Publications | Structural Genomics Consortium

New opportunities for kinase drug repurposing and target discovery.

Knapp S

Br. J. Cancer. doi: 10.1038/s41416-018-0045-6

Publication date: March 16, 2018

PMID: 29545596

Effects of FKBP12 and type II BMP receptors on signal transduction by ALK2 activating mutations associated with genetic disorders.

Machiya A, Tsukamoto S, Ohte S, Kuratani M, Fujimoto M, Kumagai K, Osawa K, Suda N, Bullock AN, Katagiri T

Bone. doi: 10.1016/j.bone.2018.03.015

Publication date: March 15, 2018

PMID: 29551750

Circadian clock component REV-ERBα controls homeostatic regulation of pulmonary inflammation.

Pariollaud M, Gibbs J, Hopwood T, Brown S, Begley N, Vonslow R, Poolman T, Guo B, Saer B, Jones DH, Tellam JP, Bresciani S, Tomkinson NC, Wojno-Picon J, Cooper AW, Daniels DA, Trump RP, Grant D, Zuercher W, Willson TM, MacDonald AS, Bolognese B, Podolin PL, Sanchez Y, Loudon AS, Ray DW

J. Clin. Invest.. doi: 10.1172/JCI93910

Publication date: March 13, 2018

PMID: 29533925

Discovery of a novel allosteric inhibitor scaffold for polyadenosine-diphosphate-ribose polymerase 14 (PARP14) macrodomain 2.

Moustakim M, Riedel K, Schuller M, Gehring AP, Monteiro OP, Martin SP, Fedorov O, Heer J, Dixon DJ, Elkins JM, Knapp S, Bracher F, Brennan PE

Bioorg. Med. Chem.. doi: 10.1016/j.bmc.2018.03.020

Publication date: March 12, 2018

PMID: 29567296

Discovery of Small-Molecule Antagonists of the H3K9me3 Binding to UHRF1 Tandem Tudor Domain.

Senisterra G, Zhu HY, Luo X, Zhang H, Xun G, Lu C, Xiao W, Hajian T, Loppnau P, Chau I, Li F, Allali-Hassani A, Atadja P, Oyang C, Li E, Brown PJ, Arrowsmith CH, Zhao K, Yu Z, Vedadi M

SLAS Discov. 2472555218766278. doi: 10.1177/2472555218766278

Publication date: March 1, 2018

PMID: 29562800

Structural and histone binding studies of the chromo barrel domain of TIP60.

Zhang Y, Lei M, Yang X, Feng Y, Yang Y, Loppnau P, Li Y, Yang Y, Min J, Liu Y

FEBS Lett.. doi: 10.1002/1873-3468.13021

Publication date: March 1, 2018

PMID: 29494751

Creation of a novel class of potent and selective MutT Homolog 1 (MTH1) inhibitors using fragment-based screening and structure-based drug design.

Rahm F, Viklund J, Tresaugues L, Ellermann M, Giese A, Ericsson U, Forsblom R, Ginman T, Günther J, Hallberg K, Lindström J, Persson LB, Silvander C, Talagas A, Díaz-Sáez L, Fedorov O, Huber KVM, Panagakou I, Siejka P, Gorjanacz M, Bauser M, Andersson M

J. Med. Chem.. doi: 10.1021/acs.jmedchem.7b01884

Publication date: February 27, 2018

PMID: 29485874

Oocyte DNA damage quality control requires consecutive interplay of CHK2 and CK1 to activate p63.

Tuppi M, Kehrloesser S, Coutandin DW, Rossi V, Luh LM, Strubel A, Hötte K, Hoffmeister M, Schäfer B, De Oliveira T, Greten F, Stelzer EHK, Knapp S, De Felici M, Behrends C, Klinger FG, Dötsch V

Nat. Struct. Mol. Biol.. doi: 10.1038/s41594-018-0035-7

Publication date: February 26, 2018

PMID: 29483652

Structure activity relationship studies on rhodanines and derived enethiol inhibitors of metallo-β-lactamases.

Zhang D, Markoulides MS, Stepanovs D, Rydzik AM, El-Hussein A, Bon C, Kamps JJAG, Umland KD, Collins PM, Cahill ST, Wang DY, von Delft F, Brem J, McDonough MA, Schofield CJ

Bioorg. Med. Chem.. doi: 10.1016/j.bmc.2018.02.043

Publication date: February 23, 2018

PMID: 29655609

Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry.

