用于靶向蛋白降解的全套解决方案
What is Induced Proximity?
Induced Proximity is an approach that employs two ligands covalently joined by a linker, to bring two proteins, a target protein of interest (POI) and an effector, into close proximity. The induced proximity of POI and effector leads to an alteration to the POI, triggering a biological response. The POI can undergo a variety of changes including post-translational modification, degradation, autophagy, stabilization, dimerization, and cellular shuttling.
Targeted protein degradation utilizes heterobifunctional small molecule Degraders (e.g. PROTAC® molecules, SNIPERs etc) to bind the POI and recruits an E3 ligase to form a ternary complex. This initiates the ubiquitination of the POI and its subsequent destruction by the proteasome. There are a number of significant benefits to using this technology. Efficient and highly selective protein knock-down can be achieved both in vitro and in vivo. Degraders act catalytically by repeatedly engaging and directing the ubiquitination of the POI and can therefore be used at very low doses to achieve sustained knock-down.
Bio-Techne 为靶向蛋白降解研发提供全套产品和服务。我们的工具将帮助您探索和验证您的目的靶标、开发新型蛋白降解剂分子并研究其活性以及构建您自己的降解分析法。我们的产品包括：小分子蛋白质降解剂（例如 PROTAC® 降解剂）；aTAG、dTAG 和 BromoTag® 降解剂及定制 TAG 敲入细胞系；降解剂构建模块、泛素-蛋白酶体系统蛋白与分析法；分析靶向蛋白降解和定制降解剂服务。
靶向蛋白降解的产品和服务
靶标验证和探索
靶标验证，即确定潜在分子靶标参与生理功能或疾病进程的过程，是开发新降解剂、药物发现和生物研究的关键步骤。我们的 TAG 降解平台提供了一种差异化的靶标验证方法，它使用靶向蛋白降解可逆地敲减潜在蛋白质靶标并使得探索下游表型成为可能。
降解剂设计和合成
可使用 PROTAC 分子等小分子蛋白质降解剂实现靶向蛋白降解。Bio-Techne 提供成套产品和服务来支持您的降解剂设计和合成项目并且省时省经费，包括我们的 PROTAC Panel Builder在线工具；庞大的现成的降解剂构建模块；以及用于发现新 E3 连接酶配体的工具。
用于靶向蛋白降解的分析方法
成功开发小分子蛋白降解剂需要经过一系列分析，以确定降解剂活性。分析工作流程应包括：降解剂诱导的靶标接合作用和三元复合物形成；靶蛋白泛素化；以及靶标降解及其下游影响。多次正交分析将最大限度提高成功开发降解剂的机会。
E3 连接酶和泛素-蛋白酶体系统
Bio-Techne 通过旗下品牌 R&D SystemsTM 提供种类广泛的产品，帮助您探索和表征泛素生物学。正在快速扩大的产品组合包括高活性 E3 泛素连接酶（包括 SKP2、VHL、Cereblon (CRBN) 和 DCAF 蛋白）及分析试剂盒和组分，以及 抗体。我们还提供 Cullin-Rbx 复合物（包括 NEDD 化 cullin），后者可以与您纯化的底物结合性复合物偶联，以生成活性连接酶。
靶向蛋白降解的定制服务
Bio-Techne 提供独特的定制服务产品组合，以支持您的 PROTAC® 开发及靶标验证项目。利用我们的定制化学专业知识开发活性降解剂，以敲减您选择的靶标或定制构建模块。我们还提供 E3 连接酶开发定制服务，协助您进行泛素化分析，及定制敲入细胞系，这些细胞系将您的目的靶蛋白表达为含“TAG”的融合蛋白，以便用于 TAG 降解平台。
靶向蛋白降解资源
5th Virtual Bio-Techne TPD and Induced Proximity Symposium
5th Virtual Bio-Techne TPD and Induced Proximity Symposium
Our 5th virtual symposium covered new developments from the leading scientists working in induced proximity research. Topics covered include: transcriptional kinases to activate apoptosis, degradation of BRD9 by a novel “targeted glue”, discovery of protein degraders and stabilizers, mechanisms of degrader-targeted protein ubiquitinability, and degraders of HIV-1 Nef for antiretroviral drug development.
Scientific Review: Simple Western Hits the Bullseye of TPD
Scientific Review: Simple Western Hits the Bullseye of TPD
This review highlights vital publications that represent Simple Western’s high-throughput screening of degrader activity with reproducible quantification, flexible multiplex strategies, and fast time to results, from drug discovery of novel degraders through translation to the clinic.
视频：什么是靶向蛋白降解？
视频：什么是靶向蛋白降解？
This short animation explains the fundamentals of Targeted Protein Degradation (TPD) using small molecule Protein Degraders or PROTACs, that harness the ubiquitin-proteasome system to selectively remove proteins from cell.
网络研讨会：PROTAC® 降解剂开发解决方案
网络研讨会：PROTAC® 降解剂开发解决方案
最初在 Cell Bio 2020 年网络会议上，由我们的创新部经理 Hannah Maple 博士作为技术讲座演讲，这场网络研讨会介绍了 Bio-Techne 的全面解决方案支持您的降解剂研发项目。
Background Information
How do Degrader molecules work?
Targeted Protein Degradation is a technique that uses heterobifunctional small molecule Degraders to bring about efficient and highly selective degradation of a target protein of interest. Targeted protein degradation enables investigation of the downstream consequences of protein knockdown and provides an easy-to-use method for target validation.
Bio-Techne provides small molecule Protein Degraders, including PROTAC (PROteloysis TArgeting Chimera) molecules and TAG Degraders (dTAG/aTAG/BromoTag). PROTAC molecules comprise a ligand that binds a target of interest joined by a linker to an E3 ligase ligand. A ternary complex is formed by the simultaneous binding of the Degrader to the target protein and the E3 ligase, which initiates ubiquitination of the target protein and its subsequent destruction by the proteasome. TAG Degraders work on a similar principle, but comprise an E3 ligase ligand linked to a compound that binds a fusion of a TAG degron with a target protein of interest. Degraders enable the knockdown of proteins for which there are no known ligands, enabling targeting of previously undruggable targets.
Bio-Techne supplies a range of other products and services to support Targeted Protein Degradation studies, including Degrader Building Blocks to enable you to create your own Degraders, as well as Ubiquitin-Proteasome System (UPS) Proteins and Assays, Assays for Protein Degradation, and Custom Degraders Services.
为何使用降解剂？
小分子降解剂在靶蛋白敲减方面提供胜过基因调控的几个优势：
- 降解剂有细胞渗透性，适合体内和体外使用，可直接应用于细胞，无需转染或表达载体。
- 它们适用于多种细胞系，不要求细胞易于转染。
- 效果持续时间根据化合物洗脱情况可调整、可逆。
- 具有反复作用并引导靶分子泛素化的催化性作用模式，从而允许以亚化学计量浓度使用。
PROTAC® 是 Arvinas Operations, Inc. 的注册商标，经许可使用。
BromoTag® 是邓迪大学的注册商标，经许可使用。