Publications | Structural Genomics Consortium

Discovery of a Novel DCAF1 Ligand Using a Drug-Target Interaction Prediction Model: Generalizing Machine Learning to New Drug Targets.

Kimani SW, Owen J, Green SR, Li F, Li Y, Dong A, Brown PJ, Ackloo S, Kuter D, Yang C, MacAskill M, MacKinnon SS, Arrowsmith CH, Schapira M, Shahani V, Halabelian L

J Chem Inf Model. doi: 10.1021/acs.jcim.3c00082

Publication date: June 23, 2023

PMID: 37350740

Target 2035 - an update on private sector contributions.

Ackloo S, Antolin AA, Bartolome JM, Beck H, Bullock A, Betz UAK, BÃ¶ttcher J, Brown PJ, Chaturvedi M, Crisp A, Daniels D, Dreher J, Edfeldt K, Edwards AM, Egner U, Elkins J, Fischer C, Glendorf T, Goldberg S, Hartung IV, Hillisch A, Homan E, Knapp S, KÃ¶ster M, KrÃ¤mer O, Llaveria J, Lessel U, Lindemann S, Linderoth L, Matsui H, Michel M, Montel F, Mueller-Fahrnow A, Müller S, Owen DR, Saikatendu KS, Santhakumar V, Sanderson W, Scholten C, Schapira M, Sharma S, Shireman B, SundstrÃ¶m M, Todd MH, Tredup C, Venable J, Willson TM, Arrowsmith CH

RSC Med Chem. 14(6):1002-1011. doi: 10.1039/d2md00441k

Publication date: June 22, 2023

PMID: 37360399

Delineation of functional subdomains of Huntingtin protein and their interaction with HAP40.

Alteen MG, Deme JC, Alvarez CP, Loppnau P, Hutchinson A, Seitova A, Chandrasekaran R, Silva Ramos E, Secker C, Alqazzaz M, Wanker EE, Lea SM, Arrowsmith CH, Harding RJ

Structure. doi: 10.1016/j.str.2023.06.002

Publication date: June 20, 2023

PMID: 37390814

Tracking the PROTAC degradation pathway in living cells highlights the importance of ternary complex measurement for PROTAC optimization.

Schwalm MP, KrÃ¤mer A, DÃ¶lle A, Weckesser J, Yu X, Jin J, Saxena K, Knapp S

Cell Chem Biol. doi: 10.1016/j.chembiol.2023.06.002

Publication date: June 20, 2023

PMID: 37354907

Structure-Based Discovery of Inhibitors of the SARS-CoV-2 Nsp14 N7-Methyltransferase.

Singh I, Li F, Fink EA, Chau I, Li A, Rodriguez-HernÃ¡ndez A, Glenn I, Zapatero-BelinchÃ³n FJ, Rodriguez ML, Devkota K, Deng Z, White K, Wan X, Tolmachova NA, Moroz YS, Kaniskan HÃœ, Ott M, GarcÃa-Sastre A, Jin J, Fujimori DG, Irwin JJ, Vedadi M, Shoichet BK

J Med Chem. doi: 10.1021/acs.jmedchem.2c02120

Publication date: June 9, 2023

PMID: 37294077

Design and Synthesis of Pyrazole-Based Macrocyclic Kinase Inhibitors Targeting BMPR2.

Amrhein JA, Wang G, Berger BT, Berger LM, Kalampaliki AD, KrÃ¤mer A, Knapp S, Hanke T

ACS Med Chem Lett. 14(6):833-840. doi: 10.1021/acsmedchemlett.3c00127

Publication date: June 8, 2023

PMID: 37312836

Structural insights into a regulatory mechanism of FIR RRM1-FUSE interaction.

Ni X, Joerger AC, Chaikuad A, Knapp S

Open Biol. 13(5):230031. doi: 10.1098/rsob.230031

Publication date: May 31, 2023

PMID: 37253421

Mutation in the Common Docking Domain Affects MAP Kinase ERK2 Catalysis and Stability.

Novak L, Petrosino M, Pasquo A, Chaikuad A, Chiaraluce R, Knapp S, Consalvi V

Cancers (Basel). 15(11):. doi: 10.3390/cancers15112938

Publication date: May 26, 2023

PMID: 37296900

Identification of inhibitors for the trans-membrane Trypanosoma cruzi eIF2Î± kinase relevant for parasite proliferation.

