Publications | Structural Genomics Consortium

STAG1 vulnerabilities for exploiting cohesin synthetic lethality in STAG2-deficient cancers.

van der Lelij P, Newman JA, Lieb S, Jude J, Katis V, Hoffmann T, Hinterndorfer M, Bader G, Kraut N, Pearson MA, Peters JM, Zuber J, Gileadi O, Petronczki M

Life Sci Alliance. 3(7):. doi: 10.26508/lsa.202000725

Publication date: May 30, 2020

PMID: 32467316

Bioisosteric Replacement of Arylamide-linked Spine Residues by N-Acylhydrazones and Selenophenes as Design Strategy to Novel Dibenzosuberone Derivatives as Type I½ p38 MAP Kinase Inhibitors.

Galvez Bulh Otilde Es Pedreira JUL, Nahidino P, Kudolo M, Pantsar T, Berger BT, Forster M, Knapp S, Laufer SA, Barreiro EJ

J. Med. Chem.. doi: 10.1021/acs.jmedchem.0c00508

Publication date: May 28, 2020

PMID: 32462866

Defining the Neural Kinome: Strategies and Opportunities for Small Molecule Drug Discovery to Target Neurodegenerative Diseases.

Krahn AI, Wells C, Drewry DH, Beitel LK, Durcan TM, Axtman AD

ACS Chem Neurosci. doi: 10.1021/acschemneuro.0c00176

Publication date: May 28, 2020

PMID: 32464049

HighVia-A Flexible Live-Cell High-Content Screening Pipeline to Assess Cellular Toxicity.

Howarth A, Schröder M, Montenegro RC, Drewry DH, Heba S, Millar V, Müller S, Ebner DV

SLAS Discov. 2472555220923979. doi: 10.1177/2472555220923979

Publication date: May 27, 2020

PMID: 32458721

Structural Basis for the Binding Selectivity of Human CDY Chromodomains.

Dong C, Liu Y, Lyu TJ, Beldar S, Lamb KN, Tempel W, Li Y, Li Z, James LI, Qin S, Wang Y, Min J

Cell Chem Biol. doi: 10.1016/j.chembiol.2020.05.007

Publication date: May 26, 2020

PMID: 32470319

Discovery of highly selective inhibitors of calmodulin-dependent kinases that restore insulin sensitivity in the diet-induced obese in vivo mouse model.

Fromont C, Atzori A, Kaur D, Hashmi L, Greco G, Cabanillas A, Nguyen HV, Jones DH, Garzón M, Varela A, Stevenson B, Iacobini G, Lenoir M, Rajesh S, Box C, Kumar J, Grant P, Novitskaia V, Morgan J, Sorrell F, Redondo C, Kramer A, Harris CJ, Leighton B, Vickers S, Cheetham S, Kenyon C, Grabowska AM, Overduin M, Berditchevski F, Weston CJ, Knapp S, Fischer PM, Butterworth S

J. Med. Chem.. doi: 10.1021/acs.jmedchem.9b01803

Publication date: May 20, 2020

PMID: 32433887

Metabolic Regulation of the Epigenome Drives Lethal Infantile Ependymoma.

Michealraj KA, Kumar SA, Kim LJY, Cavalli FMG, Przelicki D, Wojcik JB, Delaidelli A, Bajic A, Saulnier O, MacLeod G, Vellanki RN, Vladoiu MC, Guilhamon P, Ong W, Lee JJY, Jiang Y, Holgado BL, Rasnitsyn A, Malik AA, Tsai R, Richman CM, Juraschka K, Haapasalo J, Wang EY, De Antonellis P, Suzuki H, Farooq H, Balin P, Kharas K, Van Ommeren R, Sirbu O, Rastan A, Krumholtz SL, Ly M, Ahmadi M, Deblois G, Srikanthan D, Luu B, Loukides J, Wu X, Garzia L, Ramaswamy V, Kanshin E, Sánchez-Osuna M, El-Hamamy I, Coutinho FJ, Prinos P, Singh S, Donovan LK, Daniels C, Schramek D, Tyers M, Weiss S, Stein LD, Lupien M, Wouters BG, Garcia BA, Arrowsmith CH, Sorensen PH, Angers S, Jabado N, Dirks PB, Mack SC, Agnihotri S, Rich JN, Taylor MD

Cell. doi: 10.1016/j.cell.2020.04.047

Publication date: May 20, 2020

PMID: 32445698

Mitochondrial uncoupling protein-dependent signaling in plant bioenergetics and stress response.

