Publications | Structural Genomics Consortium

A Target Class Ligandability Evaluation of WD40 Repeat-Containing Proteins.

Ackloo S, Li F, Szewczyk M, Seitova A, Loppnau P, Zeng H, Xu J, Ahmad S, Arnautova YA, Baghaie AJ, Beldar S, Bolotokova A, Centrella PA, Chau I, Clark MA, Cuozzo JW, Dehghani-Tafti S, Disch JS, Dong A, Dumas A, Feng JA, Ghiabi P, Gibson E, Gilmer J, Goldman B, Green SR, Guié MA, Guilinger JP, Harms N, Herasymenko O, Houliston S, Hutchinson A, Kearnes S, Keefe AD, Kimani SW, Kramer T, Kutera M, Kwak HA, Lento C, Li Y, Liu J, Loup J, Machado RAC, Mulhern CJ, Perveen S, Righetto GL, Riley P, Shrestha S, Sigel EA, Silva M, Sintchak MD, Slakman BL, Taylor RD, Thompson J, Torng W, Underkoffler C, von Rechenberg M, Walsh RT, Watson I, Wilson DJ, Wolf E, Yadav M, Yazdi AK, Zhang J, Zhang Y, Santhakumar V, Edwards AM, Barsyte-Lovejoy D, Schapira M, Brown PJ, Halabelian L, Arrowsmith CH

J Med Chem. doi: 10.1021/acs.jmedchem.4c02010

Publication date: November 4, 2024

PMID: 39495097

Inhibiting EZH2 targets atypical teratoid rhabdoid tumor by triggering viral mimicry via both RNA and DNA sensing pathways.

Feng S, Marhon SA, Sokolowski DJ, D'Costa A, Soares F, Mehdipour P, Ishak C, Loo Yau H, Ettayebi I, Patel PS, Chen R, Liu J, Zuzarte PC, Ho KC, Ho B, Ning S, Huang A, Arrowsmith CH, Wilson MD, Simpson JT, De Carvalho DD

Nat Commun. 15(1):9321. doi: 10.1038/s41467-024-53515-8

Publication date: October 30, 2024

PMID: 39472584

Rational fragment-based design of compounds targeting the PWWP domain of the HRP family.

Vantieghem T, Aslam NA, Osipov EM, Akele M, Van Belle S, Beelen S, Drexler M, Paulovcakova T, Lux V, Fearon D, Douangamath A, von Delft F, Christ F, Veverka V, Verwilst P, Van Aerschot A, Debyser Z, Strelkov SV

Eur J Med Chem. 280:116960. doi: 10.1016/j.ejmech.2024.116960

Publication date: October 27, 2024

PMID: 39461037

Convergence on CaMK4: a key modulator of autism-associated signaling pathways in neurons.

Kaiser J, Risteska A, Muller AG, Sun H, Lei B, Nay K, Means AR, Cousin MA, Drewry DH, Oakhill JS, Kemp BE, Hannan AJ, Berk M, Febbraio MA, Gundlach AL, Hill-Yardin EL, Scott JW

Biol Psychiatry. doi: 10.1016/j.biopsych.2024.10.012

Publication date: October 24, 2024

PMID: 39442785

TP53: the unluckiest of genes?

Joerger AC, Stiewe T, Soussi T

Cell Death Differ. doi: 10.1038/s41418-024-01391-6

Publication date: October 24, 2024

PMID: 39443700

Oxadiazolone-Based Aromatic Annulations: A Nitrenoid Precursor for Tricyclic Aminoheterocycles.

Zhu WF, Franz HM, Krämer A, Duman E, Empel C, Göbel MW, Koenigs RM, Knapp S, Hiesinger K, Proschak E, Hernandez-Olmos V

J Org Chem. doi: 10.1021/acs.joc.4c01622

Publication date: October 23, 2024

PMID: 39438325

A guide to selecting high-performing antibodies for PLC-gamma-2 for use in Western Blot, immunoprecipitation and immunofluorescence.

Ruíz Moleón V, Fotouhi M, Alende C, Ayoubi R, Bedford LM, Southern K, Richardson TI, Laflamme C

F1000Res. 13:77. doi: 10.12688/f1000research.146156.1

Publication date: October 21, 2024

PMID: 39429638

A guide to selecting high-performing antibodies for CSNK2A1 (UniProt ID: P68400) for use in western blot, immunoprecipitation and immunofluorescence.

