Publications | Structural Genomics Consortium

Aminothiazolones as potent, selective and cell active inhibitors of the PIM kinase family.

Quevedo CE, Bataille CJR, Byrne S, Durbin M, Elkins J, Guillermo A, Jones AM, Knapp S, Nadali A, Walker RG, Wilkinson IVL, Wynne GM, Davies SG, Russell AJ

Bioorg Med Chem. 28(22):115724. doi: 10.1016/j.bmc.2020.115724

Publication date: August 26, 2020

PMID: 33128909

Optimization of pyrazolo[1,5-a]pyrimidines lead to the identification of a highly selective casein kinase 2 inhibitor.

Krämer A, Kurz CG, Berger BT, Celik IE, Tjaden A, Greco FA, Knapp S, Hanke T

Eur J Med Chem. 208:112770. doi: 10.1016/j.ejmech.2020.112770

Publication date: August 23, 2020

PMID: 32883634

GLUT1 inhibition blocks growth of RB1-positive triple negative breast cancer.

Wu Q, Ba-Alawi W, Deblois G, Cruickshank J, Duan S, Lima-Fernandes E, Haight J, Tonekaboni SAM, Fortier AM, Kuasne H, McKee TD, Mahmoud H, Kushida M, Cameron S, Dogan-Artun N, Chen W, Nie Y, Zhang LX, Vellanki RN, Zhou S, Prinos P, Wouters BG, Dirks PB, Done SJ, Park M, Cescon DW, Haibe-Kains B, Lupien M, Arrowsmith CH

Nat Commun. 11(1):4205. doi: 10.1038/s41467-020-18020-8

Publication date: August 21, 2020

PMID: 32826891

Selective targeting of the αC and DFG-out pocket in p38 MAPK.

Röhm S, Schröder M, Dwyer JE, Widdowson CS, Chaikuad A, Berger BT, Joerger AC, Krämer A, Harbig J, Dauch D, Kudolo M, Laufer S, Bagley MC, Knapp S

Eur J Med Chem. 208:112721. doi: 10.1016/j.ejmech.2020.112721

Publication date: August 20, 2020

PMID: 33035818

Deliberately Losing Control of C-H Activation Processes in the Design of Small Molecule Fragment Arrays Targeting Peroxisomal Metabolism.

Kahn Tareque R, Hassell-Hart S, Krojer T, Bradley A, Velupillai S, Talon R, Fairhead M, Day IJ, Bala K, Felix R, Kemmitt P, Brennan P, von Delft F, Díaz Sáez L, Spencer J, Huber K

ChemMedChem. doi: 10.1002/cmdc.202000543

Publication date: August 18, 2020

PMID: 32812371

A novel screening approach comparing kinase activity of small molecule inhibitors with similar molecular structures and distinct biologic effects in triple-negative breast cancer to identify targetable signaling pathways.

Matossian MD, Burks HE, Elliott S, Hoang VT, Zuercher WJ, Wells C, Drewry DH, Kapadia N, Chang T, Yan T, Windsor GO, Nguyen K, Fang F, Nephew KP, Buechlein A, Rusch DB, Sabol RA, Ucar DA, Zabaleta J, Miele L, Bunnell BA, Collins-Burow BM, Burow ME

Anticancer Drugs. 31(8):759-775. doi: 10.1097/CAD.0000000000000962

Publication date: August 17, 2020

PMID: 32796402

Potent antiviral activity of novel multi-substituted 4-anilinoquin(az)olines.

Saul S, Pu SY, Zuercher WJ, Einav S, Asquith CRM

Bioorg. Med. Chem. Lett.. 30(16):127284. doi: 10.1016/j.bmcl.2020.127284

Publication date: August 15, 2020

PMID: 32631507

Generation and validation of recombinant antibodies to study human aminoacyl tRNA synthetases.

Preger C, Wigren E, Ossipova E, Marks C, Lengqvist J, Hofström C, Andersson O, Jakobsson PJ, Gräslund S, Persson H

J. Biol. Chem.. doi: 10.1074/jbc.RA120.012893

Publication date: August 14, 2020

PMID: 32817337

Mining Public Domain Data to Develop Selective DYRK1A Inhibitors.

