Publications | Structural Genomics Consortium

Kimani SW, Noureldin M, Wilson B, Hoffer L, Green SR, Szewczyk MM, González-Álvarez H, Mohammed M, Chan M, Krausser C, Li ASM, Hajian T, Tucker S, Joshi D, Saraon P, Thériault B, Kim JS, Santhakumar V, Loppnau P, Li Y, Seitova A, Dong A, Kiyota T, Hammann T, Gehrtz P, Patel B, Rathod V, Vala A, Rout B, Jagodra P, Brown PJ, Aman A, Ramnauth J, Poda G, Uehling D, Arrowsmith CH, Barsyte-Lovejoy D, Marcellus R, Ackloo S, Mamai A, Al-Awar R, Halabelian L

Commun Biol. 8(1):1076. doi: 10.1038/s42003-025-08491-0

Publication date: July 20, 2025

PMID: 40683980

Enantioselective Chemical Probe for Chikungunya nsP2 Helicase with Antialphaviral Activity.

Muthu Ramalingam B, Oh HJ, Sears JD, Chen CH, Vala A, Liu S, Talbot KM, Hossain MA, Brown PJ, Houliston S, Garcia Perez J, Li F, Amare MG, Halfmann P, Smith JL, Hirsch AJ, Arrowsmith CH, Halabelian L, Vargason A, Couñago RM, Arnold JJ, Cameron CE, Moorman NJ, Heise MT, Willson TM

ACS Infect Dis. doi: 10.1021/acsinfecdis.5c00351

Publication date: July 18, 2025

PMID: 40680191

Exploring the Ligandability of 53BP1 through Fragment-Based Approaches.

Chiew B, Gunzburg MJ, Foley CA, Zeng H, Dong A, Brown PJ, The J, Norris-Drouin JL, Cholensky SH, Mohanty B, Scanlon MJ, Headey SJ, Doak BC, James LI

ACS Med Chem Lett. 16(7):1290-1298. doi: 10.1021/acsmedchemlett.5c00125

Publication date: July 16, 2025

PMID: 40666473

A guide to selecting high-performing antibodies for Stearoyl-CoA desaturase (SCD1) (UniProt ID: O00767) for use in western blot, immunoprecipitation, and immunofluorescence.

Ruíz Moleón V, Alende C, Fotouhi M, González Bolívar S, Ayoubi R, Laflamme C

F1000Res. 14:10. doi: 10.12688/f1000research.160217.2

Publication date: July 14, 2025

PMID: 40657179

Identification of Direct-Acting nsP2 Helicase Inhibitors with Antialphaviral Activity.

Muthu Ramalingam B, Sears JD, Talbot KM, Su YN, Houliston S, Hossain MA, Davis-Gilbert ZW, Zhao C, Oh HJ, Brown PJ, Sanders MK, Moorman SR, Ojha D, Burdick JE, Law I, Morales NL, Martinez SA, Loppnau P, Garcia Perez J, Drobish AM, Morrison TE, Streblow ZJ, Streblow DN, Arrowsmith CH, Vargason A, Couñago RM, Halabelian L, Arnold JJ, Cameron CE, Moorman NJ, Heise MT, Willson TM

J Med Chem. doi: 10.1021/acs.jmedchem.5c00635

Publication date: July 10, 2025

PMID: 40634283

Activation of endogenous PRKN by structural derepression is linked to increased turnover of the E3 ubiquitin ligase.

Fiesel F, Bustillos B, Watzlawik J, Chen C, Berryer M, Zhang J, Boneski P, Hayes C, Bredenberg J, Deneault E, You Z, Abdien N, Aprahamian N, Goldsmith T, Baninameh Z, Cocker L, Zhang H, Goldberg M, Fon E, Trempe JF, Virdee S, Durcan T, Springer W

Autophagy. doi: 10.1080/15548627.2025.2531025

Publication date: July 8, 2025

PMID: 40624741

Covalent Targeting Leads to the Development of a LIMK1 Isoform-Selective Inhibitor.

Mandel S, Hanke T, Prendiville N, Baena-Nuevo M, Berger LM, Farges F, Schwalm MP, Berger BT, Kraemer A, Elson L, Saraswati H, Abdul Azeez KR, Dederer V, Mathea S, Corrionero A, Alfonso P, Keller S, Gstaiger M, Krause DS, Müller S, Röhm S, Knapp S

J Med Chem. doi: 10.1021/acs.jmedchem.5c01204

Publication date: July 2, 2025

PMID: 40598933

CACHE Challenge #2: Targeting the RNA Site of the SARS-CoV-2 Helicase Nsp13.

