Fkbp12 protac. Inhibition of FKBP12 activity by biochemical molecules, such as specific antibodies, and novel proteolysis targeting chimera (Protein Degraders), will be a valuable approach for disease therapy. dTAG Degraders are Dec 1, 2024 · Advances in designing ternary complexes: Integrating in-silico and biochemical methods for PROTAC optimisation in target protein degradation FKBP12 PROTAC dTAG-7 is a bifunctional PROTAC® degrader inducing the selective degradation of FKBP12F36V fusion proteins and BET BRD4, consisting of a ligand selective for F36V single-point mutated FKBP12 conjugated to a cereblon ligand by a linker. Derivatives of FKBP12 binding molecules that lack immunosuppression activity were developed and their capacity in hepcidin regulation should also be tested in the future. It functions by harnessing the ubiquitin-proteasome system through the formation of a ternary complex between FKBP12, a ligand for the E3 ubiquitin ligase, and the proteasome. Pink: FKBP12 ligand (HY-170988); Black: linker (HY-W004640); Blue: E3 ligase ligand. PROTACs (Proteolysis targeting chimeras) are heterobifunctional nanomolecules that structurally comprised of two functional motifs linked by a linker. Washing of cells to remove free heterobifunctional compound did not affect the durability of KB02-SLF-mediated degradation of FKBP12_NLS evaluated ~24 h post-washout, but led to full recovery of FKBP12_NLS in cells treated with the non-covalent PROTAC lenalidomide-SLF (Fig. Aug 30, 2025 · FKBP12 PROTAC dTAG-48 (Dana-Farber Cancer Institute): a FKBP1A degraders Drug, Initially developed by Dana-Farber Cancer Institute, Inc. The TAG Degradation Platform enables the knockdown of your protein of interest (POI) by adding a tag (or degron tag), via genetic modification, which can then be targeted by a small molecule Degrader. A flexible linker, 2xGSSG is present between each component. Jan 27, 2025 · This study reported a CRISPR transcriptional activation screen that identified FBXO22, which, upon induced expression, enhances the activity of a hypoactive electrophilic PROTAC degrader of FKBP12. 2025 Apr 17. Store at Store at -20°C. The ER FKBPs: FKBP13, 19, 22, 23, 60 and 65 all contain an N-terminal ER signal peptide. Mar 27, 2024 · It is worth noting that FKBP12 F36V fusion protein has been widely used as a tool in PROTAC studies (46), cell imaging (47), etc. We also provide services including custom synthesis, process optimization, commercial production, peptide custom services, ADC one-stop service, etc. Additionally, it can improve the durability of protein degradation in biological systems. 22-SLF degrades other endogenous proteins, such as BRD4 and EML4-ALK fusion protein. To validate this method, the dTAG system has also been applied to protein chimeras of FKBP12 F36V fused with EZH2, HDAC1, KRAS, MYC and PLK1. Jan 15, 2024 · Here, we report the discovery of the first FKBP51 proteolysis targeting chimera (PROTAC) that enables degradation of FKBP51 abolishing its scaffolding function. Most of the PROTAC candidates that have been Novel PROTAC to target FKBP12: the potential to enhance bone morphogenetic protein activity and apoptosis in multiple myeloma (1R)-3- (3,4-dimethoxyphenyl)-1- (2- ( ( (3- (2- (2- (3- (2- ( (2- (2,6-dioxopiperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl)oxy)acetamido)propoxy)ethoxy Sep 1, 2024 · To explore this, we synthesized a PROTAC, 2G07-SLF, by conjugating 2G07 to a widely used FKBP12 ligand33via a PEG linker (Fig. RC32 combines two key components: Rapamycin (HY-10219), which serves as the ligand for FKBP12, and Pomalidomide (HY-10984), which acts as the ligand for an E3 ubiquitin ligase. FKBP12 PROTAC dTAG-13 (dTAG-13) is a degrader of FKBP12F36V with expression of FKBP12F36V in-frame with a protein of interest. Our results revealed that PROTAC-mediated FKBP12 degradation is an ideal strategy to upregulate hepcidin expression without immunosuppression activity. FKBP12 PROTAC dTAG-13 (dTAG-13) also is a specific degrader of BET bromodomain transcriptional co-activator BRD4 by bridging BET bromodomains