Henderson SH, Sorrell F, Bennett J, Hanley MT, Robinson S, Hopkins Navratilova I, Elkins JM, Ward SE

ACS Med Chem Lett. 11(8):1620-1626. doi: 10.1021/acsmedchemlett.0c00279

Publication date: August 13, 2020

PMID: 32832032

Nucleotide Binding, Evolutionary Insights, and Interaction Partners of the Pseudokinase Unc-51-like Kinase 4.

Preuss F, Chatterjee D, Mathea S, Shrestha S, St-Germain J, Saha M, Kannan N, Raught B, Rottapel R, Knapp S

Structure. doi: 10.1016/j.str.2020.07.016

Publication date: August 13, 2020

PMID: 32814032

DFG-1 residue controls inhibitor binding mode and affinity providing a basis for rational design of kinase inhibitor selectivity.

Schröder M, Bullock AN, Fedorov O, Bracher F, Chaikuad A, Knapp S

J. Med. Chem.. doi: 10.1021/acs.jmedchem.0c00898

Publication date: August 12, 2020

PMID: 32787076

Leveraging an Open Science Drug Discovery Model to Develop CNS Penetrant ALK2 Inhibitors for the Treatment of Diffuse Intrinsic Pontine Glioma.

Smil D, Wong JF, Williams E, Adamson R, Howarth A, McLeod D, Mamai A, Kim S, Wilson B, Kiyota T, Aman A, Owen J, Poda G, Horiuchi K, Kuznetsova E, Ma H, Hamblin JN, Cramp S, Roberts O, Edwards AM, Uehling D, Al-Awar R, Bullock AN, O'Meara J, Isaac M

J. Med. Chem.. doi: 10.1021/acs.jmedchem.0c01199

Publication date: August 11, 2020

PMID: 32787083

Comparative structural analyses and nucleotide-binding characterization of the four KH domains of FUBP1.

Ni X, Knapp S, Chaikuad A

Sci Rep. 10(1):13459. doi: 10.1038/s41598-020-69832-z

Publication date: August 10, 2020

PMID: 32778776

LOTUS domain is a novel class of G-rich and G-quadruplex RNA binding domain.

Ding D, Wei C, Dong K, Liu J, Stanton A, Xu C, Min J, Hu J, Chen C

Nucleic Acids Res.. doi: 10.1093/nar/gkaa652

Publication date: August 7, 2020

PMID: 32766792

Catalytic Domain Plasticity of MKK7 Reveals Structural Mechanisms of Allosteric Activation and Diverse Targeting Opportunities.

Schröder M, Tan L, Wang J, Liang Y, Gray NS, Knapp S, Chaikuad A

Cell Chem Biol. doi: 10.1016/j.chembiol.2020.07.014

Publication date: August 4, 2020

PMID: 32783966

Synergistic drug combinations and machine learning for drug repurposing in chordoma.

Anderson E, Havener TM, Zorn KM, Foil DH, Lane TR, Capuzzi SJ, Morris D, Hickey AJ, Drewry DH, Ekins S

Sci Rep. 10(1):12982. doi: 10.1038/s41598-020-70026-w

Publication date: July 31, 2020

PMID: 32737414

The SNM1A DNA repair nuclease.

Baddock HT, Yosaatmadja Y, Newman JA, Schofield CJ, Gileadi O, McHugh PJ

DNA Repair (Amst.). 95:102941. doi: 10.1016/j.dnarep.2020.102941

Publication date: July 31, 2020

PMID: 32866775

Dataset Augmentation Allows Deep Learning-Based Virtual Screening To Better Generalize To Unseen Target Classes, And Highlight Important Binding Interactions.

Scantlebury J, Brown N, von Delft F, Deane CM

J Chem Inf Model. doi: 10.1021/acs.jcim.0c00263

Publication date: July 23, 2020

PMID: 32701288

Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants.

Neuray C, Maroofian R, Scala M, Sultan T, Pai GS, Mojarrad M, El Khashab H, deHoll L, Yue W, Alsaif HS, Zanetti MN, Bello O, Person R, Eslahi A, Khazaei Z, Feizabadi MH, Efthymiou S, El-Bassyouni HT, Soliman DR, Tekes S, Ozer L, Baltaci V, Khan S, Beetz C, Amr KS, Salpietro V, Jamshidi Y, Alkuraya FS, Houlden H

Brain. doi: 10.1093/brain/awaa178

Publication date: July 23, 2020

PMID: 32705143

Selective Peptidomimetic Inhibitors of NTMT1/2: Rational design, synthesis, characterization, and crystallographic studies.

