dTRIM24
目录号 : GC35904dTRIM24 是一种选择性的双功能基于 PROTAC 技术的 TRIM24 降解剂。
Cas No.:2170695-14-2
Sample solution is provided at 25 µL, 10mM.
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- Purity: >99.50%
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Cell experiment: | MOLM-13 cells are seeded at 30,000 cells/well. Growth over time of MOLM-13 cells treated with 5?μM of indicated compounds (e.g., dTRIM24) over 7 d. At endpoints, cells are suspended and mixed with Viacount reagent at 1:3. The mixture is incubated for 5?min, and viable cells are counted on the Guava easycyte flow cytometer. Means from three technical replicates of cell counts are calculated[2]. |
References: [1]. Gechijian LN, et al. Functional TRIM24 degrader via conjugation of ineffectual bromodomain and VHL ligands. Nat Chem Biol. 2018 Apr;14(4):405-412. |
dTRIM24 is a selective bifunctional degrader of TRIM24 based on PROTAC. TRIM24[2].
dTRIM24 is a degrader of TRIM24 bromodomain. Recruitment of the VHL E3 ubiquitin ligase by dTRIM24 elicits potent and selective degradation of TRIM24. The anti-proliferative consequences of chemical degradation versus inhibition of TRIM24 are assessed. Growth over time is determined for MOLM-13 cells treated with dTRIM24, IACS-9571, VL-269, and eTRIM24. dTRIM24 suppresses growth to a greater extent than does IACS-9571, accompanied by apoptosis measured as enhanced PARP cleavage. In agreement with a sustained proliferative defect observed following dTRIM24 treatment, near-complete degradation of TRIM24 is observed in dTRIM24-treated cells throughout the duration of the experiment[2].
[1]. Gechijian LN, et al. Functional TRIM24 degrader via conjugation of ineffectual bromodomain and VHL ligands. Nat Chem Biol. 2018 Apr;14(4):405-412.
Cas No. | 2170695-14-2 | SDF | |
Canonical SMILES | CN(C(N1C)=O)C2=C1C=C(OC3=CC=CC(OCCC)=C3)C(NS(C4=CC(C(NCCOCCOCCOCC(N[C@H](C(N5[C@H](C(NCC6=CC=C(C7=C(C)N=CS7)C=C6)=O)C[C@@H](O)C5)=O)C(C)(C)C)=O)=O)=CC=C4)(=O)=O)=C2 | ||
分子式 | C55H68N8O13S2 | 分子量 | 1113.3 |
溶解度 | Ethanol: < 1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
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10 mM | 0.0898 mL | 0.4491 mL | 0.8982 mL |
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Functional TRIM24 degrader via conjugation of ineffectual bromodomain and VHL ligands
Nat Chem Biol 2018 Apr;14(4):405-412.PMID:29507391DOI:10.1038/s41589-018-0010-y.
The addressable pocket of a protein is often not functionally relevant in disease. This is true for the multidomain, bromodomain-containing transcriptional regulator TRIM24. TRIM24 has been posited as a dependency in numerous cancers, yet potent and selective ligands for the TRIM24 bromodomain do not exert effective anti-proliferative responses. We therefore repositioned these probes as targeting features for heterobifunctional protein degraders. Recruitment of the VHL E3 ubiquitin ligase by dTRIM24 elicits potent and selective degradation of TRIM24. Using dTRIM24 to probe TRIM24 function, we characterize the dynamic genome-wide consequences of TRIM24 loss on chromatin localization and gene control. Further, we identify TRIM24 as a novel dependency in acute leukemia. Pairwise study of TRIM24 degradation versus bromodomain inhibition reveals enhanced anti-proliferative response from degradation. We offer dTRIM24 as a chemical probe of an emerging cancer dependency, and establish a path forward for numerous selective yet ineffectual ligands for proteins of therapeutic interest.
Pharmacological targeting of Tripartite Motif Containing 24 for the treatment of glioblastoma
J Transl Med 2021 Dec 9;19(1):505.PMID:34886858DOI:10.1186/s12967-021-03158-w.
Glioblastoma (GBM) is the most aggressive brain tumor of the central nervous system. Recent studies have reported the crucial functions of Tripartite Motif Containing 24 (TRIM24) in promoting cancer progression of GBM. However, it remains unclear if TRIM24 is an attractive druggable target for therapeutic intervention in GBM. We therefore performed a series of experiments, aiming to verify whether specific TRIM24 inhibition suppresses GBM malignant functions using dTRIM24 and IACS-9571, two novel selective TRIM24 antagonists. Our data showed that TRIM24 inhibitors serve as effective agents for inhibiting cell propagation and invasion of several patient-derived GBM stem cells (GSCs), and these effects are mediated partially through suppression of the TRIM24-SOX2 axis. This study provides novel insight into the TRIM24-based druggable dependencies, important for developing effective therapeutic strategies for brain tumors.