Ayoubi R, Fotouhi M, Alende C, Ruíz Moleón V, Southern K, Laflamme C

F1000Res. 13:781. doi: 10.12688/f1000research.153243.2

Publication date: October 15, 2024

PMID: 39403680

The use of a multi-metric readout screen to identify EHMT2/G9a-inhibition as a modulator of cancer-associated fibroblast activation state.

Wu NC, Quevedo R, Nurse M, Hezaveh K, Liu H, Sun F, Muffat J, Sun Y, Simmons CA, McGaha TL, Prinos P, Arrowsmith CH, Ailles L, D'Arcangelo E, McGuigan AP

Biomaterials. 314:122879. doi: 10.1016/j.biomaterials.2024.122879

Publication date: October 13, 2024

PMID: 39395244

Identification of a cell-active chikungunya virus nsP2 protease inhibitor using a covalent fragment-based screening approach.

Merten EM, Sears JD, Leisner TM, Hardy PB, Ghoshal A, Hossain MA, Asressu KH, Brown PJ, Tse EG, Stashko MA, Li K, Norris-Drouin JL, Herring LE, Mordant AL, Webb TS, Mills CA, Barker NK, Streblow ZJ, Perveen S, Arrowsmith CH, Couñago RM, Arnold JJ, Cameron CE, Streblow DN, Moorman NJ, Heise MT, Willson TM, Popov KI, Pearce KH

Proc Natl Acad Sci U S A. 121(42):e2409166121. doi: 10.1073/pnas.2409166121

Publication date: October 10, 2024

PMID: 39388272

An Adenosine Analogue Library Reveals Insights into Active Sites of Protein Arginine Methyltransferases and Enables the Discovery of a Selective PRMT4 Inhibitor.

Deng Y, Kim EJ, Song X, Kulkarni AS, Zhu RX, Wang Y, Bush M, Dong A, Noinaj N, Min J, Xu W, Huang R

J Med Chem. doi: 10.1021/acs.jmedchem.4c01041

Publication date: October 4, 2024

PMID: 39361813

A guide to selecting high-performing antibodies for amyloid-beta precursor protein for use in Western Blot, immunoprecipitation and immunofluorescence.

Ayoubi R, Fotouhi M, Worrall D, Southern K, Laflamme C

F1000Res. 12:956. doi: 10.12688/f1000research.139867.2

Publication date: October 3, 2024

PMID: 39359612

Unlocking the potential: unveiling tyrphostins with Michael-reactive cyanoacrylate motif as promising inhibitors of human 5-lipoxygenase.

Molitor M, Menge A, Mandel S, George S, Müller S, Knapp S, Hofmann B, Steinhilber D, Häfner AK

Pflugers Arch. doi: 10.1007/s00424-024-03019-7

Publication date: September 30, 2024

PMID: 39347835

Poly ADP-ribose signaling is dysregulated in Huntington disease.

Maiuri T, Bazan CB, Harding RJ, Begeja N, Kam TI, Byrne LM, Rodrigues FB, Warner MM, Neuman K, Mansoor M, Badiee M, Dasovich M, Wang K, Thompson LM, Leung AKL, Andres SN, Wild EJ, Dawson TM, Dawson VL, Arrowsmith CH, Truant R

Proc Natl Acad Sci U S A. 121(40):e2318098121. doi: 10.1073/pnas.2318098121

Publication date: September 27, 2024

PMID: 39331414

A guide to selecting high-performing antibodies for Secreted frizzled-related protein 1 (sFRP-1) for use in Western Blot and immunoprecipitation.

Ayoubi R, Southern K, Laflamme C

F1000Res. 12:291. doi: 10.12688/f1000research.130991.2

Publication date: September 25, 2024

PMID: 39319244

Activation of parkin by a molecular glue.

Sauvé V, Stefan E, Croteau N, Goiran T, Fakih R, Bansal N, Hadzipasic A, Fang J, Murugan P, Chen S, Fon EA, Hirst WD, Silvian LF, Trempe JF, Gehring K

Nat Commun. 15(1):7707. doi: 10.1038/s41467-024-51889-3

Publication date: September 20, 2024

PMID: 39300082

PRMT1 inhibition perturbs RNA metabolism and induces DNA damage in clear cell renal cell carcinoma.

