{"id":6828,"date":"2025-12-09T09:55:54","date_gmt":"2025-12-09T09:55:54","guid":{"rendered":"https:\/\/www.sygnaturediscovery.com\/?post_type=case-study&#038;p=6828"},"modified":"2026-02-02T18:03:24","modified_gmt":"2026-02-02T18:03:24","slug":"cereblon-crystallography-with-crbn-midi-accelerating-molecular-glue-and-protac-discovery","status":"publish","type":"case-study","link":"https:\/\/www.sygnaturediscovery.com\/fr\/case-study\/cereblon-crystallography-with-crbn-midi-accelerating-molecular-glue-and-protac-discovery\/","title":{"rendered":"Cereblon Crystallography with CRBN-midi: Accelerating Molecular Glue and PROTAC Discovery"},"content":{"rendered":"\n<h2 class=\"wp-block-heading has-dark-blue-500-color has-text-color has-link-color has-text-3-xl-font-size wp-elements-5ecd02789004f712f0313d6bea2c3992\">Our latest achievement: the successful expression, purification, and crystallization of Cereblon-midi (CRBN-midi) reinforces Sygnature Discovery\u2019s position at the forefront of the rapidly expanding targeted protein degradation (TPD) landscape.<\/h2>\n\n\n\n<h2 class=\"wp-block-heading has-dark-blue-500-color has-text-color has-link-color has-text-2-xl-font-size wp-elements-3f516fc619817c4fe92be40a3b1665a9\">Transforming Drug Discovery<\/h2>\n\n\n\n<p>Targeted protein degradation is redefining how scientists approach diseases once considered \u201cundruggable.\u201d Instead of simply blocking the activity of proteins, TPD strategies harness the cell\u2019s own machinery to eliminate them, unlocking new possibilities for next-generation therapeutics.<\/p>\n\n\n\n<p>At the heart of many TPD systems is Cereblon (CRBN), a key component of an E3 ubiquitin ligase complex. Acting as a \u201cmolecular matchmaker,\u201d CRBN enables degraders to engage non-native targets effectively by bridging target interactions via PROTACs and molecular glues. However, studying CRBN has been challenging due to its dependence on DDB1 for structural stability. Thanks to the development of the CRBN-midi construct, we can now resolve this challenge with remarkable accuracy and confidence.<\/p>\n\n\n\n<h2 class=\"wp-block-heading has-dark-blue-500-color has-text-color has-link-color has-text-2-xl-font-size wp-elements-f58a9a6d5825054406de3f3d0909821f\">The CRBN-Midi Advantage<\/h2>\n\n\n\n<p>First introduced by Kroupova et al., the engineered CRBN-midi format preserves CRBN\u2019s functional core while improving stability, solubility, and suitability for structural biology. This construct facilitates X-ray crystallography, enabling structure-based screens and designs for therapeutic applications.<\/p>\n\n\n\n<p>At Sygnature Discovery, we\u2019ve harnessed this design to offer a robust, ready-to-use CRBN-midi system empowering clients to accelerate TPD research with reliable biochemical and biophysical assays. Using the published CRBN-Midi construct, we have enabled an off-the-shelf crystallization system and complementary ligand binding analysis by SPR.<\/p>\n\n\n\n<h2 class=\"wp-block-heading has-dark-blue-500-color has-text-color has-link-color has-text-2-xl-font-size wp-elements-a0e9b2548d5644291cf8b457d0f4a077\">Two Structures, One Breakthrough Platform<\/h2>\n\n\n\n<p>Using crystallization conditions similar to those previously reported, followed by X-ray diffraction techniques, we\u2019ve determined high-resolution CRBN-midi structures that can provide valuable insight into CRBN\u2019s binding behavior:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Apo CRBN-midi (3.2 \u00c5 Resolution): Reveals the apo conformation of CRBN-midi, forming the baseline for ligand-induced structural changes.<\/li>\n\n\n\n<li>CRBN-midi\u2013Lenalidomide Complex (1.96 \u00c5 Resolution): Highlights molecular interactions critical for degrader design and optimization.