Vu H, Pedro L, Mak T, McCormick B, Rowley J, Liu M, Di Capua A, Williams-Noonan B, Pham NB, Pouwer RH, Nguyen B, Andrews KT, Skinner-Adams T, Kim J, Hol WGJ, Hui R, Crowther GJ, Van Voorhis WC, Quinn RJ

ACS Infect Dis. doi: 10.1021/acsinfecdis.7b00197

Publication date: February 13, 2018

PMID: 29436819

Tuning microtubule dynamics to enhance cancer therapy by modulating FER-mediated CRMP2 phosphorylation.

Zheng Y, Sethi R, Mangala LS, Taylor C, Goldsmith J, Wang M, Masuda K, Karaminejadranjbar M, Mannion D, Miranda F, Herrero-Gonzalez S, Hellner K, Chen F, Alsaadi A, Albukhari A, Fotso DC, Yau C, Jiang D, Pradeep S, Rodriguez-Aguayo C, Lopez-Berestein G, Knapp S, Gray NS, Campo L, Myers KA, Dhar S, Ferguson D, Bast RC, Sood AK, von Delft F, Ahmed AA

Nat Commun. 9(1):476. doi: 10.1038/s41467-017-02811-7

Publication date: February 2, 2018

PMID: 29396402

Activation loop targeting strategy for design of receptor-interacting protein kinase 2 (RIPK2) inhibitors.

Suebsuwong C, Pinkas DM, Ray SS, Bufton JC, Dai B, Bullock AN, Degterev A, Cuny GD

Bioorg. Med. Chem. Lett.. doi: 10.1016/j.bmcl.2018.01.044

Publication date: January 31, 2018

PMID: 29409752

An AKAP-Lbc-RhoA interaction inhibitor promotes the translocation of aquaporin-2 to the plasma membrane of renal collecting duct principal cells.

Schrade K, Tröger J, Eldahshan A, Zühlke K, Abdul Azeez KR, Elkins JM, Neuenschwander M, Oder A, Elkewedi M, Jaksch S, Andrae K, Li J, Fernandes J, Müller PM, Grunwald S, Marino SF, Vukićević T, Eichhorst J, Wiesner B, Weber M, Kapiloff M, Rocks O, Daumke O, Wieland T, Knapp S, von Kries JP, Klussmann E

PLoS ONE. 13(1):e0191423. doi: 10.1371/journal.pone.0191423

Publication date: January 27, 2018

PMID: 29373579

CDKL Family Kinases Have Evolved Distinct Structural Features and Ciliary Function.

Canning P, Park K, Gonçalves J, Li C, Howard CJ, Sharpe TD, Holt LJ, Pelletier L, Bullock AN, Leroux MR

Cell Rep. 22(4):885-894. doi: 10.1016/j.celrep.2017.12.083

Publication date: January 23, 2018

PMID: 29420175

Cloning, expression and purification of kinase domains of cacao PR-1 receptor-like kinases.

Tosarini TR, Ramos PZ, de Souza GP, Baroni RM, Massirer KB, Couñago RM, Mondego JMC

Protein Expr. Purif.. doi: 10.1016/j.pep.2018.01.004

Publication date: January 19, 2018

PMID: 29360581

Discovery of Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT).

Babault N, Allali-Hassani A, Li F, Fan J, Yue A, Ju K, Liu F, Vedadi M, Liu J, Jin J

J. Med. Chem.. doi: 10.1021/acs.jmedchem.7b01422

Publication date: January 10, 2018

PMID: 29320176

Revealing the Protein Propionylation Activity of the Histone Acetyltransferase Males absent on the first (MOF).

Han Z, Wu H, Kim S, Yang X, Li Q, Huang H, Cai H, Bartlett MG, Dong A, Zeng H, Brown PJ, Yang X, Arrowsmith CH, Zhao Y, Zheng YG

J. Biol. Chem.. doi: 10.1074/jbc.RA117.000529

Publication date: January 10, 2018

PMID: 29321206

---Inhibition of histone H3K27 demethylase selectively modulates inflammatory phenotypes of natural killer cells.

