Name: PROTAC BET Degrader-1
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

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Stock

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$--

In stock

Solubility

DMSO : ≥ 50 mg/mL (57.35 mM)

Storage

Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month

Shipping

Room temperature in continental US; may vary elsewhere

Synonyms

4-[(5-cyclopropyl-2-ethylpyrazol-3-yl)amino]-7-(3,5-dimethyl-1,2-oxazol-4-yl)-N-[4-[[2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyacetyl]amino]butyl]-6-methoxy-9H-pyrimido[4,5-b]indole-2-carboxamide

InChI Key

TXLUZGFDBDQACL-UHFFFAOYSA-N

InChI

InChI=1S/C44H45N11O9/c1-5-54-32(19-27(52-54)23-11-12-23)48-39-37-25-18-31(62-4)26(35-21(2)53-64-22(35)3)17-28(25)47-38(37)50-40(51-39)42(59)46-16-7-6-15-45-34(57)20-63-30-10-8-9-24-36(30)44(61)55(43(24)60)29-13-14-33(56)49-41(29)58/h8-10,17-19,23,29H,5-7,11-16,20H2,1-4H3,(H,45,57)(H,46,59)(H,49,56,58)(H2,47,48,50,51)

SMILES

CCN1C(=CC(=N1)C2CC2)NC3=NC(=NC4=C3C5=CC(=C(C=C5N4)C6=C(ON=C6C)C)OC)C(=O)NCCCCNC(=O)COC7=CC=CC8=C7C(=O)N(C8=O)C9CCC(=O)NC9=O

Mechanism

Target: Targets BET bromodomain proteins, especially BRD4, BRD3, and BRD2 for experimental targeted protein degradation studies.

Binding Site: Binds the BET bromodomain acetyl-lysine pocket and recruited E3 ligase ligand site to support productive ternary complex formation.

Mechanism of Action: PROTAC BET Degrader-1 is designed for use in PROTAC or targeted protein degradation experiments directed toward BET bromodomain proteins, especially BRD4, BRD3, and BRD2. The bifunctional molecule links a target-recognition element to cereblon, promoting proximity between the protein of interest and ubiquitination machinery. Productive ternary-complex formation can drive polyubiquitination and proteasome-dependent target depletion, allowing researchers to compare pharmacological inhibition with protein removal. It is suitable for evaluating degradation potency, kinetics, pathway selectivity, and downstream signaling consequences in engineered or disease-relevant cellular models.

Applications

• Bet Protein Degradation: PROTAC BET Degrader-1 is designed to selectively target and degrade BET family proteins, including BRD2, BRD3, and BRD4. This application is crucial for studying the role of BET proteins in transcriptional regulation and exploring therapeutic strategies for diseases driven by aberrant BET activity.

• Epigenetic Modulation: By facilitating the targeted degradation of BET proteins, PROTAC BET Degrader-1 provides a powerful tool for investigating epigenetic mechanisms. Researchers can utilize this compound to dissect the influence of BET proteins on chromatin remodeling and gene expression.

• Cancer Biology Research: PROTAC BET Degrader-1 serves as an invaluable resource in cancer biology to elucidate the contribution of BET proteins in oncogenic processes. This application assists in identifying potential vulnerabilities in cancer cells that rely on BET protein functions for survival and proliferation.

• Drug Discovery and Development: Utilizing PROTAC BET Degrader-1 in drug discovery allows researchers to evaluate the therapeutic potential of BET protein degradation. The compound aids in the identification of novel degradation pathways, providing insights that can be leveraged to develop innovative therapeutic agents.

1. General Stepwise Approach to Optimize a TR-FRET Assay for Characterizing the BRD/PROTAC/CRBN Ternary Complex

Wenwei Lin, Taosheng Chen ACS Pharmacol Transl Sci. 2021 Feb 26;4(2):941-952. doi: 10.1021/acsptsci.1c00032.eCollection 2021 Apr 9.

Proteolysis-targeting chimeras (PROTACs) degrade target proteins by engaging the ubiquitin-proteasome system. Assays detecting target-PROTAC-E3 ligase ternary complexes are critical for PROTAC development. Both time-resolved fluorescence energy transfer (TR-FRET) assays and amplified luminescent proximity homogeneous assays can characterize ternary complexes and assess PROTAC efficacy; stepwise optimization protocols for these assays are lacking. To identify assay conditions that can be applied to various targets and PROTACs, we used a stepwise approach to optimize a TR-FRET assay of BRD2(BD1)/PROTACs/CRBN ternary complexes. This assay is sensitive and specific and responds to the bivalent PROTACs dBET1, PROTAC BET Degrader-1, and PROTAC BET Degrader-2 but not to non-PROTAC ligands of BRD2(BD1) or CRBN. The activity rank order of dBET1, PROTAC BET Degrader-1, and PROTAC BET Degrader-2 in the TR-FRET assay corresponded with previously reported cell growth inhibition assays, indicating the effectiveness of our assay for predicting PROTAC cellular activity. The TR-FRET ternary complex formation assay for BRD2(BD1)/PROTAC/CRBN can be configured to characterize the binding activities of BRD2(BD1) and CRBN ligands with the same compound activity rank order as that of previously reported binary binding assays for individual targets but with the advantage of simultaneously assessing the ligand activities for both targets. Our assay is modular in nature, as BRD2(BD1) can be replaced with other BRDs and successfully detect ternary complexes without modifying other assay conditions. Therefore, the TR-FRET ternary complex assay for BRDs provides a general assay protocol for establishing assays for other targets and bivalent molecules.

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Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