Selected Publications of BIGS DrugS
BIGS DrugS PhD students and their supervisors have successfully published their research results. Congratulations!
2024
Holze J, Lauber F, Soler S, Kostenis E, Weindl G. Label-free biosensor assay decodes the dynamics of Toll-like receptor signaling; Nat com.15, 9554 (2024)
Oneto A, Al Hamwi G, Schäkel L, Krüger N, Sylvester K, Petry M, Shamleh RA, Pillaiyar T, Claff T, Schiedel AC, Sträter N, Gütschow M, Müller CE; Nonpeptidic Irreversible Inhibitors of SARS-CoV-2 Main Protease with Potent Antiviral Activity; J. Med. Chem. 2024, 67, 14986-15011.
Brands J, Bravo S, Jürgenliemke L, Grätz L, Schihada H, Frechen F, Alenfelder J, Pfeil C, Ohse PG, Hiratsuka S, Kawakami K, Schmacke LC, Heycke N, Inoue A, König G, Pfeifer A, Wachten D, Schulte G, Steinmetzer T, Watts VJ, Gomeza J, Simon K, Kostenis E; A molecular mechanism to diversify Ca2+ signaling downstream of Gs protein-coupled receptors; Nat Commun. 2024 Sep 3;15(1):7684. doi: 10.1038/s41467-024-51991-6. PMID:39227390.
Kostenis E, Jürgenliemke L, Alenfelder J; G protein-mediated signal transduction: a molecular choreography of G protein activation after GTP binding; Signal. Transduct. Target. Ther. 2024, 9(1), 188.
Hanke W, Alenfelder J, Liu J, Gutbrod P, Kehraus, Crüsemann M, Dörmann P, Kostenis E, Scholz M, König GM; The Bacterial Gq Signal Transduction Inhibitor FR900359 Impairs Soil-Associated Nematodes; J. Chem. Ecol, 2023, 49(9-10):549-569, doi:10.1007/s10886-023-01442-1.
Seidinger A, Roberts R, Bai Y, Müller M, Pfeil E, Matthey M, Rieck S, Alenfelder J, König GM, Pfeifer A, Kostenis E, Klinke A, Fleischmann BK, Wenzel D; Pharmacological Gq inhibition induces strong pulmonary vasorelaxation and reverses pulmonary hypertension. EMBO Mol. Med. 2024 16(8):1930-1956. doi: 10.1038/s44321-024-00096-0.
Sievers J, Voget R, Lu F, Garchitorena KM, Ng YLD, Chau CH, Steinebach C, Figg WD, Krönke J, Gütschow M; Revisiting the Antiangiogenic Mechanisms of Fluorinated Thalidomide Derivatives; Bioorg. Med. Chem. Lett. 2024, 110, 129858.
Barton BE, Collins MK, Chau CH, Choo-Wosoba H, Venzon DJ, Steinebach C, Garchitorena KM, Shah B, Sarin EL, Gütschow M, Figg WD; Preclinical Evaluation of a Novel Series of Polyfluorinated Thalidomide Analogs in Drug Resistant Multiple Myeloma; Biomolecules, 2024, 14, 725
Bricelj A, Ng YLD, Gobec M, Kuchta R, Hu W, Javornik Š, Rožič M, Gütschow M, Zheng G, Krönke J, Steinebach C, Sosič I; Design, Synthesis, and Evaluation of BCL-2 Targeting PROTACs; Chem. Eur. J. 2024, e202400430
Breidenbach J, Voget R, Si Y , Hingst A, Claff T, Sylvester K, Wolf V, Krasniqi V, Useini A, Sträter N, Ogura Y, Kawaguchi A, Müller CE, Gütschow M; Macrocyclic Azapeptide Nitriles: Structure-Based Discovery of Potent SARS-CoV-2 Main Protease Inhibitors as Antiviral Drugs; J. Med. Chem. 2024, 67, 8757-8790
Günther M, Schuler M, Hentschel L, Salm H, Schmitz MT, Jaehde U; Medication Risks and Their Association with Patient-Reported Outcomes in Inpatients with Cancer. Cancers
Zhai S, Schäker-Hübner L, Hanl M, Jacobi L, Pieńkowska DE, Gerhartz J, Voget R, Gütschow, M, Meissner F, Nowak RP, Steinebach C, Hansen FK; Development and characterization of the first selective class IIb histone deacetylase degraders. ChemRxiv 2024. doi: 10.26434/chemrxiv-2024-ngppg.