Barreto P, Miguez Couñago R, Arruda P

Mitochondrion. doi: 10.1016/j.mito.2020.05.001

Publication date: May 18, 2020

PMID: 32439620

Radiolabeled cCPE Peptides for SPECT Imaging of Claudin-4 Overexpression in Pancreatic Cancer.

Baguña Torres J, Mosley M, Koustoulidou S, Hopkins S, Knapp S, Chaikuad A, Kondoh M, Tachibana K, Kersemans V, Cornelissen B

J. Nucl. Med.. doi: 10.2967/jnumed.120.243113

Publication date: May 15, 2020

PMID: 32414951

Receptor-interacting protein kinase 2 (RIPK2) and nucleotide-binding oligomerization domain (NOD) cell signaling inhibitors based on a 3,5-diphenyl-2-aminopyridine scaffold.

Suebsuwong C, Dai B, Pinkas DM, Duddupudi AL, Li L, Bufton JC, Schlicher L, Gyrd-Hansen M, Hu M, Bullock AN, Degterev A, Cuny GD

Eur J Med Chem. 200:112417. doi: 10.1016/j.ejmech.2020.112417

Publication date: May 15, 2020

PMID: 32505849

Demonstration of the utility of DOS-derived fragment libraries for rapid hit derivatisation in a multidirectional fashion.

Kidd SL, Fowler E, Reinhardt T, Compton T, Mateu N, Newman H, Bellini D, Talon R, McLoughlin J, Krojer T, Aimon A, Bradley A, Fairhead M, Brear P, Díaz-Sáez L, McAuley K, Sore HF, Madin A, O'Donovan DH, Huber KVM, Hyvönen M, von Delft F, Dowson CG, Spring DR

Chem Sci. 11(39):10792-10801. doi: 10.1039/d0sc01232g

Publication date: May 14, 2020

PMID: 34094333

Pharmacological inhibition of PRMT7 links arginine monomethylation to the cellular stress response.

Szewczyk MM, Ishikawa Y, Organ S, Sakai N, Li F, Halabelian L, Ackloo S, Couzens AL, Eram M, Dilworth D, Fukushi H, Harding R, Dela Seña CC, Sugo T, Hayashi K, McLeod D, Zepeda C, Aman A, Sánchez-Osuna M, Bonneil E, Takagi S, Al-Awar R, Tyers M, Richard S, Takizawa M, Gingras AC, Arrowsmith CH, Vedadi M, Brown PJ, Nara H, Barsyte-Lovejoy D

Nat Commun. 11(1):2396. doi: 10.1038/s41467-020-16271-z

Publication date: May 14, 2020

PMID: 32409666

GGPS1 Mutations Cause Muscular Dystrophy/Hearing Loss/Ovarian Insufficiency Syndrome.

Foley AR, Zou Y, Dunford JE, Rooney J, Chandra G, Xiong H, Straub V, Voit T, Romero N, Donkervoort S, Hu Y, Markello T, Horn A, Qebibo L, Dastgir J, Meilleur K, Finkel RS, Fan Y, Mamchaoui K, Duguez S, Nelson I, Laporte J, Santi M, Malfatti E, Maisonobe T, Touraine P, Hirano M, Hughes I, Bushby K, Oppermann U, Böhm J, Jaiswal JK, Stojkovic T, Bönnemann CG

Ann. Neurol.. doi: 10.1002/ana.25772

Publication date: May 13, 2020

PMID: 32403198

Discovery of a First-in-class Protein Arginine Methyltransferase 6 (PRMT6) Covalent Inhibitor.

Shen Y, Li F, Szewczyk MM, Halabelian L, Park KS, Chau I, Dong A, Zeng H, Chen H, Meng F, Barsyte-Lovejoy D, Arrowsmith CH, Brown P, Liu J, Vedadi M, Jin J

J. Med. Chem.. doi: 10.1021/acs.jmedchem.0c00406

Publication date: May 5, 2020

PMID: 32367723

Targeting ALK2: An Open Science Approach to Developing Therapeutics for the Treatment of Diffuse Intrinsic Pontine Glioma.