Herasymenko O, Silva M, Abu-Saleh AAA, Ahmad A, Alvarado-Huayhuaz J, Arce OEA, Armstrong RJ, Arrowsmith C, Bachta KE, Beck H, Berta D, Bieniek MK, Blay V, Bolotokova A, Bourne PE, Breznik M, Brown PJ, Campbell ADG, Carosati E, Chau I, Cole DJ, Cree B, Dehaen W, Denzinger K, Dos Santos Machado K, Dunn I, Durai P, Edfeldt K, Edwards A, Fayne D, Felfoldi D, Friston K, Ghiabi P, Gibson E, Günther J, Gunnarsson A, Hillisch A, Houston DR, Jensen JH, Harding RJ, Harris KS, Hoffer L, Hogner A, Horton JT, Houliston S, Hultquist JF, Hutchinson A, Irwin JJ, Jukič M, Kandwal S, Karlova A, Katis VL, Kich RP, Kireev D, Koes D, Inniss NL, Lessel U, Liu S, Loppnau P, Lu W, Martino S, McGibbon M, Meiler J, Mettu A, Money-Kyrle S, Moretti R, Moroz YS, Muvva C, Newman JA, Obendorf L, Paige B, Pandit A, Park K, Perveen S, Pirie R, Poda G, Protopopov M, Pütter V, Ricci F, Roper NJ, Rosta E, Rzhetskaya M, Sabnis Y, Satchell KJF, Schmitt Kremer F, Scott T, Seitova A, Steinmann C, Talagayev V, Tarkhanova OO, Tatum NJ, Treleaven D, Velasque Werhli A, Walters WP, Wang X, Wells J, Wells G, Westermaier Y, Wolber G, Wortmann L, Zhang J, Zhao Z, Zheng S, Schapira M

J Chem Inf Model. doi: 10.1021/acs.jcim.5c00535

Publication date: June 20, 2025

PMID: 40539604

A guide to selecting high-performing antibodies for Rab10 (UniProt ID: P61026) for use in western blot, immunoprecipitation, and immunofluorescence.

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

F1000Res. 13:1061. doi: 10.12688/f1000research.156209.1

Publication date: June 19, 2025

PMID: 40535172

A guide to selecting high-performing antibodies for STING1 (Uniprot ID: Q86WV6) for use in western blot, immunoprecipitation, and immunofluorescence.

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

F1000Res. 13:1049. doi: 10.12688/f1000research.155929.2

Publication date: June 19, 2025

PMID: 40535171

Structure-Based Design of PROTACS for the Degradation of Soluble Epoxide Hydrolase.

Schönfeld J, Brunst S, Ciomirtan L, Willmer L, Chromik MA, Kumar A, Froemel T, Liebisch N, Hackspacher A, Ehrler JHM, Wintermeier L, Hesse C, Fiedler J, Heering J, Freitag H, Zardo P, Fieguth HG, Brüggerhoff A, Jakob J, Häupl B, Weizel L, Kaiser A, Schubert-Zsilavecz M, Oellerich T, Fleming I, Schebb NH, Fürst R, Kannt A, Knapp S, Proschak E, Hiesinger K

J Med Chem. doi: 10.1021/acs.jmedchem.5c00552

Publication date: June 18, 2025

PMID: 40532036

Crystallographic fragment screening reveals ligand hotspots in TRIM21 PRY-SPRY domain.

Kim Y, Lučić A, Lenz C, Farges F, Schwalm MP, Saxena K, Hanke T, Marples PG, Aschenbrenner JC, Fearon D, von Delft F, Krämer A, Knapp S

Commun Chem. 8(1):185. doi: 10.1038/s42004-025-01574-3

Publication date: June 14, 2025

PMID: 40514378

Type II kinase inhibitors that target Parkinson's disease-associated LRRK2.

Raig ND, Surridge KJ, Sanz-Murillo M, Dederer V, Krämer A, Schwalm MP, Lattal NM, Elson L, Chatterjee D, Mathea S, Hanke T, Leschziner AE, Reck-Peterson SL, Knapp S

Sci Adv. 11(23):eadt2050. doi: 10.1126/sciadv.adt2050

Publication date: June 4, 2025

PMID: 40465731

Active Learning-Guided Hit Optimization for the Leucine-Rich Repeat Kinase 2 WDR Domain Based on In Silico Ligand-Binding Affinities.

