2024年10月1日 · In this review, we have covered the discovery and synthesis of the JQ1 molecule. The SAR of the JQ1 analogs will help researchers develop potent JQ1 compounds with improved inhibitory properties against malignant cells. Furthermore, we explored the potential application of JQ1 analogs in PROTAC technology.

2024年8月16日 · JQ1 类似物的 SAR 将帮助研究人员开发有效的 JQ1 化合物，并改善对恶性细胞的抑制特性。 此外，我们还探讨了 JQ1 类似物在 PROTAC 技术中的潜在应用。 溴结构域蛋白家族的简史以及与 PROTAC 技术相关的障碍可以帮助理解当前研究的背景，这有可能改善药物开发过程。 总的来说，这篇综述全面评价了 JQ1 分子及其在 PROTAC 技术和癌症治疗中的先前实施。 JQ1 is a wonder therapeutic molecule that selectively inhibits the BRD4 signaling pathway and …

The D2B synthesis library was designed using dBET1 (1, Scheme 1) as a model system to investigate linker SAR for degraders. Using JQ1 (2) as the POI ligand linked to CRBN E3 ligase ligands, such as O-linked pomalidomide (O-Pom) or tolyl-dihydrouracil (tDHU), 31 linker diversity was incorporated using mono-N-Boc diamines as the key building ...

2024年8月16日 · In this review, we have covered the discovery and synthesis of the JQ1 molecule. The SAR of the JQ1 analogs will help researchers develop potent JQ1 compounds with improved inhibitory...

2017年2月14日 · BRD4 inhibitor (+)-JQ1 (7, Figure 5) is highly efficacious against NMC tumor growth in xenografted mice. BRD4 can also physically interact with androgen receptor (AR), and disruption of this interaction by a BET inhibitor can abrogate BRD4 localization to AR target loci and AR-mediated gene transcription. Interestingly, BET inhibition was found ...

2024年8月16日 · JQ1: a novel potential therapeutic target. Accumulating evidence supports the notion of BRD4 suppression as a target of therapeutic intervention in clinical oncology and advances the understanding of the role of the JQ1 /BRD4 protein.

We found that MYCN -amplified SCLC cells were highly sensitive to a Bromodomain and Extra-Terminal domain (BET) inhibitor JQ1, which was able to inhibit N-Myc protein expression. The inhibition of N-Myc by JQ1 induced the expression of Bim, and thereby sensitizing MYCN -amplified SCLC cells to ABT-263.

2017年9月21日 · We found that MYCN-amplified SCLC cells were highly sensitive to a Bromodomain and Extra-Terminal domain (BET) inhibitor JQ1, which was able to inhibit N-Myc protein expression. The inhibition of N-Myc by JQ1 induced the expression of Bim, and thereby sensitizing MYCN-amplified SCLC cells to ABT-263. The …

2024年4月1日 · PDT and JQ1 provided a cascading facilitation effect and added strengths and compensates for weaknesses. JQ1, a small molecule inhibitor of BRD4, is superior in synergistic treatment with PDT. The nanocomplex exhibited enhanced immunotherapeutic effects and inhibited distant tumour growth.

利用分子胶SAR范围窄的特点，设计基于CRBN（或其他E3连接酶）的数量巨大的化合物库，再通过表型筛选+蛋白质组学的方法去发现基于新靶点的分子胶降解剂。 达歌生物的技术平台便是采用了类似策略，下图以供参考。 当然采用该策略的不止这一家。 2. 在小分子抑制剂（或靶蛋白小分子亲和配体）的结构基础上，在特定位置引入小的E3连接酶配体的片段，例如CRBN的戊二酰亚胺片段，或是ZFP91的α-Pyr片段（天然产物蟾毒灵便是如此，如下图所示）。 【不是CRBN？ …