Ask about this productRelated genes to: BRDT antibody
- Gene:
- BRDT NIH gene
- Name:
- bromodomain testis associated
- Previous symbol:
- -
- Synonyms:
- BRD6, CT9
- Chromosome:
- 1p22.1
- Locus Type:
- gene with protein product
- Date approved:
- 1997-08-15
- Date modifiied:
- 2016-03-03
Related products to: BRDT antibody
Related articles to: BRDT antibody
- The engineered formation of ternary complexes, in which two proteins are bridged by small molecules such as PROTACs or molecular glues, is a prerequisite for the targeted enzymatic degradation of pathogenic proteins; however, the combined analysis of these ternary interactions during the drug discovery process remains challenging. Here, we introduce a proximity binding assay for the simultaneous measurement of binary and ternary interaction kinetics on a biosensor surface. Target proteins and the substrate binding subunit of ubiquitin E3 ligase are tethered to mobile swivel arms of a Y-shaped DNA scaffold. The Y-structure induces spatial proximity between the proteins and presents them to PROTAC analytes flown across the sensor. PROTAC-induced ternary complex formation is measured by fluorescence energy transfer (FRET), while binary interactions are detected by fluorescence quenching. The assay is applied to cereblon (CRBN) and von Hippel-Lindau (VHL) as E3 ligase substrate receptors, a range of compounds including AT1, MZ1, dBETs, and ARV-825 as PROTACs, and the two bromodomains of BRD2, BRD3, BRD4, and BRDT proteins as targets. Automated workflows enable the measurement of 384 real-time sensorgrams in a single run using picomole sample quantities. The insights into proximity-mediated binding kinetics can enable the development of PROTACs and molecular glues with improved properties for targeted protein degradation. - Source: PubMed
Publication date: 2026/04/21
Ponzo IreneSoldà AliceCrowe CharlotteDahl GöranJahodová TerezaHeerwig AndreasGeschwindner StefanCiulli AlessioRant Ulrich - The first bromodomain of the BET protein BRDT (BRDT-BD1) possesses a unique Arg54 residue at the terminus of the ZA channel, absent in other BET family members. We explored this structural uniqueness with 23 analogs of the BET/kinase inhibitor , each bearing an amino acid side chain to enable potential interactions between the positively charged arginine group and the negatively charged carboxylate groups. In an AlphaScreen assay, serine analog showed 35-fold selectivity for BRDT-T over BRD4-T. The BRDT-BD1 cocrystal structure with glutamic acid analog showed no interaction with Arg54, suggesting that the observed preference may be related to differences in the structured water molecules. Compound displayed exceptional in vitro metabolic stability but had limited cellular permeability in MDCK-MDR1 cells. Compounds and are among the best BRDT-BD1-preferring inhibitors reported to date and demonstrate a significant step toward identifying highly selective BRDT inhibitors for male contraception. - Source: PubMed
Publication date: 2026/04/15
Liang TaimengGuan XianghongChan AliceKalra PrakritiShi RuiSolberg JonathanSigua Logan HQi JunPomerantz William C KSchönbrunn ErnstHawkinson Jon EGeorg Gunda I - Developing safe, reversible, and nonhormonal male contraceptives has been hindered by the lack of defined biological windows that can be transiently interrupted without compromising long-term fertility. Here, we tested whether meiotic prophase I can serve as such a window by pharmacologically inhibiting the testis-specific chromatin reader BRDT using the small-molecule bromodomain inhibitor (+)-JQ1 as proof-of-principle. Short-term JQ1 administration (3 wk) selectively disrupted the pachytene transcriptional program, depleted postmeiotic germ cells, and induced a reversible arrest in spermatogenesis. Upon drug withdrawal, prophase I cytological markers normalized within 6 wk, accompanied by restoration of testis architecture and germ-cell composition. Crossover metrics and transcriptional programs recovered more gradually, reaching full normalization by 30 wk alongside complete restoration of fertility and fecundity. These results demonstrate that meiotic prophase I can be transiently inhibited to suppress spermatogenesis reversibly without inducing lasting genomic or reproductive defects, defining a stage-specific framework for the rational design of nonhormonal male contraceptives. - Source: PubMed
Publication date: 2026/04/07
Tanis StephanieSimon Leah EAlexander Adriana KHoran Tegan SCarro Maria de Las MercedesBonnett Samantha JaneXie AudreyBen-Shlomo RoniOwens Connor EDanko Charles GLujic JelenaCohen Paula E - Arthritis is an inflammatory condition that affects the joints and surrounding tissues, triggered by factors such as inflammation, infection, degeneration, and trauma. The major forms of arthritis include osteoarthritis (OA), rheumatoid arthritis (RA), and gouty arthritis (GA). Its pathogenesis primarily involves synovial inflammation, cartilage degradation, and subchondral bone remodeling, with pro-inflammatory cytokines, collagenases, and other mediators playing central roles in disease onset and progression. The bromodomain and extraterminal (BET) protein family-a subclass of the larger bromodomain protein superfamily-comprises BRD2, BRD3, BRD4, and BRDT. The regulatory functions of BET proteins in inflammation highlight their considerable potential for mitigating arthritis-related pathology. This review provides a comprehensive overview of recent research on the role of BET proteins in OA, RA, and GA, aiming to deepen our understanding of the protective mechanisms of BET inhibitors, underscore their potential as therapeutic targets, and emphasize their relevance in the development of novel treatment strategies. - Source: PubMed
Publication date: 2025/09/30
Sheng WeibeiZhao JinYu FeiWang DeliZeng HuiLiu Peng - Chemical Inducers of Proximity DNA-Encoded Library (CIP-DEL) screening enables high-throughput discovery of compounds that induce protein-protein interactions, including Proteolysis-Targeting Chimeras (PROTACs). Simultaneous screening of protein paralogs with CIP-DEL allows profiling of compound selectivity and efficient identification of paralog-selective degraders, but such an application has not been reported. Here, we optimized CIP-DEL screening conditions and conducted a von Hippel-Lindau (VHL)-biased CIP-DEL screen with two million DNA-barcoded PROTAC compounds on eight closely related Bromodomain and Extra Terminal domain (BET) bromodomains: BRD2 BD1, BRD2 BD2, BRD3 BD1, BRD3 BD2, BRD4 BD1, BRD4 BD2, BRDT BD1, and BRDT BD2. We observed a marked tendency of compounds to bind the first bromodomain (BD1) preferentially over the second bromodomain (BD2), which contrasts with the predominantly BD2-selective inhibitors reported in the literature. Specifically, our screening approach yielded compound , which demonstrated promising BRD2 BD1 selectivity in both sequencing data of DEL screening output and in vitro assays. Additionally, normalized relative enrichment selectivity from sequencing data rather than unnormalized absolute enrichment selectivity correlated more closely with experimentally validated selectivity. Overall, we highlight the value of CIP-DEL in profiling PROTAC selectivity, which should be applicable to other protein families with high sequence homologies, where selective degrader discovery remains challenging. - Source: PubMed
Publication date: 2025/08/12
Chow Yuen TingTong BingqiTan Zher YinTutter AntoninNan ZhihanHorton Patricia ARomanowski Michael JZécri Frédéric JSchreiber Stuart LLiu Shuang