Marcelino TP, Fala AM, da Silva MM, Souza-Melo N, Malvezzi AM, Klippel AH, Zoltner M, Padilla-Mejia N, Kosto S, Field MC, Burle Caldas GA, Teixeira SMR, CouÃ±ago RM, Massirer KB, Schenkman S

J Biol Chem. 104857. doi: 10.1016/j.jbc.2023.104857

Publication date: May 23, 2023

PMID: 37230387

Open drug discovery in Alzheimer's disease.

Axtman AD, Brennan PE, Frappier-Brinton T, Betarbet R, Carter GW, Fu H, Gileadi O, Greenwood AK, Leal K, Longo FM, Mangravite LM, Edwards AM, Levey AI

Alzheimers Dement (N Y). 9(2):e12394. doi: 10.1002/trc2.12394

Publication date: May 22, 2023

PMID: 37215505

Structure-Based Development of Isoform-Selective Inhibitors of Casein Kinase 1Îµ vs Casein Kinase 1Î´.

Choi JY, Noguchi Y, Alburger JM, Bayle S, Chung E, Grant W, Chaikuad A, Knapp S, Duckett DR, Roush WR

J Med Chem. doi: 10.1021/acs.jmedchem.2c01180

Publication date: May 19, 2023

PMID: 37204207

Targeting the Divergent Roles of STK3 Inhibits Breast Cancer Cell Growth and Opposes Doxorubicin-Induced Cardiotoxicity In Vitro.

Nam J, Schirmer AU, Loh C, Drewry DH, Macias E

Cancers (Basel). 15(10):. doi: 10.3390/cancers15102817

Publication date: May 18, 2023

PMID: 37345153

A Small Step Toward Generalizability: Training a Machine Learning Scoring Function for Structure-Based Virtual Screening.

Scantlebury J, Vost L, Carbery A, Hadfield TE, Turnbull OM, Brown N, Chenthamarakshan V, Das P, Grosjean H, von Delft F, Deane CM

J Chem Inf Model. doi: 10.1021/acs.jcim.3c00322

Publication date: May 11, 2023

PMID: 37166179

A novel BRET-based assay to investigate binding and residence times of unmodified ligands to the human lysosomal ion channel TRPML1 in intact cells.

Cunha MR, Catta-Preta CMC, Takarada JE, Moreira GA, Massirer KB, CouÃ±ago RM

J Biol Chem. 104807. doi: 10.1016/j.jbc.2023.104807

Publication date: May 10, 2023

PMID: 37172730

Editorial: The next generation of tools and technologies for studying human neurons in a dish.

Durcan TM, Axtman AD

Front Cell Neurosci. 17:1196543. doi: 10.3389/fncel.2023.1196543

Publication date: May 1, 2023

PMID: 37124399

NMR resonance assignment of a fibroblast growth factor 8 splicing isoform b.

Hargittay B, Mineev KS, Richter C, Sreeramulu S, Jonker HRA, Saxena K, Schwalbe H

Biomol NMR Assign. doi: 10.1007/s12104-023-10132-8

Publication date: April 29, 2023

PMID: 37118562

Discovery of a Potent and Selective CDKL5/GSK3 Chemical Probe That Is Neuroprotective.

Ong HW, Liang Y, Richardson W, Lowry ER, Wells CI, Chen X, Silvestre M, Dempster K, Silvaroli JA, Smith JL, Wichterle H, Pabla NS, Ultanir SK, Bullock AN, Drewry DH, Axtman AD

ACS Chem Neurosci. doi: 10.1021/acschemneuro.3c00135

Publication date: April 21, 2023

PMID: 37084253

Structural insights into DNA recognition by the BEN domain of the transcription factor BANP.

Liu K, Zhang J, Xiao Y, Yang A, Song X, Li Y, Chen Y, Hughes TR, Min J

J Biol Chem. 104734. doi: 10.1016/j.jbc.2023.104734

Publication date: April 20, 2023

PMID: 37086783

Modulation of tau tubulin kinases (TTBK1 and TTBK2) impacts ciliogenesis.

Bashore FM, Marquez AB, Chaikuad A, Howell S, Dunn AS, Beltran AA, Smith JL, Drewry DH, Beltran AS, Axtman AD

Sci Rep. 13(1):6118. doi: 10.1038/s41598-023-32854-4

Publication date: April 14, 2023

PMID: 37059819

Discovery of a Potent and Selective Naphthyridine-Based Chemical Probe for Casein Kinase 2.