Gusev F, Gutkin E, Gentile F, Ban F, Koby SB, Li F, Chau I, Ackloo S, Arrowsmith CH, Bolotokova A, Ghiabi P, Gibson E, Halabelian L, Houliston S, Harding RJ, Hutchinson A, Loppnau P, Perveen S, Seitova A, Zeng H, Schapira M, Cherkasov A, Isayev O, Kurnikova MG

J Chem Inf Model. doi: 10.1021/acs.jcim.5c00588

Publication date: May 26, 2025

PMID: 40415386

PRMT1 inhibitor MS023 suppresses RNA splicing to sensitize small cell lung cancer to DNA damaging agents.

Aparnathi MK, Ul Haq S, St-Germain J, Nixon KCJ, Walton J, Song L, Majeed S, Patel PS, Subramaniam R, Philip V, Marcellus R, Barsyte-Lovejoy D, Al-Awar R, Hakem R, Arrowsmith CH, Ailles L, Raught B, Lok BH

Neoplasia. 66:101176. doi: 10.1016/j.neo.2025.101176

Publication date: May 26, 2025

PMID: 40413955

Species-Dependent Metabolism of a Covalent nsP2 Protease Inhibitor with In Vivo Antialphaviral Activity.

Hossain MA, Mayo AK, Ghoshal A, Taft-Benz S, Anderson E, Morales NL, Pressey KD, Vargason A, Brouwer KLR, Moorman NJ, Heise MT, Willson TM

J Med Chem. doi: 10.1021/acs.jmedchem.5c00825

Publication date: May 12, 2025

PMID: 40351160

Structural basis of TMPRSS11D specificity and autocleavage activation.

Fraser BJ, Wilson RP, Ferková S, Ilyassov O, Lac J, Dong A, Li YY, Seitova A, Li Y, Hejazi Z, Kenney TMG, Penn LZ, Edwards A, Leduc R, Boudreault PL, Morin GB, Bénard F, Arrowsmith CH

Nat Commun. 16(1):4351. doi: 10.1038/s41467-025-59677-3

Publication date: May 11, 2025

PMID: 40348740

Biochemical investigation of LC3/GABARAP-ligand interaction as an important quality measure for LC3/GABARAP-targeting small molecules: addendum to the guidelines (4th edition).

Schwalm MP, Lenz C, Saxena K, Klionsky DJ, Proschak E, Knapp S

Autophagy. 1-5. doi: 10.1080/15548627.2025.2498506

Publication date: May 9, 2025

PMID: 40344429

Broad Target Screening Reveals Abundance of FKBP12-Based Molecular Glues in Focused Libraries.

Dreizler JK, Meyners C, Sugiarto WO, Repity ML, Maciel EVS, Purder PL, Lermyte F, Knapp S, Hausch F

J Med Chem. 68(9):9525-9536. doi: 10.1021/acs.jmedchem.5c00220

Publication date: May 8, 2025

PMID: 40336336

Native Taylor/Non-Taylor Dispersion-Mass Spectrometry (TNT-MS) Allows Rapid Protein Desalting and Multiplexed, Label-Free Ligand Screening.

Eisert J, Maciel EVS, Dederer V, Berwanger A, Bailey HJ, Đikić I, Knapp S, Empting M, Mathea S, Jensen H, Lermyte F

Small Methods. e2500658. doi: 10.1002/smtd.202500658

Publication date: May 7, 2025

PMID: 40331427

Native Flow-Induced Dispersion Analysis - Mass Spectrometry Enables Automated, Multiplexed Ligand Screening from Conventional, Nonvolatile Buffers.

Maciel EVS, Eisert J, Dederer V, Berwanger A, Knapp S, Empting M, Mathea S, Jensen H, Lermyte F

Anal Chem. doi: 10.1021/acs.analchem.5c00696

Publication date: May 5, 2025

PMID: 40324204

Chemical arsenal for helicase Hunters: Striking the toughest targets in antiviral research.

Martin HJ, Hossain MA, Wellnitz J, Kelestemur E, Hochuli JE, Perveen S, Arrowsmith C, Willson TM, Muratov EN, Tropsha A

Antiviral Res. 239:106184. doi: 10.1016/j.antiviral.2025.106184

Publication date: May 3, 2025

PMID: 40316178

PRMT5 promotes full-length HTT expression by repressing multiple proximal intronic polyadenylation sites.

