{"database":"Pride","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Txt":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/05/PXD075518/checksum.txt"],"Raw":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/05/PXD075518/20260114_003_S1084459_Z_DMSO_3_Z_DMSO.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/05/PXD075518/20260114_009_S1084457_Z_DMSO_1_Z_DMSO.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/05/PXD075518/20260114_016_S1084454_E_DMSO_1_E_DMSO.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/05/PXD075518/20260114_005_S1084456_E_DMSO_3_E_DMSO.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/05/PXD075518/20260114_018_S1084458_Z_DMSO_2_Z_DMSO.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/05/PXD075518/20260114_011_S1084455_E_DMSO_2_E_DMSO.raw"],"Other":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/05/PXD075518/DIANN.zip"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"labhead_mail":["katharina.gapp@hest.ethz.ch"],"submitter":["Robin Scheuplein"],"technology_type":["Mass Spectrometry","Data-independent acquisition"],"software":["Not available"],"submitter_keywords":[""],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD075518"],"tissue":["Permanent Cell Line Cell","Cell Culture"],"sample_protocol":["The samples dissolved in RIPA lysis buffer were boiled at 95°C for 10 minutes and treated with High Intensity Focused Ultrasound (HIFU) for 1 minute before centrifugation at 20000 x g for 10 min. Protein concentration was determined using the Lunatic UV/Vis polychromatic spectrophotometer (Unchained Labs).For each sample 25 µg of protein were taken and reduced with 5 mM TCEP(tris(2-carboxyethyl)phosphine) and alkylated with 15 mM chloroacetamide at 30°C for 30 min.Samples were processed using the single‐pot solid‐phase enhanced sample preparation (SP3). The SP3 protein purification, digest and peptide clean-up was performed using a KingFisher Flex System (Thermo Fisher Scientific) and Carboxylate-Modified Magnetic Particles (GE Life Sciences; GE65152105050250, GE45152105050250). Beads were conditioned following the manufacturer’s instructions, consisting of 3 washes with water at a concentration of 1 µg/µl. Samples were diluted with 100% ethanol to a final concentration of 60% ethanol. The beads, wash solutions and samples were loaded into 96 deep well- or micro-plates and transferred to the KingFisher.  Following steps were carried out on the robot: collection of beads from the last wash, protein binding to beads, washing of beads in wash solutions 1-3 (80% ethanol), protein digestion (overnight at 37°C with a trypsin:protein ratio of 1:50 in 50 mM Triethylammoniumbicarbonat (TEAB)) and peptide elution from the magnetic beads using MilliQ water. The digest solution and water elution were combined and dried to completeness and re-solubilized in 20 µL of MS sample buffer (3% acetonitrile, 0.1% formic acid).Mass spectrometry analysis was performed on an Orbitrap Exploris 480 mass spectrometer (Thermo Fisher Scientific) equipped with a Nanospray Flex Ion Source (Thermo Fisher Scientific) and coupled to an M-Class UPLC (Waters). Solvent composition at the two channels was 0.1% formic acid for channel A and 0.1% formic acid, 99.9% acetonitrile for channel B. Column temperature was 50°C. For each sample 200 Abs of peptides were loaded on a commercial nanoEase  MZ Symmetry C18 Trap Column (100Å, 5 µm, 180 µm x 20 mm, Waters) followed by a nanoEase MZ C18 HSS T3 Column (100Å, 1.8 µm, 75 µm x 250 mm, Waters). The peptides were eluted at a flow rate of 300 nL/min. After a 3 min initial hold at 5% B, a gradient from 5 to 22 % B in 80 min and 22 to 32% B in additional 10 min was applied. The column was cleaned after the run by increasing to 95 % B and holding 95 % B for 10 min prior to re-establishing loading