Cribbs A, Hookway ES, Wells G, Lindow M, Obad S, Oerum H, Prinjha RK, Athanasou N, Sowman A, Philpott M, Penn H, Soderstrom K, Feldmann M, Oppermann U

J. Biol. Chem.. doi: 10.1074/jbc.RA117.000698

Publication date: January 4, 2018

PMID: 29301935

DNA Sequence Recognition of Human CXXC Domains and Their Structural Determinants.

Xu C, Liu K, Lei M, Yang A, Li Y, Hughes TR, Min J

Structure. doi: 10.1016/j.str.2017.11.022

Publication date: December 16, 2017

PMID: 29276034

Discovery of Potent and Selective Allosteric Inhibitors of Protein Arginine Methyltransferase 3 (PRMT3).

Kaniskan HÜ, Eram MS, Zhao K, Szewczyk MM, Yang X, Schmidt K, Luo X, Xiao S, Dai M, He F, Zang I, Lin Y, Li F, Dobrovetsky E, Smil D, Min SJ, Lin-Jones J, Schapira M, Atadja P, Li E, Barsyte-Lovejoy D, Arrowsmith CH, Brown PJ, Liu F, Yu Z, Vedadi M, Jin J

J. Med. Chem.. doi: 10.1021/acs.jmedchem.7b01674

Publication date: December 15, 2017

PMID: 29244490

H3K14ac is linked to methylation of H3K9 by the triple Tudor domain of SETDB1.

Jurkowska RZ, Qin S, Kungulovski G, Tempel W, Liu Y, Bashtrykov P, Stiefelmaier J, Jurkowski TP, Kudithipudi S, Weirich S, Tamas R, Wu H, Dombrovski L, Loppnau P, Reinhardt R, Min J, Jeltsch A

Nat Commun. 8(1):2057. doi: 10.1038/s41467-017-02259-9

Publication date: December 12, 2017

PMID: 29234025

The BEACH-domain containing protein, Nbeal2, interacts with Dock7, Sec16a and Vac14.

Mayer L, Jasztal M, Pardo M, Aguera de Haro S, Collins J, Bariana TK, Smethurst PA, Grassi L, Petersen R, Nurden P, Favier R, Yu L, Meacham S, Astle WJ, Choudhary J, Yue WW, Ouwehand WH, Guerrero JA

Blood. doi: 10.1182/blood-2017-08-800359

Publication date: November 29, 2017

PMID: 29187380

Epigenetic targeting of bromodomain protein BRD4 counteracts cancer cachexia and prolongs survival.

Segatto M, Fittipaldi R, Pin F, Sartori R, Dae Ko K, Zare H, Fenizia C, Zanchettin G, Pierobon ES, Hatakeyama S, Sperti C, Merigliano S, Sandri M, Filippakopoulos P, Costelli P, Sartorelli V, Caretti G

Nat Commun. 8(1):1707. doi: 10.1038/s41467-017-01645-7

Publication date: November 22, 2017

PMID: 29167426

Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers.

Zuliani-Alvarez L, Marzeda AM, Deligne C, Schwenzer A, McCann FE, Marsden BD, Piccinini AM, Midwood KS

Nat Commun. 8(1):1595. doi: 10.1038/s41467-017-01718-7

Publication date: November 17, 2017

PMID: 29150600

Assay interference and off-target liabilities of reported histone acetyltransferase inhibitors.

Dahlin JL, Nelson KM, Strasser JM, Barsyte-Lovejoy D, Szewczyk MM, Organ S, Cuellar M, Singh G, Shrimp JH, Nguyen N, Meier JL, Arrowsmith CH, Brown PJ, Baell JB, Walters MA

Nat Commun. 8(1):1527. doi: 10.1038/s41467-017-01657-3

Publication date: November 15, 2017

PMID: 29142305

Quantitative, Wide-Spectrum Kinase Profiling in Live Cells for Assessing the Effect of Cellular ATP on Target Engagement.

Vasta JD, Corona CR, Wilkinson J, Zimprich CA, Hartnett JR, Ingold MR, Zimmerman K, Machleidt T, Kirkland TA, Huwiler KG, Ohana RF, Slater M, Otto P, Cong M, Wells CI, Berger BT, Hanke T, Glas C, Ding K, Drewry DH, Huber KVM, Willson TM, Knapp S, Müller S, Meisenheimer PL, Fan F, Wood KV, Robers MB

Cell Chem Biol. doi: 10.1016/j.chembiol.2017.10.010

Publication date: November 13, 2017

PMID: 29174542

Structural basis for arginine methylation-independent recognition of PIWIL1 by TDRD2.

