Publications

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2025

Phenomics-based Discovery of Novel Orthosteric Choline Kinase Inhibitors.

Bauer LG, Ward JA, Díaz-Sáez L, Sundström Y, Tolvanen T, Barrera JCA, Kostidis S, Rogers CM, Panagakou I, Singh U, Rothweiler EM, Gonzalez Orta A, Kaniskan HÜ, Hu J, Jin J, Sievers S, Waldmann H, Giera M, Sundström M, Berg L, Huber K

Angew Chem Int Ed Engl. e202420149. doi: 10.1002/anie.202420149

Publication date: January 1, 2025

PMID: 39740997

2024

Development and Discovery of a Selective Degrader of Casein Kinases 1 δ/ε.

Haag A, Němec V, Janovská P, Bartošíková J, Adhikari B, Müller J, Schwalm MP, Čada Š, Ohmayer U, Daub H, Kim Y, Born F, Wolf E, Bryja V, Knapp S

J Med Chem. doi: 10.1021/acs.jmedchem.4c02201

Publication date: December 27, 2024

PMID: 39729064

Targeting Na(v)1.7 and Na(v)1.8 with a PIKfyve inhibitor to reverse inflammatory and neuropathic pain.

Rodríguez-Palma EJ, Loya-Lopez S, Min SM, Calderon-Rivera A, Gomez K, Khanna R, Axtman AD

Neurobiol Pain. 17:100174. doi: 10.1016/j.ynpai.2024.100174

Publication date: December 25, 2024

PMID: 39720155

Probing the Protein Kinases' Cysteinome by Covalent Fragments.

Wang G, Seidler NJ, Röhm S, Pan Y, Liang XJ, Haarer L, Berger BT, Sivashanmugam SA, Wydra VR, Forster M, Laufer SA, Chaikuad A, Gehringer M, Knapp S

Angew Chem Int Ed Engl. e202419736. doi: 10.1002/anie.202419736

Publication date: December 24, 2024

PMID: 39716901

Interplay between β-propeller subunits WDR26 and muskelin regulates the CTLH E3 ligase supramolecular complex.

Maitland MER, Onea G, Owens DDG, Gonga-Cavé BC, Wang X, Arrowsmith CH, Barsyte-Lovejoy D, Lajoie GA, Schild-Poulter C

Commun Biol. 7(1):1668. doi: 10.1038/s42003-024-07371-3

Publication date: December 20, 2024

PMID: 39702571

DARPins as a novel tool to detect and degrade p73.

Münick P, Zielinski J, Strubel A, Gutfreund N, Dreier B, Schaefer JV, Schäfer B, Gebel J, Osterburg C, Chaikuad A, Knapp S, Plückthun A, Dötsch V

Cell Death Dis. 15(12):909. doi: 10.1038/s41419-024-07304-2

Publication date: December 19, 2024

PMID: 39695090

A consensus platform for antibody characterization.

Ayoubi R, Ryan J, Gonzalez Bolivar S, Alende C, Ruiz Moleon V, Fotouhi M, Alqazzaz M, Southern K, Alshafie W, Baker MR, Ball AR Jr, Callahan D, Cooper JA, Crosby K, Harvey KJ, Houston DW, Kumaran R, Rego M, Schofield C, Wu H, Biddle MS, Brown CM, Kahn RA, Bandrowski A, Virk HS, Edwards AM, McPherson PS, Laflamme C

Nat Protoc. doi: 10.1038/s41596-024-01095-8

Publication date: December 18, 2024

PMID: 39690206

Design, Synthesis, and Biochemical Evaluation of Novel MLK3 Inhibitors: A Target Hopping Example.

Sander P, Schwalm MP, Krämer A, Elson L, Rasch A, Masberg B, Selig R, Sievers-Engler A, Lämmerhofer M, Müller S, Knapp S, Albrecht W, Laufer SA

J Med Chem. doi: 10.1021/acs.jmedchem.4c02552

Publication date: December 17, 2024

PMID: 39681301

Probe my Pathway (PmP): a portal to explore the chemical coverage of the human Reactome.

Kwak HA, Liu L, Schapira M

Database (Oxford). 2024:. doi: 10.1093/database/baae116

Publication date: December 15, 2024

PMID: 39657145

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. 36(1):39-48. doi: 10.1097/CAD.0000000000001658

Publication date: December 13, 2024

PMID: 39671264

A Covalent Chemical Probe for Chikungunya nsP2 Cysteine Protease with Antialphaviral Activity and Proteome-wide Selectivity.

Ghoshal A, Tse EG, Hossain MA, Asressu KH, Merten EM, Sears JD, Howell S, Perveen S, Burdick J, Morales NL, Martinez SA, Law I, Davenport BJ, Morrison TE, Streblow ZJ, Streblow DN, Mordant AL, Webb TS, Cabrera A, Herring LE, Arrowsmith CH, Pearce KH, Moorman NJ, Heise MT, Couñago RM, Brown PJ, Willson TM

Res Sq. doi: 10.21203/rs.3.rs-5363451/v1

Publication date: November 28, 2024

PMID: 39606462

Critical assessment of LC3/GABARAP ligands used for degrader development and ligandability of LC3/GABARAP binding pockets.