to an E3 FKBP12 PROTAC dTAG-13 (dTAG-13) is a PROTAC-based heterobifunctional degrader. More than a dozen companies have brought PROTAC molecules into clinical trials En route to the development of a PROTAC candidate library targeting the prolyl isomerase FKBP12, we serendipitously discovered a set of small molecule precursors with unexpected degradation activity. Moiety in red, linker; moiety in blue, rapamycin; moiety in green, pomalimide. The dTAG system pairs a novel degrader of FKBP12 F36V with expression of FKBP12 F36V in-frame with a protein of interest. demonstrate proof-of-concept of truly disease-specific TPD by redirecting virally encoded E3 ubiquitin ligases with VIPER-TACs in a chemical biology model system. Jun 26, 2024 · SP3N-induced FKBP12 degradation depends on the primary amine and is UPS dependent En route to the development of a PROTAC candidate library targeting the prolyl isomerase FKBP12, we FKBP12 PROTAC dTAG-7 (dTAG-7) is a heterobifunctional degrader. Nov 9, 2023 · Unsere Ergebnisse zeigen, wie (nicht-kognate) PROTAC-Protein Kontakte eine starke unerwünschte Abbaupräferenz zwischen engen Homologen überwinden können (z. FKBP12 PROTAC dTAG-7 (dTAG-7) is a heterobifunctional degrader. 35 μM and a Dmax of 89%. Mar 26, 2018 · The dTAG system pairs potent heterobifunctional degraders and extensible tagging strategies to achieve immediate and reversible degradation of divergent proteins, facilitating biological Feb 5, 2019 · a Mechanism of action of PROTAC. FKBP12 PROTAC dTAG-7 (Cat. Peptidyl-prolyl cis-trans isomerase FKBP1A is an enzyme that in humans is encoded by the FKBP1A gene. 1038/s41392-022-00970-8. FKBP12 PROTAC FM4 is a PROTAC degrader of MTH1, with a Dmax ＞90%. FKBP36, 38, 51 and 52 contain multiple TPR domains. A typical PROTAC degrader consists of three components: a small molecule that binds to a target protein, Besides inhibition, RAS degradation offers another alternative approach at inhibiting RAS function to target RAS-dependent cancer cells. , Now, its global highest R&D status is Preclinical, Mechanism: FKBP1A degraders(FK506-binding protein 1A degraders), Therapeutic Areas: Neoplasms,Hemic and Lymphatic Diseases, Active Indication: Leukemia, Active Org. FKBP12 PROTAC dTAG-13 (dTAG-13) is an in vivo-active heterobifunctional adation tag (dTAG) small molecule that engage FKBP12F36V and CRBN, selectively degrade FKBP12F36V in a CRBN-dependent manner in cells. FKBP12 PROTAC dTAG-7 contains a ligand that selects for F36V, a PEG linker, and a cereblon ligand. Together, these studies implicate FBXO22 as a ‘hijackable’ E3 ubiquitin ligase suitable for FKBP12 PROTAC dTAG-7; CAS Number: 2064175-32-0; Linear Formula: C63H79N5O19; find AChemBlock-ADVH9A987E6C MSDS, related peer-reviewed papers, technical documents, similar products & more at Sigma-Aldrich 22-SLF is a PROTAC degrader, that degrades FK506-binding protein 12 (FKBP12) with a DC50 of 0. Oct 20, 2022 · Differentially localized Halo or FKBP12 F36V proteins displayed varying levels of degradation using the same respective PROTACs, suggesting therefore that the subcellular context of the POI can influence the efficacy of PROTAC-mediated POI degradation. , this epimer compound provides a valuable negative control compound for future chemical biology studies. 4b). Mangano et al. The linkage of SLF to the ubiquitin E3 ligase ligand KB02 results in the formation of KB02-SLF. FKBP12 PROTAC dTAG-7 (dTAG-7) also is a selective degrader of BET bromodomain transcriptional co-activator BRD4 by bridging BET bromodomains to an E3 ubiquitin ligase CRBN[1]. FKBP12 PROTAC FM4 is a PROTAC degrader of MTH1, with a DC50 values of 0. May 14, 2024 · The PROTAC induces the proximity of both the target protein and the E3 ligase, resulting in polyubiquitination of the target and its subsequent degradation by the eukaryotic proteasome. FKBP12 PROTAC dTAG-7 (dTAG-7) is a heterobifunctional compound that selectively degrades the BET bromodomain transcriptional co-activator BRD4 by linking BET bromodomains to the E3 ubiquitin ligase CRBN. Genetic perturbations are limited