Zhang H, Liu K, Izumi N, Huang H, Ding D, Ni Z, Sidhu SS, Chen C, Tomari Y, Min J

Proc. Natl. Acad. Sci. U.S.A.. doi: 10.1073/pnas.1711486114

Publication date: November 8, 2017

PMID: 29118143

The SGC beyond structural genomics: redefining the role of 3D structures by coupling genomic stratification with fragment-based discovery.

Bradley AR, Echalier A, Fairhead M, Strain-Damerell C, Brennan P, Bullock AN, Burgess-Brown NA, Carpenter EP, Gileadi O, Marsden BD, Lee WH, Yue W, Bountra C, von Delft F

Essays Biochem.. 61(5):495-503. doi: 10.1042/EBC20170051

Publication date: November 8, 2017

PMID: 29118096

Exploiting a water network to achieve enthalpy-driven, bromodomain-selective BET inhibitors.

Shadrick WR, Slavish PJ, Chai SC, Waddell B, Connelly M, Low JA, Tallant C, Young BM, Bharatham N, Knapp S, Boyd VA, Morfouace M, Roussel MF, Chen T, Lee RE, Kiplin Guy R, Shelat AA, Potter PM

Bioorg. Med. Chem.. doi: 10.1016/j.bmc.2017.10.042

Publication date: November 4, 2017

PMID: 29170024

Conformational dynamics of the TTD-PHD histone reader module of UHRF1 reveals multiple histone binding states, allosteric regulation and druggability.

Houliston RS, Lemak A, Iqbal A, Ivanochko D, Duan S, Kaustov L, Ong MS, Fan L, Senisterra G, Brown PJ, Wang YX, Arrowsmith CH

J. Biol. Chem.. doi: 10.1074/jbc.M117.799700

Publication date: October 26, 2017

PMID: 29074623

Identification and Optimization of 4-Anilinoquinolines as Inhibitors of Cyclin G Associated Kinase.

Asquith CRM, Laitinen T, Bennett JM, Godoi PH, East MP, Tizzard GJ, Graves LM, Johnson GL, Dornsife RE, Wells CI, Elkins JM, Willson TM, Zuercher W

ChemMedChem. doi: 10.1002/cmdc.201700663

Publication date: October 26, 2017

PMID: 29072804

Characterization of three druggable hotspots in the Aurora-A/TPX2 interaction using biochemical, biophysical and fragment-based approaches.

McIntyre PJ, Collins PM, Vrzal L, Birchall K, Arnold LH, Mpamhanga C, Coombs PJ, Burgess SG, Richards MW, Winter A, Veverka V, von Delft F, Merritt A, Bayliss R

ACS Chem. Biol.. doi: 10.1021/acschembio.7b00537

Publication date: October 18, 2017

PMID: 29045126

Isoform-selective ATAD2 chemical probe with novel chemical structure and unusual mode of action.

Fernández-Montalván AE, Berger M, Kuropka B, Koo SJ, Badock V, Weiske J, Puetter V, Holton SJ, Stöckigt D, Ter Laak A, Centrella PA, Clark MA, Dumelin CE, Sigel EA, Soutter HH, Troast DM, Zhang Y, Cuozzo JW, Keefe AD, Roche D, Rodeschini V, Chaikuad A, Díaz-Sáez L, Bennett JM, Fedorov O, Huber KVM, Huebner J, Weinmann H, Hartung IV, Gorjanacz M

ACS Chem. Biol.. doi: 10.1021/acschembio.7b00708

Publication date: October 18, 2017

PMID: 29043777

WD40 repeat domain proteins: a novel target class?

Schapira M, Tyers M, Torrent M, Arrowsmith CH

Nat Rev Drug Discov. doi: 10.1038/nrd.2017.179

Publication date: October 13, 2017

PMID: 29026209

Small molecule antagonists of the interaction between the histone deacetylase 6 zinc-finger domain and ubiquitin.

Harding RJ, Ferreira de Freitas R, Collins PM, Franzoni I, Ravichandran M, Ouyang H, Juarez-Ornelas KA, Lautens M, Schapira M, von Delft F, Santhakumar V, Arrowsmith CH

J. Med. Chem.. doi: 10.1021/acs.jmedchem.7b00933

Publication date: October 11, 2017

PMID: 29019676

A p53 Super-tumor Suppressor Reveals a Tumor Suppressive p53-Ptpn14-Yap Axis in Pancreatic Cancer.