Walton J, Ng ASN, Arevalo K, Apostoli A, Meens J, Karamboulas C, St-Germain J, Prinos P, Dmytryshyn J, Chen E, Arrowsmith CH, Raught B, Ailles L

Nat Commun. 15(1):8232. doi: 10.1038/s41467-024-52507-y

Publication date: September 20, 2024

PMID: 39300069

Identification of high-performing antibodies for SPARC-related modular calcium-binding protein 1 (SMOC-1) for use in Western Blot and immunoprecipitation.

Ayoubi R, González Bolívar S, Nicouleau M, Southern K, Laflamme C

F1000Res. 12:1279. doi: 10.12688/f1000research.141800.2

Publication date: September 18, 2024

PMID: 39291144

Strategic Fluorination to Achieve a Potent, Selective, Metabolically Stable, and Orally Bioavailable Inhibitor of CSNK2.

Ong HW, Yang X, Smith JL, Taft-Benz S, Howell S, Dickmander RJ, Havener TM, Sanders MK, Brown JW, Couñago RM, Chang E, Krämer A, Moorman NJ, Heise M, Axtman AD, Drewry DH, Willson TM

Molecules. 29(17):. doi: 10.3390/molecules29174158

Publication date: September 14, 2024

PMID: 39275006

A guide to selecting high-performing antibodies for Huntingtin (UniProt ID: P42858) for use in western blot, immunoprecipitation, and immunofluorescence.

Fanti R, Ayoubi R, Alende C, Fotouhi M, González Bolívar S, Chandrasekaran R, Southern K, Edwards AM, Harding RJ, Laflamme C

F1000Res. 13:922. doi: 10.12688/f1000research.153670.1

Publication date: September 11, 2024

PMID: 39257448

Elimination of mutant SWI/SNF complexes by protein quality control: new opportunities targeting aggressive rhabdoid tumours.

Krämer A, Knapp S

Signal Transduct Target Ther. 9(1):224. doi: 10.1038/s41392-024-01935-9

Publication date: September 6, 2024

PMID: 39237495

Structure Activity of β-Amidomethyl Vinyl Sulfones as Covalent Inhibitors of Chikungunya nsP2 Cysteine Protease with Antialphavirus Activity.

Ghoshal A, Asressu KH, Hossain MA, Brown PJ, Nandakumar M, Vala A, Merten EM, Sears JD, Law I, Burdick JE, Morales NL, Perveen S, Pearce KH, Popov KI, Moorman NJ, Heise MT, Willson TM

J Med Chem. doi: 10.1021/acs.jmedchem.4c01346

Publication date: September 5, 2024

PMID: 39235978

A guide to selecting high-performing antibodies for Protein-glutamine gamma-glutamyltransferase 2 (TGM2) for use in western blot, immunoprecipitation and immunofluorescence.

Ayoubi R, Fotouhi M, Alende C, González Bolívar S, Southern K, Laflamme C

F1000Res. 13:481. doi: 10.12688/f1000research.150684.2

Publication date: September 2, 2024

PMID: 39220380

Autoinhibition of ubiquitin-specific protease 8: insights into domain interactions and mechanisms of regulation.

Caba C, Black M, Liu Y, DaDalt AA, Mallare J, Fan L, Harding RJ, Wang Y, Vacratsis PO, Huang R, Zhuang Z, Tong Y

J Biol Chem. 107727. doi: 10.1016/j.jbc.2024.107727

Publication date: August 28, 2024

PMID: 39214302

Inhibition of bromodomain and extra-terminal proteins targets constitutively active NFκB and STAT signaling in lymphoma and influences the expression of the antiapoptotic proteins BCL2A1 and c-MYC.

Pieper NM, Schnell J, Bruecher D, Knapp S, Vogler M

Cell Commun Signal. 22(1):415. doi: 10.1186/s12964-024-01782-9

Publication date: August 27, 2024

PMID: 39192247

A guide to selecting high-performing antibodies for Synaptotagmin-1 (Uniprot ID P21579) for use in western blot, immunoprecipitation, immunofluorescence and flow cytometry.

Biddle MS, Alende C, Fotouhi M, Jones C, Ayoubi R, Southern K, Laflamme C, Virk H

F1000Res. 13:817. doi: 10.12688/f1000research.154034.1

Publication date: August 22, 2024

PMID: 39169954

A chemical screen identifies PRMT5 as a therapeutic vulnerability for paclitaxel-resistant triple-negative breast cancer.