Davis-Gilbert ZW, KrÃ¤mer A, Dunford JE, Howell S, Senbabaoglu F, Wells CI, Bashore FM, Havener TM, Smith JL, Hossain MA, Oppermann U, Drewry DH, Axtman AD

ACS Med Chem Lett. 14(4):432-441. doi: 10.1021/acsmedchemlett.2c00530

Publication date: April 13, 2023

PMID: 37077385

A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi.

Dos Reis TF, de Castro PA, Bastos RW, Pinzan CF, Souza PFN, Ackloo S, Hossain MA, Drewry DH, Alkhazraji S, Ibrahim AS, Jo H, Lightfoot JD, Adams EM, Fuller KK, deGrado WF, Goldman GH

Nat Commun. 14(1):2052. doi: 10.1038/s41467-023-37573-y

Publication date: April 12, 2023

PMID: 37045836

Shifting the selectivity of pyrido[2,3-d]pyrimidin-7(8H)-one inhibitors towards the salt-inducible kinase (SIK) subfamily.

Rak M, Tesch R, Berger LM, Shevchenko E, Raab M, Tjaden A, Zhubi R, Balourdas DI, Joerger AC, Poso A, KrÃ¤mer A, Elson L, LuÄiÄ‡ A, Kronenberger T, Hanke T, Strebhardt K, Sanhaji M, Knapp S

Eur J Med Chem. 254:115347. doi: 10.1016/j.ejmech.2023.115347

Publication date: April 7, 2023

PMID: 37094449

Discovery of a Potent and Selective Targeted NSD2 Degrader for the Reduction of H3K36me2.

Hanley RP, Nie DY, Tabor JR, Li F, Sobh A, Xu C, Barker NK, Dilworth D, Hajian T, Gibson E, Szewczyk MM, Brown PJ, Barsyte-Lovejoy D, Herring LE, Wang GG, Licht JD, Vedadi M, Arrowsmith CH, James LI

J Am Chem Soc. doi: 10.1021/jacs.3c01421

Publication date: March 28, 2023

PMID: 36976643

Development of Cell Permeable NanoBRET Probes for the Measurement of PLK1 Target Engagement in Live Cells.

Yang X, Smith JL, Beck MT, Wilkinson JM, Michaud A, Vasta JD, Robers MB, Willson TM

Molecules. 28(7):. doi: 10.3390/molecules28072950

Publication date: March 25, 2023

PMID: 37049713

Discovery of Nanomolar DCAF1 Small Molecule Ligands.

Li ASM, Kimani S, Wilson B, Noureldin M, González-Álvarez H, Mamai A, Hoffer L, Guilinger JP, Zhang Y, von Rechenberg M, Disch JS, Mulhern CJ, Slakman BL, Cuozzo JW, Dong A, Poda G, Mohammed M, Saraon P, Mittal M, Modh P, Rathod V, Patel B, Ackloo S, Santhakumar V, Szewczyk MM, Barsyte-Lovejoy D, Arrowsmith CH, Marcellus R, Guié MA, Keefe AD, Brown PJ, Halabelian L, Al-Awar R, Vedadi M

J Med Chem. doi: 10.1021/acs.jmedchem.2c02132

Publication date: March 22, 2023

PMID: 36948210

Deep Annotation of Donated Chemical Probes (DCP) in Organotypic Human Liver Cultures and Patient-Derived Organoids from Tumor and Normal Colorectum.

Tredup C, Ndreshkjana B, Schneider NS, Tjaden A, Kemas AM, Youhanna S, Lauschke VM, Berger BT, Krämer A, Berger LM, Röhm S, Knapp S, Farin HF, Müller S

ACS Chem Biol. doi: 10.1021/acschembio.2c00877

Publication date: March 21, 2023

PMID: 36944371

Reference compounds for characterizing cellular injury in high-content cellular morphology assays.