<\/li>\n<\/ul>\n\n\n\n<figure class=\"wp-block-image size-full is-style-rounded is-style-rounded--1\"><img loading=\"lazy\" decoding=\"async\" width=\"780\" height=\"491\" src=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/SEC-and-PAGE-of-CRBN-midi-1.webp\" alt=\"\" class=\"wp-image-6821\" srcset=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/SEC-and-PAGE-of-CRBN-midi-1.webp 780w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/SEC-and-PAGE-of-CRBN-midi-1-300x189.webp 300w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/SEC-and-PAGE-of-CRBN-midi-1-768x483.webp 768w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/SEC-and-PAGE-of-CRBN-midi-1-572x360.webp 572w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/SEC-and-PAGE-of-CRBN-midi-1-640x403.webp 640w\" sizes=\"(max-width: 780px) 100vw, 780px\"><figcaption class=\"wp-element-caption\"><em><strong>Figure 1:<\/strong> Size exclusion chromatography and SDS-PAGE data showing purity of CRBN-midi <\/em><\/figcaption><\/figure>\n\n\n\n<figure class=\"wp-block-image size-medium\"><img loading=\"lazy\" decoding=\"async\" width=\"300\" height=\"253\" src=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/Crystal-Structure-of-CRBN-midi-in-Apo-form-300x253.webp\" alt=\"\" class=\"wp-image-6822\" srcset=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/Crystal-Structure-of-CRBN-midi-in-Apo-form-300x253.webp 300w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/Crystal-Structure-of-CRBN-midi-in-Apo-form-768x647.webp 768w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/Crystal-Structure-of-CRBN-midi-in-Apo-form-427x360.webp 427w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/Crystal-Structure-of-CRBN-midi-in-Apo-form-640x540.webp 640w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/Crystal-Structure-of-CRBN-midi-in-Apo-form.webp 873w\" sizes=\"(max-width: 300px) 100vw, 300px\"><figcaption class=\"wp-element-caption\"><em><strong>Figure 2. <\/strong>Crystal structures of CRBN-midi in Apo form<\/em> <\/figcaption><\/figure>\n\n\n\n<figure class=\"wp-block-image size-medium\"><img loading=\"lazy\" decoding=\"async\" width=\"300\" height=\"274\" src=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/Crystal-Structure-of-CRBN-midi-with-Lenalidomide-300x274.webp\" alt=\"\" class=\"wp-image-6823\" srcset=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/Crystal-Structure-of-CRBN-midi-with-Lenalidomide-300x274.webp 300w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/Crystal-Structure-of-CRBN-midi-with-Lenalidomide-393x360.webp 393w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/Crystal-Structure-of-CRBN-midi-with-Lenalidomide.webp 611w\" sizes=\"(max-width: 300px) 100vw, 300px\"><figcaption class=\"wp-element-caption\"><em><strong>Figure 3.<\/strong>  a) Crystal structure of CRBN-midi in complex with Lenalidomide <\/em><\/figcaption><\/figure>\n\n\n\n<figure class=\"wp-block-image size-medium\"><img loading=\"lazy\" decoding=\"async\" width=\"300\" height=\"191\" src=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/CRBN-midi-electron-density-map-of-Lenalidomide-300x191.webp\" alt=\"\" class=\"wp-image-6824\" srcset=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/CRBN-midi-electron-density-map-of-Lenalidomide-300x191.webp 300w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/CRBN-midi-electron-density-map-of-Lenalidomide-567x360.webp 567w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/CRBN-midi-electron-density-map-of-Lenalidomide.webp 625w\" sizes=\"(max-width: 300px) 100vw, 300px\"><figcaption class=\"wp-element-caption\"><em><strong>Figure 3.<\/strong> b) Electron density map of Lenalidomide (yellow), 2mFo-DFc map contoured at 1\u03c3, grey<\/em><\/figcaption><\/figure>\n\n\n\n<h2 class=\"wp-block-heading has-dark-blue-500-color has-text-color has-link-color has-text-2-xl-font-size wp-elements-6043b7cc628a62927f34407bc22d6dca\">Active and Ready: CRBN-midi Binding Confirmed via SPR<\/h2>\n\n\n\n<p>We\u2019ve enabled ligand-binding analysis with CRBN-midi using SPR. Using immobilized CRBN-midi on the sensor surface, we demonstrate saturable binding of lenalidomide.<\/p>\n\n\n\n<figure class=\"wp-block-image size-full is-style-rounded is-style-rounded--2\"><img loading=\"lazy\" decoding=\"async\" width=\"921\" height=\"329\" src=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/Binding-of-lenalidomide-to-CRBN-midi-by-SPR.webp\" alt=\"\" class=\"wp-image-6825\" srcset=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/Binding-of-lenalidomide-to-CRBN-midi-by-SPR.webp 921w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/Binding-of-lenalidomide-to-CRBN-midi-by-SPR-300x107.webp 300w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/Binding-of-lenalidomide-to-CRBN-midi-by-SPR-768x274.webp 768w, https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/12\/Binding-of-lenalidomide-to-CRBN-midi-by-SPR-640x229.webp 640w\" sizes=\"(max-width: 921px) 100vw, 921px\"><figcaption class=\"wp-element-caption\"><em><strong>Figure 4. <\/strong>Binding of lenalidomide to CRBN-midi by SPR: Saturable binding is observed between lenalidomide and immobilized CRBN-midi.