by off-target effects, multi-component complexity, and irreversibility. * Please be kindly noted that our services and products can only be used for research to organizations or companies and not intended for any FKBP12 PROTAC RC32; CAS Number: 2375555-66-9; find AA BLOCKS, INC. continued to develop a series of FKBP12 PROTACs, with thalidomide and a FKBP12 inhibitor, of which PROTAC 29 (Table 17) showed high efficiency for FKBP12 degradation [117]. FKBP12 PROTAC RC32 contains conjugation of Rapamycin (HY-10219) and a ligand for an Cereblon E3 ubiquitin ligase (Pomalidomide; HY-10984)[1]. Crystal structure of a binary FKBP12-PROTAC complex reveals the structural basis for negative cooperativity. Online ahead of print. It acts as a tool to degrade target proteins, allowing scientists to study their functions. 1700. MC-25B degrades FKBP12 with a DC50 of 0. May 7, 2022 · 相比传统的PROTAC技术（通过与E3泛素连接酶和靶蛋白形成三元复合物来发挥降解作用），标签靶向蛋白降解剂（tag-TargetedProteinDegrader，tTPD）有着独特的作用机制，如dTAGs通过识别FKBP12F36V而不是靶蛋白来发挥降解作用，HaloPROTACs通过识 Nov 9, 2023 · Here, we report the discovery of the first FKBP51 Proteolysis targeting chimera (PROTAC) that enables degradation of FKBP51 abolishing FKBP51’s scaffolding function. Jul 9, 2019 · In vitro, dTAG-13 has been shown to lead to rapid and potent degradation of BRD4-FKBP12 F36V, with no effect on endogenous wild type FKBP12, BRD2 or BRD3 levels. Biological Activity for dTAG-13 dTAG-13 is a degrader targeting mutant FKBP12 F36V fusion proteins. Its application in research includes understanding protein interactions and developing new therapeutic strategies. 2022 May 27;7 (1):163. Home Small Molecules & Compound Libraries Signaling Pathways Apoptosis FKBP FKBP12 PROTAC dTAG-13 - 99%, high purity , CAS No. A shortcoming of the PROTAC approach is that it requires a specific degrader ligand for each protein. FKBP12 PROTAC RC32 (RC32) is a potent FKBP12 degrader based on PROTAC technology. Store at Store at -20°C,Desiccated. Proteolysis targeting chimera (PROTAC) technology has become a powerful strategy in drug discovery, especially for undruggable targets/proteins. Purity:>98% Medchemexpress has over 10000 novel life FKBP12 PROTAC dTAG-13 (dTAG-13), a PROTAC-based heterobifunctional degrader, is a selective degrader of FKBP12F36V with expression of FKBP12F36V in-frame with a protein of interest. This product is ready for conjugation to target proteins for PROTAC R&D. We first characterized the efficiency of Haematologica. SLF binds ubiquitin E3 ligase ligand KB02 via a linker to form KB02-SLF. FKBP12 PROTAC dTAG-13 is a bifunctional PROTAC® degrader targeting mutant FKBP12F36V fusion proteins, consisting of a ligand selective for F36V single-point mutated FKBP12 conjugated to a cereblon ligand by a linker. The dTAG technique involves the expression of a protein of interest as a fusion with mutant FKBP12 F36V via transgene expression or CRISPR-mediated locus-specific knock-in. Molecular Weight 1426. FKBP12 PROTAC dTAG-7 targets FKBP12F36V and BET BRD4. 2024. FKBP12 PROTAC RC32 is a PROTAC-like degrader targeting FKBP12. KB02-SLF is a previous reported PROTAC that degrades FKBP12 in an DCAF16-dependent manner 11. Jun 17, 2019 · An electrophilic PROTAC that degrades nuclear FKBP12 We have recently introduced chemical proteomic platforms for globally and site-specifically mapping the reactivity of electrophilic small May 27, 2022 · PROTAC mediated FKBP12 degradation enhances Hepcidin expression via BMP signaling without immunosuppression activitySignal Transduct Target Ther. Native MS combined with collision-induced dissociation (CID) provided a way of measuring not only the formation of these complexes but also their dissociation pathways. It recruits the E3 ligase cereblon to selectively degrade FKBP12-tagged proteins. Jul 4, 2024 · This derivative displayed a similar ability to degrade FKBP12 when incorporated into a PROTAC. Available now at Aladdin Scientific. doi: 10. ,Harvard Nov 25, 2020 · The FK506-binding protein 12 (FKBP12) is a ubiquitous abundant protein that acts as a receptor for the immunosuppressant drug FK506l FK506 binds tightly to intracellular calcium release channels and to the TGF-β type I receptor. Biological Activity for dTAG-7 dTAG-7 is a first generation Degrader for mutant FKBP12 F36V fusion proteins. The attractive prospects of PROTACs have spawned several biopharmaceutical companies. FKBP12 PROTAC dTAG-13 (dTAG-13) is an in vivo-active heterobifunctional adation tag (dTAG) small molecule that engage FKBP12F36V and CRBN. . 