Dahlin JL, Hua BK, Zucconi BE, Nelson SD, Singh S, Carpenter AE, Shrimp JH, Lima-Fernandes E, Wawer MJ, Chung LPW, Agrawal A, O'Reilly M, Barsyte-Lovejoy D, Szewczyk M, Li F, Lak P, Cuellar M, Cole PA, Meier JL, Thomas T, Baell JB, Brown PJ, Walters MA, Clemons PA, Schreiber SL, Wagner BK

Nat Commun. 14(1):1364. doi: 10.1038/s41467-023-36829-x

Publication date: March 13, 2023

PMID: 36914634

Chemistry-led investigations into the mode of action of NAMPT activators, resulting in the discovery of non-pyridyl class NAMPT activators.

Tang S, Garzon Sanz M, Smith O, Krämer A, Egbase D, Caton PW, Knapp S, Butterworth S

Acta Pharm Sin B. 13(2):709-721. doi: 10.1016/j.apsb.2022.07.016

Publication date: March 7, 2023

PMID: 36873168

Oxazolo[5,4-f]quinoxaline-type selective inhibitors of glycogen synthase kinase-3α (GSK-3α): Development and impact on temozolomide treatment of glioblastoma cells.

Hasyeoui M, Lassagne F, Erb W, Nael M, Elokely KM, Chaikuad A, Knapp S, Jorda A, Vallés SL, Quissac E, Verreault M, Robert T, Bach S, Samarat A, Mongin F

Bioorg Chem. 134:106456. doi: 10.1016/j.bioorg.2023.106456

Publication date: March 4, 2023

PMID: 36913879

RAS and PP2A activities converge on epigenetic gene regulation.

Aakula A, Sharma M, Tabaro F, Nätkin R, Kamila J, Honkanen H, Schapira M, Arrowsmith C, Nykter M, Westermarck J

Life Sci Alliance. 6(5):. doi: 10.26508/lsa.202301928

Publication date: March 2, 2023

PMID: 36858798

Design, synthesis and characterisation of a novel type II B-RAF paradox breaker inhibitor.

Arora R, Linders JTM, Aci-Sèche S, Verheyen T, Van Heerde E, Brehmer D, Chaikuad A, Knapp S, Bonnet P

Eur J Med Chem. 250:115231. doi: 10.1016/j.ejmech.2023.115231

Publication date: February 25, 2023

PMID: 36878151

Histone H4K20 monomethylation enables recombinant nucleosome methylation by PRMT1 in vitro.

Li ASM, Homsi C, Bonneil E, Thibault P, Verreault A, Vedadi M

Biochim Biophys Acta Gene Regul Mech. 194922. doi: 10.1016/j.bbagrm.2023.194922

Publication date: February 21, 2023

PMID: 36822575

Discovery and Characterization of BAY-805, a Potent and Selective Inhibitor of Ubiquitin-Specific Protease USP21.

Göricke F, Vu V, Smith L, Scheib U, Böhm R, Akkilic N, Wohlfahrt G, Weiske J, Bömer U, Brzezinka K, Lindner N, Lienau P, Gradl S, Beck H, Brown PJ, Santhakumar V, Vedadi M, Barsyte-Lovejoy D, Arrowsmith CH, Schmees N, Petersen K

J Med Chem. doi: 10.1021/acs.jmedchem.2c01933

Publication date: February 20, 2023

PMID: 36802665

Discovery and Development Strategies for SARS-CoV-2 NSP3 Macrodomain Inhibitors.

Schuller M, Zarganes-Tzitzikas T, Bennett J, De Cesco S, Fearon D, von Delft F, Fedorov O, Brennan PE, Ahel I

Pathogens. 12(2):. doi: 10.3390/pathogens12020324

Publication date: February 15, 2023

PMID: 36839595

Toward effective Atg8-based ATTECs: Approaches and perspectives.

Schwalm MP, Knapp S, Rogov VV

J Cell Biochem. doi: 10.1002/jcb.30380

Publication date: February 13, 2023

PMID: 36780422

SS148 and WZ16 inhibit the activities of nsp10-nsp16 complexes from all seven human pathogenic coronaviruses.

Li F, Ghiabi P, Hajian T, Klima M, Li ASM, Yazdi AK, Chau I, Loppnau P, Kutera M, Seitova A, Bolotokova A, Hutchinson A, Perveen S, Boura E, Vedadi M

Biochim Biophys Acta Gen Subj. 130319. doi: 10.1016/j.bbagen.2023.130319

Publication date: February 8, 2023

PMID: 36764586

Antecedent chromatin organization determines cGAS recruitment to ruptured micronuclei.