Ensan D, Smil D, Zepeda-Velázquez CA, Panagopoulos D, Wong JF, Williams EP, Adamson R, Bullock AN, Kiyota T, Aman A, Roberts OG, Edwards AM, O'Meara JA, Isaac MB, Al-Awar R

J. Med. Chem.. doi: 10.1021/acs.jmedchem.0c00395

Publication date: May 5, 2020

PMID: 32369358

Therapeutic targeting of p300/CBP HAT domain for the treatment of NUT midline carcinoma.

Zhang X, Zegar T, Lucas A, Morrison-Smith C, Knox T, French CA, Knapp S, Müller S, Siveke JT

Oncogene. doi: 10.1038/s41388-020-1301-9

Publication date: May 4, 2020

PMID: 32366905

L-thyroxin and the non-classical thyroid hormone TETRAC are potent activators of PPARγ.

Gellrich L, Heitel P, Heering J, Kilu W, Pollinger J, Goebel T, Kahnt A, Arifi S, Pogoda W, Paulke A, Steinhilber D, Proschak E, Wurglics M, Schubert-Zsilavecz M, Chaikuad A, Knapp S, Bischoff I, Fürst R, Merk D

J. Med. Chem.. doi: 10.1021/acs.jmedchem.9b02150

Publication date: May 1, 2020

PMID: 32356658

A lower X-gate in TASK channels traps inhibitors within the vestibule.

Rödström KEJ, Kiper AK, Zhang W, Rinné S, Pike ACW, Goldstein M, Conrad LJ, Delbeck M, Hahn MG, Meier H, Platzk M, Quigley A, Speedman D, Shrestha L, Mukhopadhyay SMM, Burgess-Brown NA, Tucker SJ, Müller T, Decher N, Carpenter EP

Nature. doi: 10.1038/s41586-020-2250-8

Publication date: April 29, 2020

PMID: 32499642

CDK12 inhibition reduces abnormalities in cells from patients with myotonic dystrophy and in a mouse model.

Ketley A, Wojciechowska M, Ghidelli-Disse S, Bamborough P, Ghosh TK, Morato ML, Sedehizadeh S, Malik NA, Tang Z, Powalowska P, Tanner M, Billeter-Clark R, Trueman RC, Geiszler PC, Agostini A, Othman O, Bösche M, Bantscheff M, Rüdiger M, Mossakowska DE, Drewry DH, Zuercher WJ, Thornton CA, Drewes G, Uings I, Hayes CJ, Brook JD

Sci Transl Med. 12(541):. doi: 10.1126/scitranslmed.aaz2415

Publication date: April 29, 2020

PMID: 32350131

Telomere dysfunction cooperates with epigenetic alterations to impair murine embryonic stem cell fate commitment.

Criqui M, Qamra A, Chu TW, Sharma M, Tsao J, Henry DA, Barsyte-Lovejoy D, Arrowsmith CH, Winegarden N, Lupien M, Harrington L

Elife. 9:. doi: 10.7554/eLife.47333

Publication date: April 16, 2020

PMID: 32297856

Crystal structure of DRIK1, a stress-responsive receptor-like pseudokinase, reveals the molecular basis for the absence of ATP binding.

Aquino B, da Silva VCH, Massirer KB, Arruda P

BMC Plant Biol.. 20(1):158. doi: 10.1186/s12870-020-2328-3

Publication date: April 15, 2020

PMID: 32293271

Importance of Quantifying Drug-Target Engagement in Cells.

Stefaniak J, Huber KVM

ACS Med Chem Lett. 11(4):403-406. doi: 10.1021/acsmedchemlett.9b00570

Publication date: April 9, 2020

PMID: 32292539

New Insights into 4-Anilinoquinazolines as Inhibitors of Cardiac Troponin I-Interacting Kinase (TNNi3K).

Asquith CRM, Laitinen T, Wells CI, Tizzard GJ, Zuercher WJ

Molecules. 25(7):. doi: 10.3390/molecules25071697

Publication date: April 7, 2020

PMID: 32272798

The RESOLUTE consortium: unlocking SLC transporters for drug discovery.

