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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.
PROTAC BRD9 Degrader-2 is a bifunctional degrader that targets the BRD9 protein utilizing the PROTAC mechanism. This compound facilitates the targeted ubiquitination and subsequent degradation of BRD9, thus significantly influencing cancer-related pathways. It is instrumental in cancer research, particularly in studies aimed at understanding the role of BRD9 in tumorigenesis and developing potential therapeutic strategies.
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PROTAC SMARCA2 degrader-17 (compound I-290) is a potent PROTAC degrader designed to selectively target and degrade the SMARCA2 protein. It demonstrates effective degradation in A549 cells with a DC50 value of less than 100 nM and achieves a maximum degradation rate exceeding 90% after 24 hours of treatment. This reagent is valuable for research in cancer biology and the investigation of SMARCA2-related pathways.
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PROTAC SMARCA2 degrader-16 (compound I-278) is a PROTAC designed to selectively degrade the SMARCA2 protein. It demonstrates significant biological activity by efficiently reducing SMARCA2 levels in A549 cells, achieving a DC50 value of less than 100 nM and a maximum degradation rate exceeding 90% after 24 hours of treatment. This compound is invaluable for research applications involving the modulation of SMARCA2 in cancer biology and therapeutic development.
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PROTAC SMARCA2 degrader-25 is a potent heterobifunctional molecule that targets SMARCA2 for degradation via the proteasome pathway. With a DC50 value of less than 0.01 μM, this compound efficiently engages the target protein using a specific ligand, a link to facilitate the interaction, and an E3 ligase ligand to promote ubiquitination. Its high efficiency makes it a valuable tool in investigating the role of SMARCA2 in various biological processes and diseases.
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PROTAC SMARCA2/4-degrader-32 is a PROTAC degrader that targets SMARCA2 and SMARCA4 proteins. It demonstrates effective degradation of these proteins in A549 cells, achieving DC50 values below 100 nM and a maximum degradation rate exceeding 90% after 24 hours of treatment. This compound is suitable for research applications focusing on the regulation of chromatin remodeling and its implications in various cancers.
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PROTAC SMARCA2/4-degrader-16 (compound I-337) is a potent PROTAC degrader designed to selectively target and degrade SMARCA2 and SMARCA4 proteins. It demonstrates significant biological activity in A549 cells, achieving DC50 values of less than 100 nM and over 90% maximum degradation rate (Dmax%) after 24 hours of treatment. This compound is valuable for research applications focused on understanding the role of SMARCA2 and SMARCA4 in tumor biology and for exploring targeted protein degradation strategies.
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PROTAC ERα Degrader-8 is a highly potent degrader of estrogen receptor alpha (ERα), demonstrating a DC50 value of 6 nM in MCF7 breast cancer cells. This compound harnesses the proteolysis-targeting chimera (PROTAC) technology to selectively induce the degradation of ERα, facilitating studies on estrogen signaling pathways and potential therapeutic interventions in hormone-driven cancers. Its application in research provides insight into targeting ERα-related pathways for cancer treatment strategies.
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PROTAC SMARCA2 degrader-12 is a molecule specifically designed to induce degradation of the SMARCA2 protein. This PROTAC exhibits potent biological activity, effectively degrading SMARCA2 proteins in A549 cells with a DC50 value of less than 100 nM and achieving over 90% maximum degradation after 24 hours of treatment. This reagent is suitable for research applications focusing on targeted protein degradation and the functional analysis of SMARCA2 in cancer biology.
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PROTAC ERα Degrader-10 (Compound 160a) is a potent degrader targeting estrogen receptor alpha (ERα) with a DC50 of 0.37-1.1 nM in cell lines such as MCF7, T47D, and CAMA-1. This compound effectively induces degradation of ERα, demonstrating significant antitumor activity in mouse models. It is a valuable tool for investigating ERα-related signaling pathways and exploring therapeutic strategies for ERα-positive breast cancers.
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TD-802 is an androgen receptor (AR) PROTAC degrader that demonstrates substantial microsomal stability. It exhibits notable antitumor efficacy in vivo, making it a valuable tool for investigating metastatic castration-resistant prostate cancer. This compound is essential for research aimed at understanding AR modulation and its impacts on cancer progression.
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PROTAC SMARCA2/4-degrader-35 is an efficient degrader targeting the SMARCA2 and SMARCA4 proteins, demonstrating a DC50 of less than 2.5 nM. This compound promotes the ubiquitination and subsequent degradation of the target proteins via the recruitment of E3 ligases. Its potent biological activity makes it valuable for research applications focused on epigenetics and cancer biology, particularly in studies targeting the modulation of chromatin remodeling complexes.
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PROTAC SMARCA2 degrader-14 is a targeted protein degradation compound designed to selectively degrade the SMARCA2 protein. Demonstrating a DC50 value of less than 100 nM, it achieves maximum degradation rates exceeding 90% in A549 cells following a 24-hour treatment. This reagent serves as a valuable tool for research applications focused on elucidating the role of SMARCA2 in various biological processes and therapeutic contexts.
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Chlorohexane-PEG-clozapine is a HaloTag PROTAC degrader that employs clozapine to selectively target and promote the degradation of HaloTag fusion proteins. It effectively reduces luminescence intensity and decreases the protein levels of Halo-Eluc, facilitating the study of target protein dynamics and function. This reagent is valuable for research applications focusing on targeted protein degradation and modulation of protein levels in cellular systems.