<\/em><\/figcaption><\/figure>\n\n\n\n<h2 class=\"wp-block-heading has-dark-blue-500-color has-text-color has-link-color has-text-2-xl-font-size wp-elements-44d4bbf75a070d1194b9a56a282184ed\">Flexible solutions for degrader design<\/h2>\n\n\n\n<p>We now have a complete toolbox to support the design of degraders. The CRBN-midi described here performs well in binary assays, particularly for imids, and is an excellent tool for structure-guided design of new glues and Protacs.\u00a0 This complements our offer with the full a <a href=\"https:\/\/www.sygnaturediscovery.com\/case-study\/cereblon-purification-and-spr\/\" target=\"_blank\" rel=\"noreferrer noopener\">DDB1\/Cereblon complex<\/a> which performs better in ternary assays, and highlights our deep expertise in the degrader space, delivering high-quality data for complex programs.<\/p>\n\n\n\n<h2 class=\"wp-block-heading has-dark-blue-500-color has-text-color has-link-color has-text-2-xl-font-size wp-elements-347716b2c128062415609c90b636e9d5\">Integrated Structural Biology and Biophysical Expertise<\/h2>\n\n\n\n<p>Sygnature Discovery offers a fully integrated workflow to support partners at every stage of discovery:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Protein Expression and Purification: Optimized systems for challenging targets<\/li>\n\n\n\n<li>Compound Screening: To identify binders for molecular glue and PROTAC programs<\/li>\n\n\n\n<li>Crystallization and X-ray Structure Determination: Industry-leading resolution and reliability<\/li>\n\n\n\n<li>Molecular Glue Characterization: From binding assays to structural and biophysical analysis<\/li>\n<\/ul>\n\n\n\n<p>Our technical depth, flexibility, and scientific insight deliver structural data that drives informed decisions and accelerates timelines.<\/p>\n\n\n\n<h2 class=\"wp-block-heading has-dark-blue-500-color has-text-color has-link-color has-text-2-xl-font-size wp-elements-a93d55e724c79e6d86de5908b8b99178\">Empowering Discovery for Our Partners<\/h2>\n\n\n\n<p>Our progress with CRBN-midi does more than deliver faster structural insights, it strengthens CHARMED , Sygnature\u2019s pioneering discovery platform. By integrating these learnings, we expand CHARMED\u2019s ability to accelerate molecular glue and degrader programs for biotech and pharmaceutical innovators.<\/p>\n\n\n\n<p>Contact us today\u00a0 to learn how our structural biology and ligand screening services can accelerate your next breakthrough.<\/p>\n\n\n\n<p><\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"featured_media":0,"template":"","category":[686,680,702,704,743],"resource_tag":[],"class_list":["post-6828","case-study","type-case-study","status-publish","hentry","category-modalities","category-protein-and-structure","category-protein-expression-and-purification","category-structural-biology","category-tpd"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.4 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Cereblon Crystallography with CRBN-midi: Accelerating Molecular Glue and PROTAC Discovery - Sygnature<\/title>\n<meta name=\"description\" content=\"Our latest achievement: the successful expression, purification, and crystallization of Cereblon-midi (CRBN-midi) reinforces Sygnature Discovery\u2019s position at the forefront of the rapidly expanding targeted protein degradation (TPD) landscape.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.sygnaturediscovery.com\/fr\/case-study\/cereblon-crystallography-with-crbn-midi-accelerating-molecular-glue-and-protac-discovery\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Cereblon Crystallography with CRBN-midi: Accelerating Molecular Glue and PROTAC Discovery - 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