Superti-Furga G, Lackner D, Wiedmer T, Ingles-Prieto A, Barbosa B, Girardi E, Goldmann U, Gürtl B, Klavins K, Klimek C, Lindinger S, Liñeiro-Retes E, Müller AC, Onstein S, Redinger G, Reil D, Sedlyarov V, Wolf G, Crawford M, Everley R, Hepworth D, Liu S, Noell S, Piotrowski M, Stanton R, Zhang H, Corallino S, Faedo A, Insidioso M, Maresca G, Redaelli L, Sassone F, Scarabottolo L, Stucchi M, Tarroni P, Tremolada S, Batoulis H, Becker A, Bender E, Chang YN, Ehrmann A, Müller-Fahrnow A, Pütter V, Zindel D, Hamilton B, Lenter M, Santacruz D, Viollet C, Whitehurst C, Johnsson K, Leippe P, Baumgarten B, Chang L, Ibig Y, Pfeifer M, Reinhardt J, Schönbett J, Selzer P, Seuwen K, Bettembourg C, Biton B, Czech J, de Foucauld H, Didier M, Licher T, Mikol V, Pommereau A, Puech F, Yaligara V, Edwards A, Bongers BJ, Heitman LH, IJzerman AP, Sijben HJ, van Westen GJP, Grixti J, Kell DB, Mughal F, Swainston N, Wright-Muelas M, Bohstedt T, Burgess-Brown N, Carpenter L, Dürr K, Hansen J, Scacioc A, Banci G, Colas C, Digles D, Ecker G, Füzi B, Gamsjäger V, Grandits M, Martini R, Troger F, Altermatt P, Doucerain C, Dürrenberger F, Manolova V, Steck AL, Sundström H, Wilhelm M, Steppan CM

Nat Rev Drug Discov. doi: 10.1038/d41573-020-00056-6

Publication date: April 7, 2020

PMID: 32265506

Hotspots API: A Python Package for the Detection of Small Molecule Binding Hotspots and Application to Structure-Based Drug Design.

Curran PR, Radoux C, Smilova MD, Sykes R, Higueruelo A, Bradley A, Marsden BD, Spring DR, Blundell TL, Leach AR, Pitt WR, Cole JC

J Chem Inf Model. doi: 10.1021/acs.jcim.9b00996

Publication date: March 24, 2020

PMID: 32207937

Structural Basis for EPC1-Mediated Recruitment of MBTD1 into the NuA4/TIP60 Acetyltransferase Complex.

Zhang H, Devoucoux M, Song X, Li L, Ayaz G, Cheng H, Tempel W, Dong C, Loppnau P, Côté J, Min J

Cell Rep. 30(12):3996-4002.e4. doi: 10.1016/j.celrep.2020.03.003

Publication date: March 24, 2020

PMID: 32209463

Targeting Cavity-Creating p53 Cancer Mutations with Small-Molecule Stabilizers: the Y220X Paradigm.

Bauer MR, Krämer A, Settanni G, Jones RN, Ni X, Khan Tareque R, Fersht AR, Spencer J, Joerger AC

ACS Chem Biol. 15(3):657-668. doi: 10.1021/acschembio.9b00748

Publication date: March 20, 2020

PMID: 31990523

A Highly Selective Chemical Probe for Activin Receptor-like Kinases ALK4 and ALK5.

Hanke T, Wong JF, Berger BT, Abdi I, Berger LM, Tesch R, Tredup C, Bullock AN, Müller-Knapp S, Knapp S

ACS Chem. Biol.. doi: 10.1021/acschembio.0c00076

Publication date: March 16, 2020

PMID: 32176847

SGC-AAK1-1: A Chemical Probe Targeting AAK1 and BMP2K.

Wells C, Couñago RM, Limas JC, Almeida TL, Cook JG, Drewry DH, Elkins JM, Gileadi O, Kapadia NR, Lorente-Macias A, Pickett JE, Riemen A, Ruela-de-Sousa RR, Willson TM, Zhang C, Zuercher WJ, Zutshi R, Axtman AD

ACS Med Chem Lett. 11(3):340-345. doi: 10.1021/acsmedchemlett.9b00399

Publication date: March 12, 2020

PMID: 32184967

HMCES Functions in the Alternative End-Joining Pathway of the DNA DSB Repair during Class Switch Recombination in B Cells.

