 cells, making it a valuable tool for research in cancer biology and therapeutic development. This compound may facilitate studies on the role of SMARCA2 in cellular processes and its potential as a therapeutic target in oncogenic pathways.
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PROTAC BRD4 Degrader-3 is a targeted protein degradation compound that operates through the recruitment of von Hippel-Lindau (VHL) ligands to promote the ubiquitination and subsequent proteasomal degradation of the BRD4 protein. This compound demonstrates significant efficacy in downregulating BRD4, a key regulator in various cancers and inflammatory diseases. Research applications for PROTAC BRD4 Degrader-3 include the investigation of therapeutic strategies for cancer treatment and exploring the role of BRD4 in gene expression and signaling pathways.
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