MacDonald KM, Nicholson-Puthenveedu S, Tageldein MM, Khasnis S, Arrowsmith CH, Harding SM

Nat Commun. 14(1):556. doi: 10.1038/s41467-023-36195-8

Publication date: February 2, 2023

PMID: 36732527

Epigenetic modulation by targeting bromodomain containing protein 9 (BRD9): Its therapeutic potential and selective inhibition.

Ali MM, Naz S, Ashraf S, Knapp S, Ul-Haq Z

Int J Biol Macromol. 123428. doi: 10.1016/j.ijbiomac.2023.123428

Publication date: January 26, 2023

PMID: 36709803

Studying Protein Arginine Methylation: Approaches and Methods.

Barsyte-Lovejoy D

J Vis Exp. doi: 10.3791/64821

Publication date: January 20, 2023

PMID: 37602846

Detection of antibodies against the huntingtin protein in human plasma.

Denis HL, Alpaugh M, Alvarez CP, Fenyi A, Barker RA, Chouinard S, Arrowsmith CH, Melki R, Labib R, Harding RJ, Cicchetti F

Cell Mol Life Sci. 80(2):45. doi: 10.1007/s00018-023-04687-x

Publication date: January 18, 2023

PMID: 36651994

Death by a Thousand Cuts â€" Combining Kinase Inhibitors for Selective Target Inhibition and Rational Polypharmacology.

Outhwaite IR, Singh S, Berger BT, Knapp S, Chodera JD, Seeliger MA

bioRxiv. doi: 10.1101/2023.01.13.523972

Publication date: January 16, 2023

PMID: 36711619

SGC-CAMKK2-1: A Chemical Probe for CAMKK2.

Wells C, Liang Y, Pulliam TL, Lin C, Awad D, Eduful B, O'Byrne S, Hossain MA, Catta-Preta CMC, Ramos PZ, Gileadi O, Gileadi C, Couñago RM, Stork B, Langendorf CG, Nay K, Oakhill JS, Mukherjee D, Racioppi L, Means AR, York B, McDonnell DP, Scott JW, Frigo DE, Drewry DH

Cells. 12(2):. doi: 10.3390/cells12020287

Publication date: January 11, 2023

PMID: 36672221

Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 macrodomain of SARS-CoV-2.

Gahbauer S, Correy GJ, Schuller M, Ferla MP, Doruk YU, Rachman M, Wu T, Diolaiti M, Wang S, Neitz RJ, Fearon D, Radchenko DS, Moroz YS, Irwin JJ, Renslo AR, Taylor JC, Gestwicki JE, von Delft F, Ashworth A, Ahel I, Shoichet BK, Fraser JS

Proc Natl Acad Sci U S A. 120(2):e2212931120. doi: 10.1073/pnas.2212931120

Publication date: January 10, 2023

PMID: 36598939

Discovery of potent Plasmodium falciparum protein kinase 6 (PfPK6) inhibitors with a type II inhibitor pharmacophore.

Ong HW, Truong A, Kwarcinski F, de Silva C, Avalani K, Havener TM, Chirgwin M, Galal KA, Willis C, Krämer A, Liu S, Knapp S, Derbyshire ER, Zutshi R, Drewry DH

Eur J Med Chem. 249:115043. doi: 10.1016/j.ejmech.2022.115043

Publication date: December 30, 2022

PMID: 36736152

Development of a Potent Cyclic Peptide Inhibitor of the nNOS/PSD-95 Interaction.

Balboa JR, Essig DJ, Ma S, Karer N, Clemmensen LS, Pedersen SW, Joerger AC, Knapp S, Østergaard S, Strømgaard K

J Med Chem. doi: 10.1021/acs.jmedchem.2c01803

Publication date: December 29, 2022

PMID: 36580549

Systematic Design of Adenosine Analogs as Inhibitors of a Clostridioides difficile-Specific DNA Adenine Methyltransferase Required for Normal Sporulation and Persistence.

Zhou J, Horton JR, Menna M, Fiorentino F, Ren R, Yu D, Hajian T, Vedadi M, Mazzoccanti G, Ciogli A, Weinhold E, Hüben M, Blumenthal RM, Zhang X, Mai A, Rotili D, Cheng X

J Med Chem. doi: 10.1021/acs.jmedchem.2c01789

Publication date: December 29, 2022

PMID: 36581322