Mackie BD, Chen D, Dong G, Dong C, Parker H, Tooley C, Noinaj N, Min J, Huang R

J. Med. Chem.. doi: 10.1021/acs.jmedchem.0c00689

Publication date: July 20, 2020

PMID: 32689795

Naturally occurring cobalamin (B12) analogs can function as cofactors for human methylmalonyl-CoA mutase.

Sokolovskaya OM, Plessl T, Bailey H, Mackinnon S, Baumgartner MR, Yue WW, Froese DS, Taga ME

Biochimie. doi: 10.1016/j.biochi.2020.06.014

Publication date: July 10, 2020

PMID: 32659443

The orphan nuclear receptor Nurr1 is responsive to non-steroidal anti-inflammatory drugs.

Willems S, Kilu W, Ni X, Chaikuad A, Knapp S, Heering J, Merk D

Commun Chem. 3(1):85. doi: 10.1038/s42004-020-0331-0

Publication date: July 3, 2020

PMID: 36703399

Alternative splicing and allosteric regulation modulate the chromatin binding of UHRF1.

Tauber M, Kreuz S, Lemak A, Mandal P, Yerkesh Z, Veluchamy A, Al-Gashgari B, Aljahani A, Cortés-Medina LV, Azhibek D, Fan L, Ong MS, Duan S, Houliston S, Arrowsmith CH, Fischle W

Nucleic Acids Res.. doi: 10.1093/nar/gkaa520

Publication date: July 1, 2020

PMID: 32609811

Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism.

Bezerra GA, Foster WR, Bailey HJ, Hicks KG, Sauer SW, Dimitrov B, McCorvie TJ, Okun JG, Rutter J, Kölker S, Yue WW

IUCrJ. 7(Pt 4):693-706. doi: 10.1107/S205225252000696X

Publication date: July 1, 2020

PMID: 32695416

Probing the Plasticity in the Active Site of Protein N-terminal Methyltransferase 1 Using Bisubstrate Analogs.

Chen D, Dong C, Dong G, Srinivasan K, Min J, Noinaj N, Huang R

J. Med. Chem.. doi: 10.1021/acs.jmedchem.0c00770

Publication date: July 1, 2020

PMID: 32605369

Characterization of a dual BET/HDAC inhibitor for treatment of pancreatic ductal adenocarcinoma.

Zhang X, Zegar T, Weiser T, Hamdan FH, Berger BT, Lucas R, Balourdas DI, Ladigan S, Cheung PF, Liffers ST, Trajkovic-Arsic M, Scheffler B, Joerger AC, Hahn SA, Johnsen SA, Knapp S, Siveke JT

Int. J. Cancer. doi: 10.1002/ijc.33137

Publication date: June 29, 2020

PMID: 32599645

Identifying the target of an antiparasitic compound in Toxoplasma using thermal proteome profiling.

Herneisen AL, Sidik SM, Markus BM, Drewry DH, Zuercher WJ, Lourido S

ACS Chem. Biol.. doi: 10.1021/acschembio.0c00369

Publication date: June 29, 2020

PMID: 32597628

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes-7.

Gütschow M, Eynde JJV, Jampilek J, Kang C, Mangoni AA, Fossa P, Karaman R, Trabocchi A, Scott PJH, Reynisson J, Rapposelli S, Galdiero S, Winum JY, Brullo C, Prokai-Tatrai K, Sharma AK, Schapira M, Azuma YT, Cerchia L, Spetea M, Torri G, Collina S, Geronikaki A, García-Sosa AT, Vasconcelos MH, Sousa ME, Kosalec I, Tuccinardi T, Duarte IF, Salvador JAR, Bertinaria M, Pellecchia M, Amato J, Rastelli G, Gomes PAC, Guedes RC, Sabatier JM, Estévez-Braun A, Pagano B, Mangani S, Ragno R, Kokotos G, Brindisi M, González FV, Borges F, Miloso M, Rautio J, Muñoz-Torrero D

Molecules. 25(13):. doi: 10.3390/molecules25132968

Publication date: June 28, 2020

PMID: 32605268

Identification of a PGXPP degron motif in dishevelled and structural basis for its binding to the E3 ligase KLHL12.