Yadav M, AlQazzaz MA, Ciamponi FE, Ho JC, Maron MI, Sababi AM, MacLeod G, Ahmadi M, Bullivant G, Tano V, Langley SR, Sánchez-Osuna M, Sachamitr P, Kushida M, Bardile CF, Pouladi MA, Kurtz R, Richards L, Pugh T, Tyers M, Angers S, Dirks PB, Bader GD, Truant R, Massirer KB, Barsyte-Lovejoy D, Shechter D, Harding RJ, Arrowsmith CH, Prinos P

Nucleic Acids Res. 53(8):. doi: 10.1093/nar/gkaf347

Publication date: April 30, 2025

PMID: 40304179

A guide to selecting high-performing antibodies for S1PR1 (UniProt ID: P21453) for use in western blot, immunoprecipitation, and immunofluorescence.

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

F1000Res. 13:792. doi: 10.12688/f1000research.153244.2

Publication date: April 28, 2025

PMID: 40291769

Challenges and advances for huntingtin detection in cerebrospinal fluid: in support of relative quantification.

Harding RJ, Xie Y, Caron NS, Findlay-Black H, Lyu C, Potluri N, Chandrasekaran R, Hayden MR, Leavitt BR, Langbehn DR, Southwell AL

Biomark Res. 13(1):63. doi: 10.1186/s40364-025-00772-4

Publication date: April 22, 2025

PMID: 40259428

Structure-Guided Design of ISOX-DUAL-Based Degraders Targeting BRD4 and CBP/EP300: A Case of Degrader Collapse.

Edmonds AK, Balourdas DI, Marsh GP, Felix R, Brasher B, Cooper J, Graber-Feesl C, Kollareddy M, Malik K, Stewart H, Chevassut TJT, Lineham E, Morley S, Fedorov O, Bennett J, Rajasekaran MB, Ojeda S, Harrison DA, Ott CJ, Joerger AC, Maple HJ, Spencer J

J Med Chem. doi: 10.1021/acs.jmedchem.5c00395

Publication date: April 17, 2025

PMID: 40244695

Repurposing of the RIPK1-Selective Benzo[1,4]oxazepin-4-one Scaffold for the Development of a Type III LIMK1/2 Inhibitor.

Mandel S, Hanke T, Mathea S, Chatterjee D, Saraswati H, Berger BT, Schwalm MP, Yamamoto S, Tawada M, Takagi T, Ahmed M, Röhm S, Corrionero A, Alfonso P, Baena M, Elson L, Menge A, Krämer A, Pereira R, Müller S, Krause DS, Knapp S

ACS Chem Biol. doi: 10.1021/acschembio.5c00097

Publication date: April 14, 2025

PMID: 40227881

ATPase activity profiling of three human DExD/H-box RNA helicases.

Li F, Chan UH, Perez JG, Zeng H, Chau I, Li Y, Seitova A, Halabelian L

SLAS Discov. 32:100229. doi: 10.1016/j.slasd.2025.100229

Publication date: April 8, 2025

PMID: 40194700

A guide to selecting high-performing antibodies for TAF15 (UniProt ID: Q92804) for use in western blot, immunoprecipitation, and immunofluorescence.

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

F1000Res. 14:37. doi: 10.12688/f1000research.160371.1

Publication date: April 4, 2025

PMID: 40182019

From N-0385 to N-0920: Unveiling a Host-Directed Protease Inhibitor with Picomolar Antiviral Efficacy against Prevalent SARS-CoV-2 Variants.

Lemieux G, Pérez-Vargas J, Désilets A, Hassanzadeh M, Thompson CAH, Gravel-Trudeau A, Joushomme A, Ennis S, Villanueva I, Marouseau É, Fraser BJ, Champagne W, Lepage M, Niikura M, Arrowsmith CH, Jean F, Leduc R, Boudreault PL

J Med Chem. doi: 10.1021/acs.jmedchem.4c02468

Publication date: March 31, 2025

PMID: 40163818

Chemoproteomic Profiling of C. albicans for Characterization of Antifungal Kinase Inhibitors.

Shirley DJ, Nandakumar M, Cabrera A, Yiu B, Puumala E, Liu Z, Robbins N, Whitesell L, Smith JL, Lyons S, Mordant AL, Herring LE, Graves LM, Couñago RM, Drewry DH, Cowen LE, Willson TM

J Med Chem. doi: 10.1021/acs.jmedchem.5c00097

Publication date: March 20, 2025

PMID: 40110855

Structure-guided optimization of small molecules targeting Yck2 as a strategy to combat Candida albicans.