Scheuerer S, Motlova L, Schäker-Hübner L, Sellmer A, Feller F, Ertl FJ, Koch P, Hansen FK, Barinka C, Mahboobi S; Biological and structural investigation of tetrahydro-β-carboline-based selective HDAC6 inhibitors with improved stability. Eur J Med Chem 2024:116676. doi: 10.1016/j.ejmech.2024.116676.
Kraft FB, Biermann L, Schäker-Hübner L, Hanl M, Hamacher A, Kassack MU, Hansen FK; Hydrazide-based class I HDAC inhibitors with HDAC3 preference completely reverse chemoresistance in a synergistic manner in platinum-resistant solid cancer cells. ChemRxiv 2024. doi: 10.26434/chemrxiv-2024-txxrk.
Huber ME, Wurnig SL, Moumbock AFA, Toy L, Kostenis E, Alonso Bartolomé A, Szpakowska M, Chevigné A, Günther S, Hansen FK, Schiedel M; Development of a NanoBRET Assay Platform to Detect Intracellular Ligands for the Chemokine Receptors CCR6 and CXCR1. ChemMedChem 2024:e202400284. doi: 10.1002/cmdc.202400284.
Behrmann LV, Meier K, Vollmer J, Chiedo CC, Schiefer A, Hörauf A, Pfarr K; In vitro extracellular replication of Wolbachia endobacteria. Front. Microbiol., 18 July 2024 Sec. Microbial Symbioses, Volume 15 - 2024 | https://doi.org/10.3389/fmicb.2024.1405287
Löckener I, Behrmann LV, Reuter J, Schiefer A, Klöckner A, Krannich S, Otten C, Mölleken K, Ichikawa S, Hoerauf A, Schneider T, Pfarr KM, Henrichfreise B; The MraY Inhibitor Muraymycin D2 and Its Derivatives Induce Enlarged Cells in Obligate Intracellular Chlamydia and Wolbachia and Break the Persistence Phenotype in Chlamydia.Antibiotics 2024, 13(5), 421; https://doi.org/10.3390/antibiotics13050421
Holze J, Lauber F, Kostenis E, Weindl G; Label-free biosensor assay decodes the dynamics of Toll-like receptor signaling. bioRxiv 2024.01.18.576268
Meringdal JW, Bade L, Bendas G, Menche D:Diversity Oriented Synthesis of Novel Xanthones Reveal Potent Doxorubicin-Inspired Analogs. ChemMedChem 2024:e202400055. doi: 10.1002/cmdc.202400055.
König B, Hansen FK; 2-(Difluoromethyl)-1,3,4-oxadiazoles: The Future of Selective Histone Deacetylase 6 Modulation? ACS Pharmacol. Transl. Sci. 2024. doi: 10.1021/acsptsci.4c00031.
Voget R, Breidenbach J, Claff T, Hingst A, Sylvester K, Steinebach C, Vu LP, Weiße R, Bartz U, Sträter N, Müller CE, Gütschow M; Development of an active-site titrant for SARS-CoV-2 main protease as an indispensable tool for evaluating enzyme kinetics. Acta Pharmaceutica Sinica B 2024; https://doi.org/10.1016/j.apsb.2024.03.001
Reverte-Salisa L, Sissig S, Hildebrand S, Yao X, Zurkovic J, Jaeckstein MY, Heeren J, Lezoualc'h F, Krahmer N, Pfeifer A; EPAC1 enhances brown fat growth and beige adipogenesis, Nat Cell Biol 26, 113–123 (2024). https://doi.org/10.1038/s41556-023-01311-9
Hopp MT, Holze J, Lauber F, Holtkamp L, Rathod DC, Miteva MA, Prestes EB, Geyer M, Manoury B, Merle NS, Roumenina LT, Bozza MT, Weindl G, Imhof D; Insights into the molecular basis and mechanism of heme-triggered TLR4 signalling: The role of heme-binding motifs in TLR4 and MD2. Immunology 171:181-197.