Zhang K, Wei J, Zhang S, Fei L, Guo L, Liu X, Ji Y, Chen W, Ciamponi FE, Chen W, Li M, Zhai J, Fu T, Massirer KB, Yu Y, Lupien M, Wei Y, Arrowsmith CH, Wu Q, Tan W

Cell Chem Biol. doi: 10.1016/j.chembiol.2024.08.003

Publication date: August 21, 2024

PMID: 39232499

Chemical coverage of human biological pathways.

Angela Kwak H, Liu L, Tredup C, Röhm S, Prinos P, Böttcher J, Schapira M

Drug Discov Today. 104144. doi: 10.1016/j.drudis.2024.104144

Publication date: August 21, 2024

PMID: 39179147

Screening of a kinase inhibitor library identified novel targetable kinase pathways in triple-negative breast cancer.

Rinderle CH, Baker CV, Lagarde CB, Nguyen K, Al-Ghadban S, Matossian MD, Hoang VT, Martin EC, Collins-Burow BM, Ali S, Drewry DH, Burow ME, Bunnell BA

Anticancer Drugs. doi: 10.1097/CAD.0000000000001658

Publication date: August 21, 2024

PMID: 39163320

Antibody characterization is critical to enhance reproducibility in biomedical research.

Kahn RA, Virk H, Laflamme C, Houston DW, Polinski NK, Meijers R, Levey AI, Saper CB, Errington TM, Turn RE, Bandrowski A, Trimmer JS, Rego M, Freedman LP, Ferrara F, Bradbury ARM, Cable H, Longworth S

Elife. 13:. doi: 10.7554/eLife.100211

Publication date: August 14, 2024

PMID: 39140332

Benchmarking Methods for PROTAC Ternary Complex Structure Prediction.

Rovers E, Schapira M

J Chem Inf Model. 64(15):6162-6173. doi: 10.1021/acs.jcim.4c00426

Publication date: August 12, 2024

PMID: 39087481

Discovery and Characterization of a Chemical Probe for Cyclin-Dependent Kinase-Like 2.

Bashore FM, Min SM, Chen X, Howell S, Rinderle CH, Morel G, Silvaroli JA, Wells CI, Bunnell BA, Drewry DH, Pabla NS, Ultanir SK, Bullock AN, Axtman AD

ACS Med Chem Lett. 15(8):1325-1333. doi: 10.1021/acsmedchemlett.4c00219

Publication date: August 8, 2024

PMID: 39140040

High-Throughput Screening for LC3/GABARAP Binders Utilizing the Fluorescence Polarization Assay.

Schwalm MP, Dopfer J, Knapp S, Rogov VV

Methods Mol Biol. 2845:203-218. doi: 10.1007/978-1-0716-4067-8_17

Publication date: August 8, 2024

PMID: 39115669

Thermodynamic Characterization of LC3/GABARAP:Ligand Interactions by Isothermal Titration Calorimetry.

Dopfer J, Schwalm MP, Knapp S, Rogov VV

Methods Mol Biol. 2845:219-235. doi: 10.1007/978-1-0716-4067-8_18

Publication date: August 8, 2024

PMID: 39115670

A guide to selecting high-performing antibodies for human Midkine for use in Western blot and immunoprecipitation.

Ayoubi R, Southern K, Laflamme C

F1000Res. 12:148. doi: 10.12688/f1000research.130587.3

Publication date: August 2, 2024

PMID: 39092005

Quantitative Hydrogen-Deuterium Exchange Mass Spectrometry for Simultaneous Structural Characterization and Affinity Indexing of Single Target Drug Candidate Libraries.

Wolf E, Herasymenko O, Kutera M, Lento C, Arrowsmith C, Ackloo S, Wilson D

Anal Chem. doi: 10.1021/acs.analchem.4c01001

Publication date: July 29, 2024

PMID: 39074309

A ligand discovery toolbox for the WWE domain family of human E3 ligases.

Münzker L, Kimani SW, Fowkes MM, Dong A, Zheng H, Li Y, Dasovich M, Zak KM, Leung AKL, Elkins JM, Kessler D, Arrowsmith CH, Halabelian L, Böttcher J

Commun Biol. 7(1):901. doi: 10.1038/s42003-024-06584-w

Publication date: July 24, 2024

PMID: 39048679

A high-throughput approach to identify BRCA1-downregulating compounds to enhance PARP inhibitor sensitivity.

