Publications | Structural Genomics Consortium

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

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

Structural Insights into Interaction Mechanisms of Alternative Piperazine-urea YEATS Domain Binders in MLLT1.

Ni X, Heidenreich D, Christott T, Bennett J, Moustakim M, Brennan PE, Fedorov O, Knapp S, Chaikuad A

ACS Med Chem Lett. 10(12):1661-1666. doi: 10.1021/acsmedchemlett.9b00460

Publication date: December 12, 2019

PMID: 31857843

Methyltransferase Inhibitors: Competing with, or Exploiting the Bound Cofactor.

Ferreira de Freitas R, Ivanochko D, Schapira M

Molecules. 24(24):. doi: 10.3390/molecules24244492

Publication date: December 8, 2019

PMID: 31817960

Structural consequences of BMPR2 kinase domain mutations causing pulmonary arterial hypertension.

Chaikuad A, Thangaratnarajah C, von Delft F, Bullock AN

Sci Rep. 9(1):18351. doi: 10.1038/s41598-019-54830-7

Publication date: December 4, 2019

PMID: 31797984

Chemical Probes for Protein Arginine Methyltransferases.

Ming Li AS, Li F, Eram MS, Bolotokova A, Dela Seña CC, Vedadi M

Methods. doi: 10.1016/j.ymeth.2019.11.017

Publication date: December 3, 2019

PMID: 31809836

Synthetic Peptides as Therapeutic Agents: Lessons Learned From Evolutionary Ancient Peptides and Their Transit Across Blood-Brain Barriers.

Lovejoy DA, Hogg DW, Dodsworth TL, Jurado FR, Read CC, D'Aquila AL, Barsyte-Lovejoy D

Front Endocrinol (Lausanne). 10:730. doi: 10.3389/fendo.2019.00730

Publication date: November 30, 2019

PMID: 31781029

Development of Macrocycle Kinase Inhibitors for ALK2 Using Fibrodysplasia Ossificans Progressiva-Derived Endothelial Cells.

Sánchez-Duffhues G, Williams E, Benderitter P, Orlova V, van Wijhe M, Garcia de Vinuesa A, Kerr G, Caradec J, Lodder K, de Boer HC, Goumans MJ, Eekhoff EMW, Morales-Piga A, Bachiller-Corral J, Koolwijk P, Bullock AN, Hoflack J, Ten Dijke P

JBMR Plus. 3(11):e10230. doi: 10.1002/jbm4.10230

Publication date: November 27, 2019

PMID: 31768489

Lipid Interactions of a Ciliary Membrane TRP Channel: Simulation and Structural Studies of Polycystin-2.

Wang Q, Corey RA, Hedger G, Aryal P, Grieben M, Nasrallah C, Baronina A, Pike ACW, Shi J, Carpenter EP, Sansom MSP

Structure. doi: 10.1016/j.str.2019.11.005

Publication date: November 27, 2019

PMID: 31806353

The fungal metabolite chaetocin is a sensitizer for pro-apoptotic therapies in glioblastoma.

Ozyerli-Goknar E, Sur-Erdem I, Seker F, Cingöz A, Kayabolen A, Kahya-Yesil Z, Uyulur F, Gezen M, Tolay N, Erman B, Gönen M, Dunford J, Oppermann U, Bagci-Onder T

Cell Death Dis. 10(12):894. doi: 10.1038/s41419-019-2107-y

Publication date: November 26, 2019

PMID: 31772153

Janus kinase inhibition for autoinflammation in DNASE2 deficiency.

Hong Y, Capitani M, Murphy C, Pandey S, Cavounidis A, Takeshita H, Nanthapisal S, Yasuda T, Bader-Meunier B, McCreary D, Omoyinmi E, Rao A, Booth C, Gilmour K, Sebire N, Shah N, Klein N, Bullock AN, Eleftheriou D, Uhlig HH, Brogan P

J. Allergy Clin. Immunol.. doi: 10.1016/j.jaci.2019.11.020

Publication date: November 24, 2019

PMID: 31775019

An epigenetic screening determines BET proteins as targets to suppress self-renewal and tumorigenicity in canine mammary cancer cells.

Xavier PLP, Cordeiro YG, Alexandre PA, Pires PRL, Saranholi BH, Silva ER, Müller S, Fukumasu H

Sci Rep. 9(1):17363. doi: 10.1038/s41598-019-53915-7

Publication date: November 22, 2019

PMID: 31758045

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. doi: 10.1016/j.molcel.2019.10.031

Publication date: November 15, 2019

PMID: 31806351

Binding and structural analyses of potent inhibitors of the human Ca2+/calmodulin dependent protein kinase kinase 2 (CAMKK2) identified from a collection of commercially-available kinase inhibitors.

Profeta GS, Dos Reis CV, Santiago ADS, Godoi PHC, Fala AM, Wells CI, Sartori R, Salmazo APT, Ramos PZ, Massirer KB, Elkins JM, Drewry DH, Gileadi O, Couñago RM

Sci Rep. 9(1):16452. doi: 10.1038/s41598-019-52795-1

Publication date: November 11, 2019

PMID: 31712618

Emerging tools to investigate bromodomain functions.

Kougnassoukou Tchara PE, Filippakopoulos P, Lambert JP

Methods. doi: 10.1016/j.ymeth.2019.11.003

Publication date: November 11, 2019

PMID: 31726225

A fast iterative synthetic approach towards the identification of novel highly selective p38 MAP kinase inhibitors.

Röhm S, Berger BT, Schröder M, Chaikuad A, Winkel R, Hekking KFW, Benningshof JJC, Mueller G, Tesch R, Kudolo M, Forster M, Laufer SA, Knapp S

J. Med. Chem.. doi: 10.1021/acs.jmedchem.9b01227

Publication date: November 8, 2019

PMID: 31702918

Towards the Development of an In vivo Chemical Probe for Cyclin G Associated Kinase (GAK).

Asquith CRM, Bennett JM, Su L, Laitinen T, Elkins JM, Pickett JE, Wells CI, Li Z, Willson TM, Zuercher WJ

Molecules. 24(22):. doi: 10.3390/molecules24224016

Publication date: November 6, 2019

PMID: 31698822

Multiple direct interactions of TBP with the MYC oncoprotein.

Wei Y, Resetca D, Li Z, Johansson-Åkhe I, Ahlner A, Helander S, Wallenhammar A, Morad V, Raught B, Wallner B, Kokubo T, Tong Y, Penn LZ, Sunnerhagen M

Nat. Struct. Mol. Biol.. doi: 10.1038/s41594-019-0321-z

Publication date: November 4, 2019

PMID: 31686052