10-SLF selectively reduces FKBP12 levels in cells expressing FBXW7-R465C. Application of dTAG-7 induces rapid, reversible and selective degradation of FKBP12 F36V fusion proteins in vitro and in vivo. The cytoplasmic FKBP isoforms FKBP12 and 12. Buy PROTAC inhibitor FKBP12 PROTAC dTAG-7 (dTAG-7) from AbMole BioScience. Differentially localized proteins displayed varying levels of degradation using the same respective PROTACs, suggesting that the subcellular context of the target protein can influence the efficacy of PROTAC-mediated POI degradation. FKBP12 PROTAC dTAG-13 (dTAG-13),CAS:2064175-41-1. By transgene expression or CRISPR-mediated locus-specific knock-in, we exemplify a generalizable strategy to study the immediate consequence of protein loss. We synthesized two heterobifunctional compounds – YT41R (7) and YT47R (9) – that connected MY-1B to the small molecule SLF (Figure 3A), which is a high-affinity ligand for FKBP12 that is frequently used for assessing PROTAC performance 15 – 16, 34 – 37. b Docking mode of RC32 binding to FKBP12 and recruiting CRBN. (Pink: FKBP12 ligand (HY-170988); Blue: E3 ligase ligand HY-170986); Black: linker (HY-128844); FKBP12 ligand+ linker (HY-170987)). Store at Store at -80°C. (B) Structure of WDR5-Luc-FKBP12 and Luc-WDR5-FKBP12 fusion proteins. Aug 30, 2025 · FKBP12 PROTAC RC32(Tsinghua University): a FKBP1A degraders, Proteolysis Drug, Initially developed by Tsinghua University, Now, its global highest R&D status is Pending, Mechanism: FKBP1A degraders(FK506-binding protein 1A degraders),Proteolysis, Therapeutic Areas: Neoplasms. No:I018138) is a small molecule drug conjugate designed to target and degrade proteins of interest using the proteolysis targeting chimera (PROTAC) technology. Description FKBP12 PROTAC FM4 is a PROTAC degrader of MTH1, with a DC50 values of 0. Jun 12, 2023 · Structural analysis of a binary FKBP12:PROTAC complex revealed the molecular basis for negative cooperativity. 287047. It can degrade FKBP12 in organs after intraperitoneal administration. VHL-recruiting dTAG molecules promote ternary complex formation between the FKBP12 F36V -tagged target protein and E3 FKBP12 PROTAC RC32, also known as RC32, is a powerful FKBP12 degrader developed using PROTAC (Proteolysis Targeting Chimera) technology. Building blocks of PROTAC molecules include PROTAC Linker, Ligand for Target Protein for PROTAC, Ligand for E3 Ligase, E3 Ligase Ligand-Linker Conjugate, Target Protein Ligand-Linker Conjugate, etc. It also functions as a degrader of FKBP12F36V when FKBP12F36V is expressed in-frame with a targeted protein. Dec 4, 2023 · Briefly, FKBP12 F36V binding molecules compete with an FKBP12 F36V targeting PROTAC (dTAG-13), for NLuc-FKBP12 F36V occupancy, rescuing degradation and resulting in an increase in NLuc/FLuc Apr 24, 2024 · 150 While these results suggest that the respective E3 ligase ubiquitylates the target protein 151 (WDR5 or Aurora A), it cannot be excluded that luciferase or FKBP12 could also serve as a 152 substrate for ubiquitylation. FKBP12 PROTAC RC32 (RC32) is a potent FKBP12 degrader based on PROTAC technology. Moiety in red, linker; moiety in blue, rapamycin 其中小鼠及大鼠体内FKBP12蛋白仅用一天，香猪体内FKBP12仅用两天，恒河猴体内FKBP12仅用三天即可全身高效率全身敲低。 此外，本文中首次验证PROTACs可在口服给药途径中保持高效蛋白降解功能。 脑室给予PROTACs时可实现脑内FKBP12的条件性敲除。 Mar 1, 2025 · Therefore, in this study, we asked if degrading mutant IDH1 by employing a PROTAC-based approach leads to STAT3 activation. 