Cereblon protein degradation. Small structural changes can have profound impacts on ...
Cereblon protein degradation. Small structural changes can have profound impacts on the overall profile of these compounds, including depth of on-target degradation, neosubstrate degradation selectivity, as well as other drug-like properties Small molecule–triggered protein degradation tags (degrons) are powerful tools to study the effects of the loss of a protein of interest and for target validation. Hear from leading scientists on a range of subjects, including the latest insights into profiling cullin-RING ligases, Degraders as selective chemical tools, bivalent molecular glue Degraders, natural substrate recognition motifs for cereblon, direct-to-biology PROTAC® synthesis . Lenalidomide, along with other thalidomide derivatives, are useful for constructing small molecules for targeted protein degradation and PROTAC (proteolysis-targeting chimeras) technology. However, existing small-molecule approaches require arduous optimization and are largely confined to 5 days ago · Cambridge, UK, 26 February 2026 – Amphista Therapeutics (“the Company” or “Amphista”), a leader in the discovery and development of next generation non-cereblon/VHL targeted protein degradation (TPD) medicines, presented new data at the Keystone Symposia on Proximity Based Biology and Therapeutics: Targeted Protein Degradation and 5 days ago · Cambridge, UK, 26 February 2026 – Amphista Therapeutics (“the Company” or “Amphista”), a leader in the discovery and development of next generation non-cereblon/VHL targeted protein Jan 1, 2026 · Technologies such as cryo-EM, artificial intelligence (AI)-driven modeling, and chemoproteomics are accelerating MG discovery and rational design. Proteins recruited to this degron•small molecule•E3 ligase ternary complex by Jan 20, 2026 · Targeted protein degradation by molecular glue degraders (MGDs) is an emergent therapeutic modality in which small-molecule compounds repurpose the activity of E3 ubiquitin ligases to recruit Jun 20, 2024 · Cereblon (CRBN) is an E3 ligase substrate adapter widely exploited for targeted protein degradation (TPD) strategies. However, achieving efficient and selective target degradation is a preeminent challenge with ligands that engage CRBN. In the presence of a small molecule in mammalian cells, degron tags form a complex with an E3 ubiquitin ligase effector such as cereblon (CRBN). For example, E3 ubiquitin ligases recruit substrate proteins and transfer a ubiquitin tag to target those proteins for destruction by the proteasome. The Nov 22, 2023 · Modulating the chemical composition of cereblon (CRBN) binders is a critical step in the optimization process of protein degraders that seek to hijack the function of this E3 ligase. Many cellular processes and pathways are mediated by the regulation of protein–protein complexes. Aug 20, 2025 · Targeted protein degradation (TPD) is a rapidly emerging drug discovery paradigm that relies on engagement of normal cellular proteolytic processes to degrade disease-associated proteins 1. Key breakthroughs include cereblon (CRBN)-binding MGs, which have enabled targeted protein degradation and spurred a wave of clinical trials. We will delve into the core mechanisms, provide detailed experimental protocols for key assays, and present a quantitative analysis of prominent Cereblon-targeting compounds. Feb 24, 2026 · Targeted protein degradation (TPD) has enabled modulation of previously undruggable proteins. Cereblon E3 ligase modulators (CELMoDs) promote cereblon (CRBN)–mediated ubiquitination and proteasomal degradation of IKZF1 (Ikaros) and IKZF3 (Aiolos), resulting in suppression of the IRF4–MYC survival axis in multiple myeloma (MM) plasma cells and induction of tumor- intrinsic cytotoxicity. Here, we report that the cyclimids, ligands derived from the C-terminal cyclic imide degrons of CRBN, exhibit distinct modes of interaction with CRBN and offer This technical guide provides a comprehensive overview of Cereblon (CRBN)-mediated protein degradation, a revolutionary therapeutic modality with significant implications for drug discovery and development. Lenalidomide is a ligand demonstrated to bind the Cereblon (CRBN) protein. Our 3rd Targeted Protein Degradation Symposium covered some of the hottest science from this exciting field and included talks on antiviral PROTACs, a clinical candidate Degrader of BRD9, the BromoTag ® degradation platform, degraders targeting the CBP/p300 lysine acetyltransferases, new cereblon-recruiting warheads for PROTAC ® design and 13 hours ago · Thalidomide analogues have demonstrated therapeutic efficacy in haematologic neoplasms, by binding to cereblon (CRBN; the substrate binding component of the E3 protein ligase complex DDB1/CUL4A Our free Targeted Protein Degradation Symposium covers new developments at the cutting edge of this exciting field. omqhpmkcalznllvxrgwhvrwklzfuusswesvprglifzlle