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KL-465 is a PROTAC degrader designed to target and degrade MAGE-A3, exhibiting a DC50 of 2 μM in HeLa cells. This compound effectively inhibits the viability of MAGE-A3 positive cancer cell lines, including HCT116, A375, and HeLa, making it a valuable tool for cancer research. Its unique mechanism facilitates targeted protein degradation, offering potential insights into therapeutic interventions for tumors expressing MAGE-A3.
PROTAC SMARCA2/4 degrader-41 is a potent degrader targeting the SMARCA2 and SMARCA4 proteins, exhibiting DC50 and IC50 values both below 0.1 μM. This compound facilitates the selective degradation of these ATP-dependent chromatin remodelers, making it a valuable tool for studying SMARCA2/4-related or SMARCA2/4-deficient cancers. Its application in cancer research can aid in elucidating the role of these proteins in tumorigenesis and therapeutic resistance.
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PROTAC DYRK2 degrader 1 is a selective degrader targeting DYRK2, functioning through the ubiquitin-proteasome system. It exhibits DC50 values of 1.607 μM in MDA-MB-231 cells and 3.265 μM in HeLa cells, effectively inducing DYRK2 degradation. This compound is valuable for research focused on triple-negative breast cancer and cervical cancer, facilitating the exploration of targeted protein degradation mechanisms in these malignancies.
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PROTAC ERα Degrader-7 is a highly effective degradative compound specifically targeting estrogen receptor alpha (ERα). It operates through a PROTAC mechanism and exhibits a DC50 value of 0.000006 µM, demonstrating its potent biological activity. This compound features a cereblon-binding moiety and an ERα-binding ligand, characterized by a benzofused partially saturated six-membered carbocyclic or heterocyclic ring structure. PROTAC ERα Degrader-7 is valuable for research applications focused on hormone signaling and therapeutic strategies in hormone-responsive cancers.
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Folate-MS432 selectively targets MEKs through a PROTAC mechanism, facilitating their degradation in a folate receptor-dependent manner. This compound demonstrates significant efficacy in cancer cells, providing a powerful tool for investigating the role of MEK degradation in tumor biology. Folate-MS432 is valuable for research applications focusing on therapeutic strategies that manipulate signaling pathways in cancer treatment.
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NEP168 is a potent ERα PROTAC degrader that utilizes the GID4 E3 ligase for targeted protein degradation. This compound effectively reduces ERα levels, offering valuable insights into estrogen receptor-related signaling pathways. NEP168 serves as a crucial tool for investigating breast cancer biology and may aid in the development of novel therapeutic strategies.
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PROTAC SMARCA2/4-degrader-7 is a selective protein degrader that targets SMARCA2 and SMARCA4 proteins. Demonstrating effective degradation in A549 cells, it achieves DC50 values of less than 100 nM and results in more than 90% degradation after 24 hours of treatment. This compound serves as a valuable tool for investigating the roles of SMARCA2 and SMARCA4 in cancer biology and other research applications involving epigenetic regulation.
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PROTAC SMARCA2/4-degrader-22 is a targeted protein degradation reagent designed to selectively degrade SMARCA2 and SMARCA4 proteins. This compound effectively reduces SMARCA2 and SMARCA4 levels in A549 cells, achieving DC50 values of less than 100 nM and exceeding 90% maximum degradation rate after 24 hours of treatment. It is a valuable tool for research into the role of these proteins in various biological processes and disease states.
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Arg-TERRα is a mini-PROTAC designed to target estrogen-related receptor alpha (ERRα). This compound facilitates the degradation of ERRα via the N-end rule pathway, effectively suppressing the proliferation and migration of MCF7 breast cancer cells. Arg-TERRα serves as a valuable tool for investigating the role of ERRα in breast cancer research and therapeutic development.
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PROTAC BRD9 Degrader-3 is a bifunctional degrader targeting BRD9 through the PROTAC mechanism, facilitating targeted protein degradation. This compound exhibits potent biological activity by selectively degrading BRD9, which plays a critical role in various cancer pathways. It is intended for use in cancer research to elucidate the functional significance of BRD9 and to explore novel therapeutic strategies in oncology.
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ITK Degrader 2 is a PROTAC-based compound that specifically targets and degrades the interleukin-2-inducible T-cell kinase (ITK) with a DC50 value of less than 10 nM. In pharmacokinetic studies in mice, this orally active degrader demonstrates a maximum concentration (Cmax) of 0.87 μM and achieves peak plasma levels (Tmax) at 2 hours post-administration. At a dosage of 90 mg/kg, ITK Degrader 2 effectively reduces ITK levels by 20% within 6 hours, making it a valuable tool for exploring ITK-related signaling pathways and their implications in immune responses.
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PROTAC BRD9 Degrader-8 is a selective BRD9 PROTAC degrader that operates through targeted protein degradation, exhibiting a DC50 of 16 pM. This compound effectively induces cell cycle arrest in the G1 phase and promotes apoptosis, making it a valuable tool for studies focused on acute myeloid leukemia and diffuse large B-cell lymphoma. Its mechanism provides a unique approach to modulating BRD9 levels in therapeutic research.
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