22 nM. Dec 6, 2024 · A rapamycin-induced proximity assay enables rapid identification of optimal E3 ligases for target protein degradation in living cells, streamlining early-stage proteolysis targeting chimera development. FKBP12 PROTAC FM4 is composed of PROTAC target protein ligand AP1867-3-(aminoethoxy) (HY-129363) (red part), E3 ligase ligand MTH1 ligand 1 (HY-134724) (blue part) and PROTAC Linker t-Boc-N-amido-PEG5-acetic acid (HY-W190962) (black part), among which the conjugate of PROTAC target protein ligand Biological Activity FKBP12 PROTAC dTAG-13 (dTAG-13), a PROTAC-based heterobifunctional degrader, is a selective degrader of FKBP12F36V with expression of FKBP12F36V in-frame with a protein of interest. It uses a dTAG-13 group to engage FKBP12F36V and CRBN, triggering fast degradation via the proteasome, ideal for protein research and drug development. Mar 25, 2025 · Description: FKBP12 PROTAC dTAG-13 (dTAG-13) is a PROTAC-based heterobifunctional degrader. 2064175-41-1 KB02-SLF is a PROTAC-based nuclear FKBP12 degrader (molecular glue). Our study, therefore, suggested that PROTAC-mediated FKBP12 degradation could be a novel and safe approach to treat iron overload diseases resulting from low hepcidin. Dissecting complex biological systems requires target-specific control of protein function or abundance. KB02-SLF promotes nuclear FKBP12 degradation by covalently modifying DCAF16 (E3 ligase). FKBP12 inhibits the basal signaling of these three receptors and also regulates the P-glycoprotein multidrug Jan 15, 2025 · Here, we studied two MG-induced complexes between mTOR FRB and FKBP12 as well as a PROTAC-induced complex between FKBP51 FK1 and the von Hippel-Lindau E3 ligase (VHL). 1 Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology - NTNU, Trondheim. Nov 4, 2020 · KB02-SLF is a PROTAC-based nuclear FKBP12 degrader (molecular glue). Comprises a ligand selective for F36V single-point mutated FKBP12, a linker and a cereblon-binding ligand. Aug 30, 2025 · FKBP12 PROTAC dTAG-7 (Dana-Farber Cancer Institute): a FKBP1A degraders, Proteolysis Drug, Initially developed by Dana-Farber Cancer Institute, Inc. * Please be kindly noted that our services and products can only be used for research to organizations or companies and not intended for any clinical or individuals. Buy FKBP12 PROTAC dTAG-13 with 10mM in DMSO. Purchase FKBP12 PROTAC RC32 with . 1-1000 nM; for 12 hours) results in 50% protein degradation (DC50) of ~0. We therefore see an urgent need for genetic assays that allow us to identify suitable target/E3 ligase pairs. FKBP12 PROTAC RC32 is an effective degrader utilizing PROTAC technology. Oct 9, 2024 · To determine the chemical requirements for PXR activation by dTAG-13, we next tested five dTAG-13-related compounds (three PROTAC analogs and two FKBP12 F36V ligands) for PXR modulation (Figure 3 A). Mar 5, 2023 · Arvinas’ AR PROTAC ARV-110 and ER PROTAC ARV-471 have recently demonstrated satisfactory safety and tolerability in patients in Phase I and II clinical trials, respectively. Jul 14, 2020 · Work published while this study was under review utilizing a KRAS G12C -specific PROTAC harboring a CRBN recruiting warhead was able to demonstrate the degradation of GFP-K-RAS, but the PROTAC was unable to degrade endogenous or untagged K-RAS (Zeng et al. FKBP12 PROTAC dTAG-13 (dTAG-13) also is a selective degrader of BET bromodomain transcriptional co-activator BRD4 by bridging BET bromodomains to an E3 ubiquitin ligase CRBN. In this context, the dTAG-13 proteolysis targeting chimera (PROTAC) was used to degrade FKBP12 F36V -tagged K-RAS (Nabet et al. FKBP12 PROTAC dTAG-7 (dTAG-7) also is a selective degrader of BET bromodomain transcriptional co-activator BRD4 by bridging BET bromodomains to an E3 ubiquitin ligase CRBN. , 2018) through the UPS, albeit when overexpressed in cells. dFKBP-1 is a potent and PROTAC-based FKBP12 degrader. 6 für FKBP51). 