Mello SS, Valente LJ, Raj N, Seoane JA, Flowers BM, McClendon J, Bieging-Rolett KT, Lee J, Ivanochko D, Kozak MM, Chang DT, Longacre TA, Koong AC, Arrowsmith CH, Kim SK, Vogel H, Wood LD, Hruban RH, Curtis C, Attardi LD

Cancer Cell. 32(4):460-473.e6. doi: 10.1016/j.ccell.2017.09.007

Publication date: October 9, 2017

PMID: 29017057

Discovery of a selective allosteric inhibitor targeting macrodomain 2 of poly-adenosine-diphosphate-ribose polymerases 14.

Schuller M, Riedel K, Gibbs-Seymour I, Uth K, Sieg C, Gehring AP, Ahel I, Bracher F, Kessler BM, Elkins JM, Knapp S

ACS Chem. Biol.. doi: 10.1021/acschembio.7b00445

Publication date: October 9, 2017

PMID: 28991428

Synthesis and Demonstration of the Biological Relevance of sp(3) -rich Scaffolds Distantly Related to Natural Product Frameworks.

Foley DJ, Craven PGE, Collins PM, Doveston RG, Aimon A, Talon R, Churcher I, von Delft F, Marsden SP, Nelson A

Chemistry. doi: 10.1002/chem.201704169

Publication date: October 6, 2017

PMID: 28983993

Synthesis of kinase inhibitors containing a pentafluorosulfanyl moiety.

Sansook S, Ocasio CA, Day IJ, Tizzard GJ, Coles SJ, Fedorov O, Bennett JM, Elkins JM, Spencer J

Org. Biomol. Chem.. doi: 10.1039/c7ob02289a

Publication date: October 6, 2017

PMID: 28984325

Discovery of a highly selective cell-active inhibitor of KDM2/7.

Gerken P, Wolstenhulme J, Tumber A, Hatch S, Zhang Y, Müller S, Chandler S, Mair B, Li F, Nijman S, Konietzny R, Szommer T, Yapp C, Fedorov O, Benesch J, Vedadi M, Kessler B, Kawamura A, Brennan P, Smith MD

Angew. Chem. Int. Ed. Engl.. doi: 10.1002/anie.201706788

Publication date: October 4, 2017

PMID: 28976073

A systematic analysis of atomic protein-ligand interactions in the PDB.

Ferreira de Freitas R, Schapira M

Medchemcomm. 8(10):1970-1981. doi: 10.1039/c7md00381a

Publication date: October 1, 2017

PMID: 29308120

Correction for Bagarova et al., "Constitutively Active ALK2 Receptor Mutants Require Type II Receptor Cooperation".

Bagarova J, Vonner AJ, Armstrong KA, Börgermann J, Lai CSC, Deng DY, Beppu H, Alfano I, Filippakopoulos P, Morrell NW, Bullock AN, Knaus P, Mishina Y, Yu PB

Mol. Cell. Biol.. 37(19):. doi: 10.1128/MCB.00284-17

Publication date: October 1, 2017

PMID: 28899999

Disease Association and Druggability of WD40 Repeat Proteins.

Song R, Wang ZD, Schapira M

J. Proteome Res.. doi: 10.1021/acs.jproteome.7b00451

Publication date: September 28, 2017

PMID: 28956604

Structural Complexity in the KCTD Family of Cullin3-Dependent E3 Ubiquitin Ligases.

Pinkas DM, Sanvitale CE, Bufton JC, Sorrell FJ, Solcan N, Chalk R, Doutch J, Bullock AN

Biochem. J.. doi: 10.1042/BCJ20170527

Publication date: September 28, 2017

PMID: 28963344

Corrigendum: Alternative splicing promotes tumour aggressiveness and drug resistance in African American prostate cancer.

Wang BD, Ceniccola K, Hwang S, Andrawis R, Horvath A, Freedman JA, Olender J, Knapp S, Ching T, Garmire L, Patel V, Garcia-Blanco MA, Patierno SR, Lee NH

Nat Commun. 8:16161. doi: 10.1038/ncomms16161

Publication date: September 27, 2017

PMID: 28952599