Shukla V, Halabelian L, Balagere S, Samaniego-Castruita D, Feldman DE, Arrowsmith CH, Rao A, Aravind L

Mol. Cell. 77(5):1154. doi: 10.1016/j.molcel.2020.02.008

Publication date: March 5, 2020

PMID: 32142687

Histone H3K27me3 demethylases regulate human Th17 cell development and effector functions by impacting on metabolism.

Cribbs AP, Terlecki-Zaniewicz S, Philpott M, Baardman J, Ahern D, Lindow M, Obad S, Oerum H, Sampey B, Mander PK, Penn H, Wordsworth P, Bowness P, de Winther M, Prinjha RK, Feldmann M, Oppermann U

Proc. Natl. Acad. Sci. U.S.A.. doi: 10.1073/pnas.1919893117

Publication date: March 2, 2020

PMID: 32123118

Re-evaluating the mechanism of action of α,β-unsaturated carbonyl DUB inhibitors b-AP15 and VLX1570: a paradigmatic example of unspecific protein crosslinking with Michael acceptor motif-containing drugs.

Ward JA, Pinto-Fernandez A, Cornelissen L, Bonham S, Díaz-Sáez L, Riant O, Huber KVM, Kessler BM, Feron O, Tate EW

J. Med. Chem.. doi: 10.1021/acs.jmedchem.0c00144

Publication date: February 28, 2020

PMID: 32109059

Mutant ACVR1 Arrests Glial Cell Differentiation to Drive Tumorigenesis in Pediatric Gliomas.

Fortin J, Tian R, Zarrabi I, Hill G, Williams E, Sanchez-Duffhues G, Thorikay M, Ramachandran P, Siddaway R, Wong JF, Wu A, Apuzzo LN, Haight J, You-Ten A, Snow BE, Wakeham A, Goldhamer DJ, Schramek D, Bullock AN, Dijke PT, Hawkins C, Mak TW

Cancer Cell. doi: 10.1016/j.ccell.2020.02.002

Publication date: February 21, 2020

PMID: 32142668

Structure-based view of the druggable genome.

Wang J, Yazdani S, Han A, Schapira M

Drug Discov. Today. doi: 10.1016/j.drudis.2020.02.006

Publication date: February 19, 2020

PMID: 32084498

Development of 2-(4-pyridyl)-benzimidazoles as PKN2 chemical tools to probe cancer.

Scott F, Fala AM, Pennicott LE, Reuillon TD, Massirer KB, Elkins JM, Ward SE

Bioorg. Med. Chem. Lett.. 127040. doi: 10.1016/j.bmcl.2020.127040

Publication date: February 17, 2020

PMID: 32085971

Michelanglo: sculpting protein views on web pages without coding.

Ferla MP, Pagnamenta AT, Damerell D, Taylor JC, Marsden BD

Bioinformatics. doi: 10.1093/bioinformatics/btaa104

Publication date: February 15, 2020

PMID: 32061125

Identification of molecular targets for the targeted treatment of gastric cancer using dasatinib.

Montenegro RC, Howarth A, Ceroni A, Fedele V, Farran B, Mesquita FP, Frejno M, Berger BT, Heinzlmeir S, Sailem HZ, Tesch R, Ebner D, Knapp S, Burbano R, Kuster B, Müller S

Oncotarget. 11(5):535-549. doi: 10.18632/oncotarget.27462

Publication date: February 4, 2020

PMID: 32082487

In vitro benchmarking of NF-κB inhibitors.

Harrold AP, Cleary MM, Bharathy N, Lathara M, Berlow NE, Foreman NK, Donson AM, Amani V, Zuercher WJ, Keller C

Eur. J. Pharmacol.. 172981. doi: 10.1016/j.ejphar.2020.172981

Publication date: January 31, 2020

PMID: 32014486

Hepatitis Delta Virus histone mimicry drives the recruitment of chromatin remodelers for viral RNA replication.