6 and the nuclear FKBP25 and 133 contain a single PPIase domain. Application of dTAG-13 induces rapid, reversible and selective degradation of FKBP12 F36V fusion proteins in vitro and in vivo. Apr 19, 2022 · FKBP12 F36V, NanoLuc or Halo epitope tags are fused to proteins of interest (POI) and tag-targeting heterobifunctional degrader compounds are employed to hijack cullin-RING ligase (CRL) complexes FKBP12 PROTAC dTAG-13 | C57H68N4O15 | CID 124187630 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more. B. FKBP12 PROTAC FM4 is composed of PROTAC target protein ligand AP1867-3-(aminoethoxy) (HY-129363) (red part), E3 ligase ligand MTH1 ligand 1 (HY-134724) (blue part) and PROTAC Linker t-Boc-N-amido-PEG5-acetic acid (HY-W190962) (black part), among which the conjugate of PROTAC target protein ligand + Linker is FKBP12 Ligand FKBP12 PROTAC dTAG-7 (dTAG-7) is a heterobifunctional PROTAC degrader. A) FKBP12_eGFP reporter degradation after 48 h treatment at 1 μM PROTAC. Buy FKBP12 PROTAC dTAG-7 with 99%. Halo protein localized to the cytoplasmic surface of Golgi was amenable for degradation, whereas VHL and CRBN-based PROTACs failed to degrade Golgi lumen localized Halo or FKBP12 F36V proteins. FKBP12 PROTAC RC32 (RC32; 0. 71. Download scientific diagram | Evaluation of additional factors that might influence PROTAC-mediated target protein degradation (A and B) U2OS cells expressing either FLAG-NLS-FKBP12 F36V -HiBiT or Sep 1, 2021 · Subsequently, Nabet et al. FKBP12 PROTAC dTAG-13 (dTAG-13), a PROTAC-based heterobifunctional degrader, is a selective degrader of FKBP12F36V with expression of FKBP12F36V in-frame with a protein of interest. Browse FKBP12 PROTAC RC32 and related products at MilliporeSigma. Oct 20, 2022 · Because we describe the synthesis of a dTAG-VHL PROTAC and demonstrate degradation of FLAG-FKBP12 F36V -HiBiT and FLAG-NLS-FKBP12 F36V-HiBiT proteins in cells, we sought to validate its mode of action and tolerability in cells. 09–0. Ideal for , this reagent supports . May 17, 2025 · Lines indicate dose-dependent reduction of MYC expression. Most limiting is the requisite delay FKBP12 PROTAC dTAG-13 is a PROTAC and selective degrader for target validation by splicing FKBP12 F36V with CRBN and thereby degrading FKBP12 F36V. HY-114421 5mg FKBP12 PROTAC dTAG-13 CAS: 2064175-41-1 FKBP12 PROTAC dTAG-13 (dTAG-13), a PROTAC-based heterobifunctional degrader, is a selective degrader of FKBP12F36V with expression of FKBP12F36V in-frame with a protein of interest. This design allows RC32 to recruit the E3 ubiquitin ligase to FKBP12, leading to Mar 5, 2025 · The therapeutic application of targeted protein degradation (TPD) is limited by target degradation in healthy cells. interrogate how the subcellular context of a target protein influences its amenability to PROTAC-mediated degradation. - >99% HPLC purity, ideal for cancer research and epigenetic studies. ChemScene Provide CAS 2064175-41-1, FKBP12 PROTAC dTAG-13, dTAG-13, Formula:C57H68N4O15, MW:1049. IC50 values in the presence or absence of FKBP12 PROTAC are indicated above each panel. May 1, 2022 · PDF | On May 1, 2022, Tianbai Zhong and others published PROTAC mediated FKBP12 degradation enhances Hepcidin expression via BMP signaling without immunosuppression activity | Find, read and cite SLF-amido-C2-COOH (PROTAC FKBP12-binding moiety 1) is a synthetic ligand for FKBP (SLF). FKBP12 PROTAC RC32 contains conjugation of Rapamycin (HY-10219) and a ligand for an Cereblon E3 ubiquitin ligase (Pomalidomide; HY-10984). -TA9H9A9A43F4 MSDS, related peer-reviewed papers, technical documents, similar products & more at Sigma-Aldrich FKBP12 PROTAC dTAG-13 (CAT: I017647) is a small-molecule heterobifunctional degrader designed to target FKBP12 for proteasomal degradation. In fact, luciferase and FKBP12 proteins contain 7 and 8 lysine 153 residues respectively. 5 µM in a FBXO22 dependent manner. Mar 26, 2018 · FKBP12 is artificially recruited to CRL4-CRBN by dFKBP-1, leading to degradation of FKBP12. Quality confirmed by NMR,HPLC & MS. 2c, d). Aug 1, 2025 · ChemicalBook 致力于为化学行业用户提供FKBP12 PROTAC DTAG-13的性质、化学式、分子式、比重、密度,同时也包括FKBP12 PROTAC DTAG-13的沸点、熔点、MSDS、用途、作用、毒性、价格、生产厂家、用途、上游原料、下游产品等信息。 The FK506-binding protein 12 (FKBP12) is a ubiquitous abundant protein that acts as a receptor for the immunosuppressant drug FK506l FK506 binds tightly to intracellular calcium release channels and to the TGF-β type I receptor. 