Pachòn-Angona I, Bernard PJ, Simakov A, Maj M, Jozwiak K, Novotna A, Lemke C, Gütschow M, Martin H, Oset-Gasque MJ, Marco-Contelles J, Ismaili L; Design and Synthesis of Multi-Functional Ligands through Hantzsch Reaction: Targeting Ca2+ Channels, Activating Nrf2 and Possessing Cathepsin S Inhibitory and Antioxidant Properties; Pharmaceutics 2024, 16, 121.
Kraft FB, Enns J, Honin I, Engelhardt J, Schöler A, Smith ST, Meiler J, Schäker-Hübner L, Weindl G, Hansen FK; Groebke Blackburn Bienaymé-mediated multi-component synthesis of selective HDAC6 inhibitors with anti-inflammatory properties. Bioorg Chem 2024; 143:107072. doi: 10.1016/j.bioorg.2023.107072.
Al Hamwi G, Namasivayam V, Büschbell B, Gedschold R, Golz S, Müller CE; Proinflammatory chemokine CXCL14 activates MAS-related G protein-coupled receptor MRGPRX2 and its putative mouse ortholog MRGPRB2. Commun. Biol. 2024, 7, 52; https://doi.org/10.1038/s42003-023-05739-5
Pepanian A, Sommerfeld P, Binbay FA, Fischer D, Pietsch M, Imhof D; In-depth analysis of Gαs protein activity by probing different fluorescently labeled guanine nucleotides. Biol. Chem., hsz-2023-0321
Tahoun M, Gee CT, Mc Coy, VE, Stoneman M, Raicu V, Engeser M, Müller CE; Suberin, the hallmark constituent of bark, identified in a 45-million-year-old monkeyhair tree (Coumoxylon hartigii) from Geiseltal, Germany. Scientific Reports 2024, 14, 118; https://doi.org/10.1038/s41598-023-50402-y.
Flury P, Breidenbach J, Krüger N, Voget R, Schäkel L, Si Y, Krasniqi V, Calistri S, Olfert M, Sylvester K, Rocha C, Ditzinger R, Rasch A, Pöhlmann S, Kronenberger T,
Poso A, Rox K, Laufer S, Müller CE, Gütschow M, Pillaiyar T; Cathepsin-targeting SARS-CoV-2 inhibitors: design, synthesis, and biological activity. ACS Pharmacol. Transl. Sci. 2024; https://doi.org/10.1021/acsptsci.3c00313
Pepanian A, Binbay FA, Pei D, Imhof D; Design, synthesis and analysis of macrobicyclic peptides for targeting the Gαi protein. J. Pept. Sci. 17:e3565
Yamauchi Y, Konno S, Omura N, Yoshioka N, Hingst A, Gütschow M, Müller CE, Taguchi A, Taniguchi A, Kawaguchi A, Hayashi Y; Detection of Active SARS-CoV-2 3CL Protease in Infected Cells Using Activity-Based Probes with a 2,6-Dichlorobenzoyloxymethyl Ketone Reactive Warhead. ACS Chem Biol. 2024 May 17;19(5):1028-1034. https:// doi:10.1021/acschembio.4c00024.
2023
Reverte-Salisa L, Siddig S, Hildebrand S, Zurkovic J, Jaeckstein MY, Heeren J, Lezoualch F, Krahmer N, Pfeifer A; EPAC1 enhances brown fat growth and beige adipogenesis; Nature Cell Biological 26, 113–123 (2024)
Steinebach C, Bricelj A, Murgai A, Sosič I, Bischof L, Ng YLD, Heim C, Maiwald S, Proj M, Voget R, Feller F, Košmrlj J, Sapozhnikova V, Schmidt A, Zuleeg MR, Lemnitzer P, Mertins P, Hansen FK, Gütschow M, Krönke J, Hartmann MD; Leveraging Ligand Affinity and Properties: Discovery of Novel Benzamide-Type Cereblon Binders for the Design of PROTACs; J. Med. Chem., 66, 14513-14543
Wollenhaupt C, Sudhop T, Knoess W. A Systematic Database Approach to Identify Companion Diagnostic Testing in Clinical Trials under the New In Vitro Diagnostic Medical Devices Regulation. Diagnostics. 2023; 13(12):2037. https://doi.org/10.3390/diagnostics13122037
Feller F, Hansen FK; Targeted Protein Degradation of Histone Deacetylases by Hydrophobically Tagged Inhibitors. ACS Med. Chem. Lett. 2023. doi: 10.1021/acsmedchemlett.3c00468
Günther M, Hentschel L, Schuler M, Müller T, Ko YD, Schmidet-Wolf I, Jaehde U; Developing tumor-specific PRO-CTCAE item sets: analysis of a cross-sectional survey in three German outpatient cancer centers, BMC Cancer 2023; 23:629, https://doi.org/10.1186/s12885-023-11115-7
Huber ME, Wurnig S, Toy L, Weiler C, Merten N, Kostenis E, Hansen FK, Schiedel M;
Fluorescent Ligands Enable Target Engagement Studies for the Intracellular Allosteric Binding Site of the Chemokine Receptor CXCR2. Journal of Medicinal Chemistry 2023. doi: 10.1021/acs.jmedchem.3c00769.