Abeywickrama-Samarakoon N, Cortay JC, Sureau C, Müller S, Alfaiate D, Guerrieri F, Chaikuad A, Schröder M, Merle P, Levrero M, Dény P

Nat Commun. 11(1):419. doi: 10.1038/s41467-020-14299-9

Publication date: January 21, 2020

PMID: 31964889

Bi-allelic Variants in TKFC Encoding Triokinase/FMN Cyclase Are Associated with Cataracts and Multisystem Disease.

Wortmann SB, Meunier B, Mestek-Boukhibar L, van den Broek F, Maldonado EM, Clement E, Weghuber D, Spenger J, Jaros Z, Taha F, Yue WW, Heales SJ, Davison JE, Mayr JA, Rahman S

Am. J. Hum. Genet.. doi: 10.1016/j.ajhg.2020.01.005

Publication date: January 17, 2020

PMID: 32004446

In Depth Analysis of Kinase Cross Screening Data to Identify CAMKK2 Inhibitory Scaffolds.

O'Byrne SN, Scott JW, Pilotte JR, Santiago ADS, Langendorf CG, Oakhill JS, Eduful BJ, Couñago RM, Wells CI, Zuercher WJ, Willson TM, Drewry DH

Molecules. 25(2):. doi: 10.3390/molecules25020325

Publication date: January 13, 2020

PMID: 31941153

Overcoming Fungal Echinocandin Resistance through Inhibition of the Non-essential Stress Kinase Yck2.

Caplan T, Lorente-Macías Á, Stogios PJ, Evdokimova E, Hyde S, Wellington MA, Liston S, Iyer KR, Puumala E, Shekhar-Guturja T, Robbins N, Savchenko A, Krysan DJ, Whitesell L, Zuercher WJ, Cowen LE

Cell Chem Biol. doi: 10.1016/j.chembiol.2019.12.008

Publication date: January 6, 2020

PMID: 31924499

Effects of epigenetic pathway inhibitors on corticotroph tumour AtT20 cells.

Lines KE, Filippakopoulos P, Stevenson M, Muller S, Lockstone HE, Wright B, Knapp S, Buck D, Bountra C, Thakker RV

Endocr. Relat. Cancer. doi: 10.1530/ERC-19-0448

Publication date: January 1, 2020

PMID: 31935194

Human MettL3-MettL14 complex is a sequence-specific DNA adenine methyltransferase active on single-strand and unpaired DNA in vitro.

Woodcock CB, Yu D, Hajian T, Li J, Huang Y, Dai N, Corrêa IR, Wu T, Vedadi M, Zhang X, Cheng X

Cell Discov. 5:63. doi: 10.1038/s41421-019-0136-4

Publication date: December 31, 2019

PMID: 31885874

The crystal structure of human forkhead box N1 in complex with DNA reveals the structural basis for forkhead box family specificity.

Newman JA, Aitkenhead H, Gavard AE, Rota IA, Handel AE, Hollander GA, Gileadi O

J. Biol. Chem.. doi: 10.1074/jbc.RA119.010365

Publication date: December 30, 2019

PMID: 31914405

Human MettL3-MettL14 complex is a sequence-specific DNA adenine methyltransferase active on single-strand and unpaired DNA in vitro.

Woodcock CB, Yu D, Hajian T, Li J, Huang Y, Dai N, Corrêa IR, Wu T, Vedadi M, Zhang X, Cheng X

Cell Discov. 5(1):63. doi: 10.1038/s41421-019-0136-4

Publication date: December 24, 2019

PMID: 33353928

Discovery of a chemical probe for PRDM9.

Allali-Hassani A, Szewczyk MM, Ivanochko D, Organ SL, Bok J, Ho JSY, Gay FPH, Li F, Blazer L, Eram MS, Halabelian L, Dilworth D, Luciani GM, Lima-Fernandes E, Wu Q, Loppnau P, Palmer N, Talib SZA, Brown PJ, Schapira M, Kaldis P, O'Hagan RC, Guccione E, Barsyte-Lovejoy D, Arrowsmith CH, Sanders JM, Kattar SD, Bennett DJ, Nicholson B, Vedadi M

Nat Commun. 10(1):5759. doi: 10.1038/s41467-019-13652-x

Publication date: December 17, 2019

PMID: 31848333