10-SLF is a PROTAC FKBP12 degrader. FKBP12 PROTAC dTAG-7 enables rapid and selective degradation of target proteins, and is suitable for cellular and in vivo studies to analyze protein functions and validate targets [1]. [5] It is also commonly referred to as FKBP-12 or FKBP12 and is a member of a family of FK506 -binding proteins (FKBPs). In brief Simpson et al. 3 nM after only 12 hours of treatment [1]. FKBP12 PROTAC dTAG-13 effectively engages FKBP12F36V and CRBN, thereby selectively degrading FKBP12F36V. dFKBP-1 incorporates the ligand SLF (HY-114872) of FKBP12, the Thalidomide based Cereblon ligand and a linker. Apr 17, 2025 · Novel PROTAC to target FKBP12: the potential to enhance bone morphogenetic protein activity and apoptosis in multiple myeloma RC32-induced degradation of FKBP12 in cell cultures. -AABH9A95AF4C MSDS, related peer-reviewed papers, technical documents, similar products & more at Sigma-Aldrich FKBP12PROTACFM4 is a PROTAC degrader targeting MTH1, with a degradation efficiency (Dmax) greater than 90%. . FKBP12 PROTAC RC32; CAS Number: 2375555-66-9; find Targetmol Chemicals Inc. It can useful for target validation in the context of drug discovery. Having identified DCAF11 as an E3 ligase responsible for mediating the degradation of FKBP12 by 21-SLF, we wondered whether other screening hits from the electrophilic PROTAC library might also act through DCAF11. For use within . : Dana-Farber Cancer Institute, Inc. 3324/haematol. FKBP12 PROTAC dTAG-13 (dTAG-13) is a novel and potent PROTAC degrader for degradation of FKBP12F36V fusion chimeras. May 27, 2022 · Our results revealed that PROTAC-mediated FKBP12 degradation is an ideal strategy to upregulate hepcidin expression without immunosuppression activity. KB02-SLF represents a molecular glue-derived nuclear FKBP12 degrader built on the PROTAC framework. The Crews group, which first reported the application of PROTACs, recently constructed FKBP12 F36V binding PROTACs to find new E3 ubiquitin ligases as PROTAC targets. - Mechanism of Action & Protocol. KB02-SLF promotes nuclear FKBP12 degradation by covalently modifying DCAF16 (E3 ligase) and can improve the durability of protein degradation in biological systems. FKBP12 PROTAC dTAG-13 (CAS: 2064175-41-1) is a selective PROTAC designed to degrade FKBP12F36V fusion proteins and mutant FKBP12. FKBP12 PROTAC dTAG-7 (dTAG-7) is a cell-permeable heterobifunctional adation tag (dTAG) small molecule that engage FKBP12F36V and CRBN, selectively degrade FKBP12F36V in a CRBN-dependent manner in cells. To answer the question, we adopted the dTAG system, where we fused FKBP12 F36V to mutant IDH1 proteins and used the FKBP12 F36V -specific PROTAC, dTAG-13, to degrade mutant IDH1-FKBP12 F36V. MC-25B is a specific FKBP12 PROTAC degrader. CAS 2375555-66-9. Nov 20, 2024 · (A) Schematic illustration of rapamycin-induced dimerization of FRB and FKBP12 and structure of rapamycin. c Chemical structure FKBP12 PROTAC RC32 (RC32) is a potent FKBP12 degrader based on PROTAC technology. PROTAC技术可以使用双靶点构建，双靶点设计PROTAC的概念即通过选择特定的E3,使PROTAC在降解靶蛋白一的同时,因PROTAC对E3的竞争导致该E3天然底物蛋白的降解受阻,即靶蛋白二的升高。采用该方法,构建了不仅能够靶向泛… Jan 1, 2022 · Targeted protein degradation (TPD) is a rapidly developing field in chemical biology and drug discovery. FKBP12 PROTAC dTAG-7 shows potential for targeted protein degradation in research and therapeutic applications. FKBP12 PROTAC dTAG-7 (dTAG-7),CAS:2064175-32-0. We tested 2G07-SLF in HEK293T cells overexpressing HA-DCAF16 and nucleus-localized FKBP12 (FKBP12_NLS) and observed a dose-dependent reduction in FKBP12_NLS (Fig. FKBP12 PROTAC RC32 contains conjugation of Rapamycin and a ligand for an E3 ubiquitin ligase (Pomalidomide;) [1]. Fkbp12 protac RC32 | C75H107N7O20 | CID 146026069 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more. SLF-amido-C2-COOH (PROTAC FKBP12-binding moiety 1) can be used in the synthesis of PROTACs. FKBP12 PROTAC dTAG-7 (dTAG-7) is a degrader of FKBP12F36V with expression of FKBP12F36V in-frame with a protein of interest. Various TPD modalities have emerged, with proteolysis-targeting chimeras (PROTACs) being the most well-developed at present. dTAG-7 