Puumala E, Nandakumar M, Yiu B, Stogios PJ, Strickland BG, Zarnowski R, Wang X, Williams NS, Savchenko A, Andes DR, Robbins N, Whitesell L, Willson TM, Cowen LE

Nat Commun. 16(1):2156. doi: 10.1038/s41467-025-57346-z

Publication date: March 5, 2025

PMID: 40038303

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

Sci Rep. 15(1):7264. doi: 10.1038/s41598-025-91673-x

Publication date: March 3, 2025

PMID: 40025188

A guide to selecting high-performing antibodies for CSNK1A1 (UniProt ID: P48729) for use in western blot, immunoprecipitation, and immunofluorescence.

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

F1000Res. 13:1055. doi: 10.12688/f1000research.155928.1

Publication date: March 3, 2025

PMID: 40028451

Probing cancer with small-molecule tools-Progress and challenges.

Müller S, Sanfelice D, Workman P

Cancer Cell. doi: 10.1016/j.ccell.2025.02.003

Publication date: March 1, 2025

PMID: 40020670

Potent and selective SETDB1 covalent negative allosteric modulator reduces methyltransferase activity in cells.

Uguen M, Shell DJ, Silva M, Deng Y, Li F, Szewczyk MM, Yang K, Zhao Y, Stashko MA, Norris-Drouin JL, Waybright JM, Beldar S, Rectenwald JM, Mordant AL, Webb TS, Herring LE, Arrowsmith CH, Ackloo S, Gygi SP, McGinty RK, Barsyte-Lovejoy D, Liu P, Halabelian L, James LI, Pearce KH, Frye SV

Nat Commun. 16(1):1905. doi: 10.1038/s41467-025-57005-3

Publication date: February 25, 2025

PMID: 39994194

Revisiting huntingtin activity and localization signals in the context of protein structure.

Truant R, Harding RJ, Neuman K, Maiuri T

J Huntingtons Dis. 13(4):419-430. doi: 10.1177/18796397241295303

Publication date: February 20, 2025

PMID: 39973382

Structural insights into human brachyury DNA recognition and discovery of progressible binders for cancer therapy.

Newman JA, Gavard AE, Imprachim N, Aitkenhead H, Sheppard HE, Te Poele R, Clarke PA, Hossain MA, Temme L, Oh HJ, Wells CI, Davis-Gilbert ZW, Workman P, Gileadi O, Drewry DH

Nat Commun. 16(1):1596. doi: 10.1038/s41467-025-56213-1

Publication date: February 15, 2025

PMID: 39952925

A guide to selecting high-performing antibodies for ADNP (UniProt ID: Q9H2P0) for use in western blot, immunoprecipitation, and immunofluorescence.

Ruíz Moleón V, Alende C, Fotouhi M, Ayoubi R, González Bolívar S, Laflamme C

F1000Res. 13:1545. doi: 10.12688/f1000research.160121.1

Publication date: February 14, 2025

PMID: 39949964

The Need for Continuing Blinded Pose- and Activity Prediction Benchmarks.

Kramer C, Chodera J, Damm-Ganamet KL, Gilson MK, Günther J, Lessel U, Lewis RA, Mobley D, Nittinger E, Pecina A, Schapira M, Walters WP

J Chem Inf Model. doi: 10.1021/acs.jcim.4c02296

Publication date: February 14, 2025

PMID: 39951479

A guide to selecting high-performing antibodies for Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform (PPP2R5D) for use in Western Blot, immunoprecipitation and immunofluorescence.

Ayoubi R, Fotouhi M, Alende C, Southern K, Laflamme C

F1000Res. 13:1. doi: 10.12688/f1000research.145146.2

Publication date: February 12, 2025

PMID: 39935523

Structural Chemistry of Helicase Inhibition.

Selvaratnam L, Willson TM, Schapira M

J Med Chem. doi: 10.1021/acs.jmedchem.4c01909

Publication date: February 11, 2025

PMID: 39933052

Workflow for E3 Ligase Ligand Validation for PROTAC Development.

Miletić N, Weckesser J, Mosler T, Rathore R, Hoffmann ME, Gehrtz P, Schlesiger S, Hartung IV, Berner N, Wilhelm S, Müller J, Adhikari B, Němec V, Sivashanmugam SA, Elson L, Holzmann H, Schwalm MP, Hoffmann L, Abdul Azeez KR, Müller S, Kuster B, Wolf E, Đikić I, Knapp S

ACS Chem Biol. doi: 10.1021/acschembio.4c00812

Publication date: February 11, 2025

PMID: 39932098