condition for another 10 minutes. For the analysis of the individual samples, the mass spectrometer was operated in data-independent mode (DIA). DIA scans covered a range from 400 to 960 m/z in windows of 8 m/z. The resolution of the DIA windows was set to 30’000, with a normalized AGC target value of 1’000%, the maximum injection time set to auto and a fixed normalized collision energy (NCE) of 30 %. Each instrument cycle was completed by a full MS scan monitoring 396 to 1’000 m/z at a resolution of 60’000. The mass spectrometry proteomics data were handled using the local laboratory information management system (LIMS)."],"repository":["Pride"],"modification":[""],"quantification_method":[""],"data_protocol":["The acquired MS data were processed for identification and quantification using DIANN v1.9. Spectra were searched using the Uniprot human database in FASTA file format (1 sequence per gene), and common protein contaminants. Carbamidomethylation of cysteine was fixed modifications, while methionine oxidation was variable. Enzyme specificity was set to trypsin/P, allowing a minimal peptide length of 7 amino acids and a maximum of two missed cleavages.The R package prolfqua was used to analyze the differential expression and to determine group differences, confidence intervals, and false discovery rates for all quantifiable proteins. The protein lists were filtered with a threshold of 1 log2FC and an FDR of 0.05%. The analysis was run on the local computing infrastructure."],"omics_type":["Proteomics"],"labhead":["Prof. Dr."],"instrument_platform":[""],"labhead_affiliation":["Department of Health Sciences and Technology (D-HEST) Institute Neurosciences, ETH Zurich"],"species":["Homo Sapiens (human)"],"submission_type":["PARTIAL"],"publication":["Not available"],"submitter_mail":["robin.scheuplein@gmail.com"],"submitter_affiliation":["Laboratory of Epigenetics and Neuroendocrinology, Institute for Neuroscience, Department of Health Science and Technology, ETH Zürich, Zürich 8057, Switzerland\nNeuroscience Center Zürich, ETH Zürich and University of Zürich, Zürich 8057, Switzerland"],"submitter_country":["Switzerland"],"additional_accession":[]},"is_claimable":false,"name":"Light-Controlled Disruption of Cancer Cell Dormancy via Photoswitchable Stress Hormone Receptor Degraders","description":"Cancer cell dormancy is a key contributor to therapy resistance and disease relapse. The glucocorticoid receptor (GR), a major mediator of stress hormone signaling, has emerged as a central regulator of dormancy in non-lymphoid solid tumors, particularly lung cancer. However, systemic GR inhibition or degradation using conventional Proteolysis Targeting Chimeras (PROTACs) risks widespread on-target toxicity due to their constitutive activity. We hypothesized that integrating photoswitchable elements into PROTACs, termed photoPROTACs, would enable wavelength-specific, spatiotemporally precise modulation of GR degradation and dormancy-associated signaling pathways.  Here, we synthesized a diverse series of photoPROTACs incorporating photoswitchable arylazotriazole or arylazopyrazole scaffolds, including previously unreported (OEt)2- and (NMe2)2-substituted photoswitches. Arylazopyrazole-based GR photoPROTACs bearing Me2- and (OEt)2 substituents exhibited near-quantitative photoisomerization (95% Z-isomer; 89% – 92% E-isomer), no photobleaching, and thermal half-lives in the range of 3−12.2 days in DMSO. Among them, KH-5-306 and KH-5-309 induced potent, specific, and reversible GR degradation in their thermodynamically stable E-isomeric form at low nanomolar concentrations, with markedly reduced activity in the Z-isomeric state. Transcriptomic profiling showed that E-KH-5-309 disrupts GR-driven dormancy-associated gene expression programs in a non-small lung cancer (NSLC) model, while the Z-isomer remains functionally inert. Our findings establish a framework for the rational design of photoswitchable PROTACs beyond GR and demonstrate their potential to achieve spatiotemporal control of stress hormone receptor signaling, enabling mechanistic insights into GR function and the targeted disruption of cancer cell dormancy.","dates":{"publication":"2026-05-21","submission":"2026-03-11"},"accession":"PXD075518","cross_references":{"TAXONOMY":["NEWT:6945","NEWT:3555","NEWT:241368","NEWT:2","NEWT:157546","NEWT:190802","NEWT:35554","NEWT:150475","NEWT:9417","NEWT:347515","NEWT:1216979","NEWT:307972","NEWT:544496","NEWT:5180","NEWT:256737","NEWT:115104","NEWT:1081927","NEWT:67825","NEWT:13076","NEWT:1249668","NEWT:317","NEWT:1736309","NEWT:7227","NEWT:7469","NEWT:885318","NEWT:4081","NEWT:876138","NEWT:554","NEWT:98334","NEWT:237561","NEWT:10036","NEWT:7574","NEWT:1351","NEWT:7215","NEWT:272563","NEWT:507601","NCBITaxon:79857","NCBITaxon:6157","NEWT:95648","NEWT:746360","NEWT:6239","NEWT:1589","NEWT:470150","NEWT:135622","NEWT:216257","NEWT:6915","NEWT:9986","NEWT:101510","NEWT:4054","NEWT:3880","NEWT:8782","NEWT:1000589","NEWT:1902","NEWT:85962","NEWT:160488","NEWT:28104","NEWT:317447","NEWT:7955","NCBITaxon:2","NEWT:985076","NEWT:7959","NEWT:2261","NEWT:4565","NEWT:1264690","NEWT:6192","NEWT:28532","NCBITaxon:38727","NEWT:34305","NEWT:59729","NCBITaxon:183674","NEWT:224308","NEWT:626528","NEWT:139927","NEWT:4558","NEWT:209285","NEWT:216595","NEWT:243230","NEWT:8355","NEWT:931281","NEWT:7029","NEWT:1283300","NEWT:334747","NCBITaxon:79824","NCBITaxon:4563","NEWT:5755","NEWT:3218","NEWT:5759","NEWT:1736231","NEWT:436486","NEWT:6287","NEWT:2242","NEWT:300641","NEWT:4784","NEWT:727","NEWT:9796","NEWT:725","NEWT:360106","NEWT:260707","NEWT:287","NEWT:10117","NEWT:10239","NEWT:10116","NEWT:1280","NEWT:1836","NEWT:1735272","NEWT:83334","NEWT:83332","NEWT:29760","NEWT:703612","NEWT:260705","NEWT:80863","NEWT:2697049","NEWT:1148","NEWT:11676","NEWT:55571","NEWT:100226","NCBITaxon:6073","NEWT:4530","NEWT:4896","NEWT:6279","NEWT:7370","NEWT:6282","NEWT:1134506","NEWT:575584","NEWT:1773","NEWT:38783","NEWT:8727","NEWT:1895","NEWT:1182590","NEWT:8726","NEWT:10090","NEWT:935293","NEWT:749200","NEWT:4120","NEWT:5693","NEWT:8724","NEWT:51511","NEWT:92867","NEWT:8723","NEWT:990346","NEWT:5334","NEWT:145953","NEWT:257309","NEWT:230741","NEWT:284812","NCBITaxon:10359","NCBITaxon:1313","NEWT:43330","NEWT:242619","NEWT:44544","NEWT:373995","NEWT:544404","NEWT:3702","NEWT:129249","NEWT:8839","NEWT:4232","NEWT:990119","NEWT:4113","NEWT:11298","NEWT:171101","NEWT:196627","NEWT:408172","NEWT:5691","NEWT:408170","NEWT:493760","NEWT:260710","NEWT:627025","NEWT:400772","NEWT:1097677","NEWT:3708","NEWT:106592","NEWT:9913","NEWT:1432138","NEWT:10312","NEWT:4100","NEWT:1076","NEWT:6763","NEWT:803","NEWT:8030","NEWT:29722","NEWT:380394","NEWT:1692259","NEWT:1639","NEWT:188229","NEWT:3818","NEWT:480","NEWT:4909","NEWT:67767","NEWT:135588","NEWT:1843183","NEWT:95486","NEWT:58002","NEWT:9103","NEWT:4577","NEWT:5664","NEWT:2157","NEWT:146479","NEWT:10306","NEWT:1911079","NEWT:145943","NEWT:3635","NEWT:5811","NEWT:235443","NEWT:1480154","NEWT:1274414","NEWT:3197","NEWT:9615","NEWT:10299","NEWT:860688","NEWT:884019","NEWT:169963","NEWT:36329","NEWT:9606","NEWT:367830","NEWT:157295","NEWT:410289","NEWT:373153","NEWT:915099","NEWT:74940","NEWT:1450511","NEWT:470","NEWT:84023","NEWT:9838","NCBITaxon:9615","NEWT:1193501","NEWT:3055","NEWT:6326","NEWT:6689","NEWT:2762","NEWT:5476","NEWT:1174673","NEWT:562","NEWT:1274432","NEWT:1274426","NEWT:1423","NEWT:4932","NEWT:70448","NEWT:9825","NEWT:1274423","NEWT:3603","NEWT:698936","NEWT:2759","NEWT:3847","NEWT:39946","NEWT:9823","NEWT:9940","NEWT:573","NEWT:9031","NEWT:1274420","NEWT:7091"],"ORCID":["0009-0000-8897-5408"]}}