Schwalm MP, Dopfer J, Kumar A, Greco FA, Bauer N, Löhr F, Heering J, Cano-Franco S, Lechner S, Hanke T, Jaser I, Morasch V, Lenz C, Fearon D, Marples PG, Tomlinson CWE, Brunello L, Saxena K, Adams NBP, von Delft F, Müller S, Stolz A, Proschak E, Kuster B, Knapp S, Rogov VV

Nat Commun. 15(1):10204. doi: 10.1038/s41467-024-54409-5

Publication date: November 26, 2024

PMID: 39587067

Crystal structures of DCAF1-PROTAC-WDR5 ternary complexes provide insight into DCAF1 substrate specificity.

Mabanglo MF, Wilson B, Noureldin M, Kimani SW, Mamai A, Krausser C, González-Álvarez H, Srivastava S, Mohammed M, Hoffer L, Chan M, Avrumutsoae J, Li ASM, Hajian T, Tucker S, Green S, Szewczyk M, Barsyte-Lovejoy D, Santhakumar V, Ackloo S, Loppnau P, Li Y, Seitova A, Kiyota T, Wang JG, Privé GG, Kuntz DA, Patel B, Rathod V, Vala A, Rout B, Aman A, Poda G, Uehling D, Ramnauth J, Halabelian L, Marcellus R, Al-Awar R, Vedadi M

Nat Commun. 15(1):10165. doi: 10.1038/s41467-024-54500-x

Publication date: November 24, 2024

PMID: 39580491

The endocannabinoid anandamide mediates anti-inflammatory effects through activation of NR4A nuclear receptors.

Teichmann T, Pflüger-Müller B, Giménez VMM, Sailer F, Dirks H, Zehr S, Warwick T, Brettner F, Munoz-Tello P, Zimmer A, Tegeder I, Thomas D, Gurke R, Günther S, Heering J, Proschak E, Geisslinger G, Bibli IS, Heringdorf DMZ, Manucha W, Windbergs M, Knapp S, Weigert A, Leisegang MS, Kojetin D, Brandes RP

Br J Pharmacol. doi: 10.1111/bph.17366

Publication date: November 20, 2024

PMID: 39563075

The Chemical Probes Portal - 2024: update on this public resource to support best-practice selection and use of small molecules in biomedical research.

Sanfelice D, Antolin AA, Crisp A, Chen Y, Bellenie B, Brennan PE, Edwards A, Müller S, Al-Lazikani B, Workman P

Nucleic Acids Res. doi: 10.1093/nar/gkae1062

Publication date: November 19, 2024

PMID: 39558166

Discovery of CHD1 Antagonists for PTEN-Deficient Prostate Cancer.

Johnson RL, Graboski AL, Li F, Norris-Drouin JL, Walton WG, Arrowsmith CH, Redinbo MR, Frye SV, James LI

J Med Chem. doi: 10.1021/acs.jmedchem.4c01172

Publication date: November 13, 2024

PMID: 39508435

CACHE Challenge #1: Targeting the WDR Domain of LRRK2, A Parkinson's Disease Associated Protein.

Li F, Ackloo S, Arrowsmith CH, Ban F, Barden CJ, Beck H, Beránek J, Berenger F, Bolotokova A, Bret G, Breznik M, Carosati E, Chau I, Chen Y, Cherkasov A, Corte DD, Denzinger K, Dong A, Draga S, Dunn I, Edfeldt K, Edwards A, Eguida M, Eisenhuth P, Friedrich L, Fuerll A, Gardiner SS, Gentile F, Ghiabi P, Gibson E, Glavatskikh M, Gorgulla C, Guenther J, Gunnarsson A, Gusev F, Gutkin E, Halabelian L, Harding RJ, Hillisch A, Hoffer L, Hogner A, Houliston S, Irwin JJ, Isayev O, Ivanova A, Jacquemard C, Jarrett AJ, Jensen JH, Kireev D, Kleber J, Koby SB, Koes D, Kumar A, Kurnikova MG, Kutlushina A, Lessel U, Liessmann F, Liu S, Lu W, Meiler J, Mettu A, Minibaeva G, Moretti R, Morris CJ, Narangoda C, Noonan T, Obendorf L, Pach S, Pandit A, Perveen S, Poda G, Polishchuk P, Puls K, Pütter V, Rognan D, Roskams-Edris D, Schindler C, Sindt F, Spiwok V, Steinmann C, Stevens RL, Talagayev V, Tingey D, Vu O, Walters WP, Wang X, Wang Z, Wolber G, Wolf CA, Wortmann L, Zeng H, Zepeda CA, Zhang KYJ, Zhang J, Zheng S, Schapira M

J Chem Inf Model. doi: 10.1021/acs.jcim.4c01267

Publication date: November 5, 2024

PMID: 39499532

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

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

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

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