Hassan N, Bückreiß N, Efing J, Schulz-Fincke M, König P, Greve B, Bendas G, Götte M; The Heparan Sulfate Proteoglycan Syndecan-1 Triggers Breast Cancer Cell-Induced Coagulability by Induced Expression of Tissue Factor.Cells 2023; 12(6). doi: 10.3390/cells12060910.
Kraft FB, Hanl M, Feller F, Schäker-Hübner L, Hansen FK; Photocaged Histone Deacetylase Inhibitors as Prodrugs in Targeted Cancer Therapy. Pharmaceuticals 2023; 16(3):356. Verfügbar unter: https://www.mdpi.com/1424-8247/16/3/356.
Bachmann LM, Hanl M, Feller F, Sinatra L, Schöler A, Pietzsch J, Laube M, Hansen FK; Solid-Phase Parallel Synthesis of Dual Histone Deacetylase-Cyclooxygenase Inhibitors.
Molecules 2023; 28(3):1061. Verfügbar unter: https://www.mdpi.com/1420-3049/28/3/1061
Zhang HJ, Ociepa M, Nassir M, Zheng B, Lewicki S, Salmaso V, Baburi H, Nagel J, Mirza S, Büschbell B, Al-Hroub H, Perzanowska O, Lin Z, Schmidt MA, Eastgate MD, Jacobson KA, Müller CE, Kowalska J, Jemielity J, Baran PS; Stereocontrolled access to thioisosteres of nucleoside di- and triphosphates. Nature Chemistry 2023, https://doi.org/10.1038/s41557-023-01347-2.
Sinatra L, Vogelmann A, Friedrich F, Tararina MA, Neuwirt E, Colcerasa A, König P, Toy L, Yesiloglu TZ, Hilscher S, Gaitzsch L, Papenkordt N, Zhai S, Zhang L, Romier C, Einsle O, Sippl W, Schutkowski M, Gross O, Bendas G, Christianson DW, Hansen FK, Jung M, Schiedel M; Development of First-in-Class Dual Sirt2/HDAC6 Inhibitors as Molecular Tools for Dual Inhibition of Tubulin Deacetylation.Journal of Medicinal Chemistry 2023; 66(21):14787–814. doi: 10.1021/acs.jmedchem.3c01385.
Schmulenson E, Zimmermann N, Müller L, Kapsa S, Sihinevich I, Jaehde U; Influence of the skeletal muscle index on pharmacokinetics and toxicity of fluorouraci; Cancer Medicine 2023;12:2580-2589 lDOI: 10.1002/cam4.5118
Marx D, Mohamed Wessam Alnouri, Clemens S, Gedschold R, Riedel Y, Al Hamwi G, Pillaiyar T, Hockemeyer J, Namasivayam V, Müller CE; Discovery of potent agonists for the predominant variant of the orphan MAS-related G protein-coupled receptor X4 (MRGPRX4). J. Med. Chem. 2023, 66, 15674-15698; https://doi.org/10.3390/biom13071079.
Wurnig S, Vogt M, Hogenkamp J, Dienstbier N, Borkhardt A, Bhatia S, Hansen FK; Development of the first geldanamycin-based HSP90 degraders. Frontiers in Chemistry 2023; 11:1219883. doi: 10.3389/fchem.2023.1219883
Wollnitzke P, Wagner R, Afsar SY, Werner M, Gedschold R, Müller CE, Werz O, van Echten-Deckert G, Menche D; Synthesis and biological evaluation of simplified ajudazol derivatives reveal potent 5-lipoxygenase inhibition and considerable apoptotic activity in neuroblastoma cells.