Sellars E, Savguira M, Wu J, Cancelliere S, Jen M, Krishnan R, Hakem A, Barsyte-Lovejoy D, Hakem R, Narod SA, Kotsopoulos J, Salmena L

iScience. 27(7):110180. doi: 10.1016/j.isci.2024.110180

Publication date: July 19, 2024

PMID: 38993666

Back-Pocket Optimization of 2-Aminopyrimidine-Based Macrocycles Leads to Potent EPHA2/GAK Kinase Inhibitors.

Gerninghaus J, Zhubi R, Krämer A, Karim M, Tran DHN, Joerger AC, Schreiber C, Berger LM, Berger BT, Ehret TAL, Elson L, Lenz C, Saxena K, Müller S, Einav S, Knapp S, Hanke T

J Med Chem. doi: 10.1021/acs.jmedchem.4c00411

Publication date: July 19, 2024

PMID: 39028937

Huntingtin is an RNA binding protein and participates in NEAT1-mediated paraspeckles.

Yadav M, Harding RJ, Li T, Xu X, Gall-Duncan T, Khan M, Bardile CF, Sequiera GL, Duan S, Chandrasekaran R, Pan A, Bu J, Yamazaki T, Hirose T, Prinos P, Tippett L, Turner C, Curtis MA, Faull RLM, Pouladi MA, Pearson CE, He HH, Arrowsmith CH

Sci Adv. 10(29):eado5264. doi: 10.1126/sciadv.ado5264

Publication date: July 19, 2024

PMID: 39028820

Discovery of Two Highly Selective Structurally Orthogonal Chemical Probes for Activin Receptor-like Kinases 1 and 2.

Němec V, Remeš M, Beňovský P, Böck MC, Šranková E, Wong JF, Cros J, Williams E, Tse LH, Smil D, Ensan D, Isaac MB, Al-Awar R, Gomolková R, Ursachi VC, Fafílek B, Kahounová Z, Víchová R, Vacek O, Berger BT, Wells CI, Corona CR, Vasta JD, Robers MB, Krejci P, Souček K, Bullock AN, Knapp S, Paruch K

J Med Chem. doi: 10.1021/acs.jmedchem.4c00629

Publication date: July 18, 2024

PMID: 39023313

The identification of high-performing antibodies for Sequestosome-1 for use in Western blot, immunoprecipitation and immunofluorescence.

Ayoubi R, Alshafie W, Shlaifer I, Southern K, McPherson PS, Laflamme C

F1000Res. 12:324. doi: 10.12688/f1000research.132628.2

Publication date: July 15, 2024

PMID: 39006307

Synthesis and evaluation of chemical linchpins for highly selective CK2α targeting.

Greco FA, Krämer A, Wahl L, Elson L, Ehret TAL, Gerninghaus J, Möckel J, Müller S, Hanke T, Knapp S

Eur J Med Chem. 276:116672. doi: 10.1016/j.ejmech.2024.116672

Publication date: July 14, 2024

PMID: 39067440

A guide to selecting high-performing antibodies for Rab1A and Rab1B for use in Western Blot, immunoprecipitation and immunofluorescence.

Ruíz Moleón V, Fotouhi M, Ayoubi R, González Bolívar S, Southern K, McPherson PS, Laflamme C

F1000Res. 12:1578. doi: 10.12688/f1000research.143928.2

Publication date: July 11, 2024

PMID: 38559361

A guide to selecting high-performing antibodies for RNA-binding protein TIA1 for use in Western Blot, immunoprecipitation and immunofluorescence.

Fotouhi M, Worrall D, Ayoubi R, Southern K, McPherson PS, Laflamme C

F1000Res. 12:745. doi: 10.12688/f1000research.133645.2

Publication date: July 11, 2024

PMID: 38638178

Characterization of covalent inhibitors that disrupt the interaction between the tandem SH2 domains of SYK and FCER1G phospho-ITAM.

Bashore FM, Katis VL, Du Y, Sikdar A, Wang D, Bradshaw WJ, Rygiel KA, Leisner TM, Chalk R, Mishra S, Williams CA, Gileadi O, Brennan PE, Wiley JC, Gockley J, Cary GA, Carter GW, Young JE, Pearce KH, Fu H, Axtman AD

PLoS One. 19(2):e0293548. doi: 10.1371/journal.pone.0293548

Publication date: July 11, 2024

PMID: 38359047