differs from dTAG-13 only in the linker composition, dTAG V -1 differs only in the E3 ligand, and PROTAC FKBP degrader-3 (FKBP Deg 3 Nov 9, 2023 · Structural analysis of a binary FKBP12:PROTAC complex revealed the molecular basis for negative cooperativity. MC-25B facilitates the degradation of nuclear-localized FKBP12 through a DCAF16-dependent mechanism. FKBP12 PROTAC dTAG-51(Dana-Farber Cancer Institute): a FKBP1A degraders Drug, Initially developed by Dana-Farber Cancer Institute, Inc. Initial synthesis of 220 FKBP-focused PROTACs yielded a plethora of active PROTACs for FKBP12, six for FKBP51, and none for FKBP52. 10-SLF induces a ternary complex between FKBP12 and FBXW7-R465C, and promotes FBXW7-R465C-dependent proteasomal degradation of FKBP12. Download scientific diagram | Discovery of an electrophilic PROTAC that promotes the loss of nuclear FKBP12 a, Structures of electrophilic bifunctional compounds, or PROTACs, containing scout FKBP12 PROTAC RC32 contains conjugation of Rapamycin and a ligand for an E3 ubiquitin ligase. a Mechanism of action of PROTAC. This compound enhances the degradation of nuclear FKBP12 by covalently altering DCAF16 (the E3 ligase), thereby bolstering the resilience of protein degradation within biological systems. Order now for fast global shipping and technical support. FKBP12, the 12-kDa FK506-binding protein, is a ubiquitous abundant protein that acts as a receptor for the immunosuppressant drug FK506, binds tightly to intracellular calcium release channels and to the transforming growth factor β (TGF-β) type I FKBP12 PROTAC RC32 (RC32) is a potent FKBP12 degrader based on PROTAC technology. dTAG is generalizable to a range of fusion proteins; useful FKBP12 PROTAC dTAG-13 contains a dTAG-13 group used for targeting and degrading the mutant FKBP12F36v fusion proteins and a single-point mutated FKBP12. It combines Rapamycin with a Cereblon E3 ubiquitin ligase ligand to facilitate targeted degradation of FKBP12, enhancing the specificity and efficacy of the degradation process. dTAG is generalizable to a range of fusion proteins Dec 18, 2023 · Current proteolysis-targeting chimeras can promote the ubiquitination and subsequent degradation of both target and off-target proteins by inducing their respective proximity with the cereblon FKBP12 PROTAC dTAG-7 is a chemical compound used in scientific research. , 2020 ). Oct 20, 2022 · Moreover, PROTAC accessibility to target proteins is also critical for PROTAC-mediated degradation. 125 aktive PROTAC-Treffer für FKBP12 vs. Sep 18, 2020 · a Schematic depiction of the dTAG system using VHL-recruiting dTAG molecules. , Now, its global highest R&D status is Pending, Mechanism: FKBP1A degraders (FK506-binding protein 1A degraders), Therapeutic Areas: Neoplasms,Hemic and Lymphatic Diseases. dTAG-13 (FKBP12 PROTAC dTAG-13) is an ortho-substituted, heterobifunctional selective degrader of FKBP12F36V that effectively engage FKBP12F36V and CRBN leading to rapid and selective CRBN-mediated degradation of FKBP12F36V. Taken together, these results indicate that knockdown of FKBP12 in mice via the designed PROTAC is a valuable model for studying FKBP12 function, especially in the heart. FKBP12 PROTAC RC32. , Now, its global highest R&D status is Pending, Mechanism: FKBP1A degraders (FK506-binding protein 1A degraders),Proteolysis, Therapeutic Areas: Neoplasms,Hemic and Lymphatic Diseases. Jul 4, 2024 · We confirmed the degradation of FKBP12-EGFP using lenalidomide–SLF (Len–SLF; synthetic ligand of FKBP) (Extended Data Fig. In PROTACs, a heterobifunctional molecule is used to recruit an E3 ligase to degrade a protein of therapeutic interest. Sep 7, 2022 · Simpson et al. 4a). 1b,c), an established PROTAC targeting FKBP12 through recruiting CRBN 12. Linker-based optimization of first generation FKBP51 PROTACs led to the PROTAC SelDeg51 with improved cellular activity, selectivity, and high cooperativity. We first characterized the efficiency of RC32-induced FKBP12 degradation in hepatocellular carcinoma (HCC) cell lines. fqboi parr knc ykhr lwjp kjg jrl nrg qoohoq bxc