Bioorg. Med. Chem. Lett. 2023, 94, 129464; https://doi.org/10.1016/j.bmcl.2023.129464.
König P, Zhulenko R, Suparman E, Hoffmeister H, Bückreiß N, Ott I, Bendas G; A biscarbene gold(I)-NHC-complex overcomes cisplatin-resistance in A2780 and W1 ovarian cancer cells highlighting pERK as regulator of apoptosis. Cancer Chemother Pharmacol 2023. doi: 10.1007/s00280-023-04548-1.
Giraulo C, Turiello R, Orlando L, Leonardelli S, Landsberg J, Belvedere R, Rolshoven G, Müller CE, Hölzel M, Morello S; The CD73 is induced by TGF-β1 triggered by nutrient deprivation and highly expressed in dedifferentiated human melanoma. Biomed. Pharmacother. 2023, 165, 115225; https://doi.org/j.biophar.2023.115225.
Bi C, Schäkel L, Mirza S, Sylvester K, Pelletier J, Lee SY, Pillaiyar, Sévigny J, Müller CE; Synthesis and structure-activity relationships of ticlopidine derivatives and analogs as inhibitors of ectonucleotidase CD39. Bioorg. Chem. 2023, 135, 106360; https://doi.org.10.1016/j.bioorg.2023.106460.
Voss JH, Crüsemann M, Bartling CRO, König GM, Strømgaard K, Müller, CE; Structure-affinity and structure-residence time relationships of macrocyclis Gαq protein inhibitors. iScience 2023, 26, 106492; https://doi.org/10.1016/j.isci.2023.106492.
Claff T, Schlegel JG, Voss JH, Vaaßen VJ, Weiße RH, Cheng RKY, Markovic-Mueller S, Bucher D, Sträter N, Müller CE; Crystal structure of adenosine A2A receptor in complex with clinical candidate Etrumadenant reveals unprecendented antagonist interaction. Commun. Chem. 2023, 6, 106; https://doi.org/10.1038/s42004-023-00894-6.
Pfeifer V, Weber H, Wang Y, Schlesinger M, Gorzelanny C, Bendas G; Exostosin 1 Knockdown Induces Chemoresistance in MV3 Melanoma Cells by Upregulating JNK and MEK/ERK Signaling. Int J Mol Sci 2023; 24(6). doi: 10.3390/ijms24065452.
Tsukamoto Y, Hiono T, Yamada S, Matsuno K, Faist A, Claff T, Hou J, Namasivayam V, vom Hemdt A, Sugimoto S, Ng JY, Christensen MH, Tesfamariam YM, Wolter S, Juranek,Zillinger T, Bauer S, Hirokawa T, Schmidt FI, Kochs G, Shimojima M, Huang YS, Pichlmair A, Kümmerer BM, Sakoda Y, Schlee M, Brunotte L, Müller CE, Igarashi M, Kato H; Inhibition of cellular RNA methyltransferase abrogates influenza virus capping and replication. Science 2023, 379, 586-591; https://doi.org/10.3390/ijms24043972
Geiger N, Diesendorf V, Roll V, Eva-Maria König, Obernolte H, Sewald K, Breidenbach J, Pillaiyar T, Gütschow M, Müller CE, Jochen Bodem; Cell type-specific anti-viral effects of novel SARS-CoV-2 main protease inhibitors. Int. J. Mol. Sci. 2023, 24, 3972; https://doi.org/10.3390/ijms24043972.
Voss JH, Al-Hroub H, Gedschold R, Dietrich JM, Gaffal E, Toma M, Kehraus S, König G M, Brust P, Fleischmann BK, Wenzel D, Deuther-Conrad W, Müller CE; Imaging of Gαq proteins in mouse and human organs and tissues.Pharmaceutics 2023, 15, 57; https://doi.org/10.3390/pharmaceutics15010057.
Lopez V, Schuh HJM, Mirza S, Vaassen VJ, Schmidt MS, Sylvester K, Idris RM, Renn C, Schäkel L, Pelletier J, Sévigny J, Naggi A, Scheffler B, Lee SY, Bendas G, Müller CE; Heparins are potent inhibitors of ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) – a promising target for the immunotherapy of cancer.