Chen Z, Wasney GA, Picaud S, Filippakopoulos P, Vedadi M, D'Angiolella V, Bullock AN

Open Biol. 10(6):200041. doi: 10.1098/rsob.200041

Publication date: June 24, 2020

PMID: 32574548

Structural Insights into Pseudokinase Domains of Receptor Tyrosine Kinases.

Sheetz JB, Mathea S, Karvonen H, Malhotra K, Chatterjee D, Niininen W, Perttilä R, Preuss F, Suresh K, Stayrook SE, Tsutsui Y, Radhakrishnan R, Ungureanu D, Knapp S, Lemmon MA

Mol. Cell. doi: 10.1016/j.molcel.2020.06.018

Publication date: June 24, 2020

PMID: 32619402

Crowdsourcing drug discovery for pandemics.

Chodera J, Lee AA, London N, von Delft F

Nat Chem. doi: 10.1038/s41557-020-0496-2

Publication date: June 18, 2020

PMID: 32555379

Epigenetic switch-induced viral mimicry evasion in chemotherapy resistant breast cancer.

Deblois G, Madani Tonekaboni SA, Grillo G, Martinez C, Kao YI, Tai F, Ettayebi I, Fortier AM, Savage P, Fedor AN, Liu X, Guilhamon P, Lima-Fernandes E, Murison A, Kuasne H, Ba-Alawi W, Cescon DW, Arrowsmith CH, De Carvalho DD, Haibe-Kains B, Locasale JW, Park M, Lupien M

Cancer Discov. doi: 10.1158/2159-8290.CD-19-1493

Publication date: June 16, 2020

PMID: 32546577

Backbone resonance assignments of the catalytic and regulatory domains of Ca2+/calmodulin-dependent protein kinase 1D.

Tong MHG, Jeeves M, Rajesh S, Ludwig C, Lenoir M, Kumar J, McClelland DM, Berditchevski F, Hubbard JA, Kenyon C, Butterworth S, Knapp S, Overduin M

Biomol NMR Assign. doi: 10.1007/s12104-020-09950-x

Publication date: June 13, 2020

PMID: 32535836

Recognition of nonproline N-terminal residues by the Pro/N-degron pathway.

Dong C, Chen SJ, Melnykov A, Weirich S, Sun K, Jeltsch A, Varshavsky A, Min J

Proc. Natl. Acad. Sci. U.S.A.. doi: 10.1073/pnas.2007085117

Publication date: June 8, 2020

PMID: 32513738

Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release.

Bailey HJ, Bezerra GA, Marcero JR, Padhi S, Foster WR, Rembeza E, Roy A, Bishop DF, Desnick RJ, Bulusu G, Dailey HA, Yue WW

Nat Commun. 11(1):2813. doi: 10.1038/s41467-020-16586-x

Publication date: June 4, 2020

PMID: 32499479

Tuning Transcription Factor Availability through Acetylation-Mediated Genomic Redistribution.

Louphrasitthiphol P, Siddaway R, Loffreda A, Pogenberg V, Friedrichsen H, Schepsky A, Zeng Z, Lu M, Strub T, Freter R, Lisle R, Suer E, Thomas B, Schuster-Böckler B, Filippakopoulos P, Middleton M, Lu X, Patton EE, Davidson I, Lambert JP, Wilmanns M, Steingrímsson E, Mazza D, Goding CR

Mol. Cell. doi: 10.1016/j.molcel.2020.05.025

Publication date: June 4, 2020

PMID: 32531202

Quantifying CDK inhibitor selectivity in live cells.

Wells CI, Vasta JD, Corona CR, Wilkinson J, Zimprich CA, Ingold MR, Pickett JE, Drewry DH, Pugh KM, Schwinn MK, Hwang BB, Zegzouti H, Huber KVM, Cong M, Meisenheimer PL, Willson TM, Robers MB

Nat Commun. 11(1):2743. doi: 10.1038/s41467-020-16559-0

Publication date: June 2, 2020

PMID: 32488087

Preclinical drug studies in MEN1-related neuroendocrine neoplasms (MEN1-NENs).

Grozinsky-Glasberg S, Lines KE, Avniel-Polak S, Bountra C, Thakker RV

Endocr. Relat. Cancer. doi: 10.1530/ERC-20-0127

Publication date: June 1, 2020

PMID: 32590358

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