Front. Immunol. 2023, 14, 1173634; doi: 103389/fimmu2023.1173634.
Bockstiegel J, Engelhardt J, Weindl G; P2X7 receptor activation leads to NLRP3-independent IL-1β release by human macrophages. Cell Commun. Signal. 2023, 21, 335. doi: 10.1186/s12964-023-01356-1
Hopp MT, Holze J, Lauber F, Holtkamp L, Rathod DC, Miteva MA, Prestes EB, Geyer M, Manoury B, Merle NS, Roumenina LT, Bozza MT, Weindl G, Imhof D; Insights into the molecular basis and mechanism of heme-triggered TLR4 signalling: The role of heme-binding motifs in TLR4 and MD2. Immunology. 2023. doi: 10.1111/imm.13708
Dauer K, Kayser K, Ellwanger F, Overbeck A, Kwade A, Karbstein HP, Wagner KG;Highly protein-loaded melt extrudates produced by small-scale ram and twin-screw extrusion – evaluation of extrusion process design on protein stability by experimental and numerical approaches, International Journal of Pharmaceutics: X, July 2023. DOI: 10.1016/j.ijpx.2023.100196
König B, Watson PR, Reßling N, Cragin AD, Schäker-Hübner L, Christianson DW, Hansen FK; Difluoromethyl-1,3,4-oxadiazoles Are Selective, Mechanism-Based, and Essentially Irreversible Inhibitors of Histone Deacetylase 6. J.med. Chem.
Vu LP, Diehl CJ, Casement R, Bond AG, Steinebach C, Strašek N, Bricelj A, Perdih A, Schnakenburg G, Sosič I, Ciulli A, Gütschow M; Expanding the Structural Diversity at the Phenylene Core of Ligands for the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase: Development of Highly Potent Hypoxia-Inducible Factor-1α (HIF-1α) Stabilizers. J. Med. Chem. 2023, 66, 12776-12811
Keuler T, Wolf V, Lemke C, Voget R, Braune A, Gütschow M; Fluorogenic Substrates and Pre‐column Derivatization for Monitoring the Activity of Bile Salt Hydrolase from Clostridium perfringens. Bioorg. Chem. 2023, 138, 106574
Pepanian A, Binby FA, Roy S, Nubbemeyer B, Koley A, Rhodes CA; Ammer H, Pei D, Ghosh P, Imhof D; Bicyclic peptide library screening for the identification of Gαi protein modulators. J.Med. Chem.
Bockstiegel J, Wurmig SL, Engelhardt J, Enns J, Hansen FK, Weindl G; Pharmacological inhibition of HDAC6 suppresses NLRP3 inflammasome-mediated IL-1β release. Biochem Pharmacol 215: 115693.
Tahoun M, Engener M, Svolacchia L, Sander M, Müller CE; Molecular Taphonomy of Heme: Chemical Degradation of Hemin under Presumed Fossilization Conditions. Molecules 2023
Javed H, Singh S, Urs Ramarajje S, Oldenburg J, Biswas A; Genetic landscape in coagulation factor XIII associated defects - Advances in coagulation and beypong. Blood Reviews
Ng YLD, Bricelj A, Jansen JA, Murgai A, Peter K, Donovan KA, Gütschow M, Krönke J, Steinebach C, Sosič I: Heterobifunctional Ligase Recruiters Enable Pan-Degradation of Inhibitor of Apoptosis Proteins. J. Med. Chem. 2023, 66, 4703-4733
Kuchta R, Heim C, Herrmann A, Maiwald S, Ng YLD, Sosič I, Keuler T, Krönke J, Gütschow M, Hartmann MD, Steinebach C; Accessing Three-Branched High-Affinity Cereblon Ligands for Molecular Glue and Protein Degrader Design. RSC Chem. Biol. 2023, 4, 229-234
Pöstges F, Kayser K, Appelhaus J, Monschke M, Gütschow M, Steinebach C, Wagner KG; Solubility Enhanced Formulation Approaches to Overcome Oral Delivery Obstacles of PROTACs. Pharmaceutics 2023, 15, 156
Dauer K, Wagner KG; Micro-Scale Vacuum Compression Molding as a Predictive Sdreening Tool of Protein Integrity for Potential Hot-Melt extrusion Processes. Pharmaceutics