Publications | Structural Genomics Consortium

SGC-CAMKK2-1: A Chemical Probe for CAMKK2.

Wells C, Liang Y, Pulliam TL, Lin C, Awad D, Eduful B, O'Byrne S, Hossain MA, Catta-Preta CMC, Ramos PZ, Gileadi O, Gileadi C, Couñago RM, Stork B, Langendorf CG, Nay K, Oakhill JS, Mukherjee D, Racioppi L, Means AR, York B, McDonnell DP, Scott JW, Frigo DE, Drewry DH

Cells. 12(2):. doi: 10.3390/cells12020287

Publication date: January 11, 2023

PMID: 36672221

Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 macrodomain of SARS-CoV-2.

Gahbauer S, Correy GJ, Schuller M, Ferla MP, Doruk YU, Rachman M, Wu T, Diolaiti M, Wang S, Neitz RJ, Fearon D, Radchenko DS, Moroz YS, Irwin JJ, Renslo AR, Taylor JC, Gestwicki JE, von Delft F, Ashworth A, Ahel I, Shoichet BK, Fraser JS

Proc Natl Acad Sci U S A. 120(2):e2212931120. doi: 10.1073/pnas.2212931120

Publication date: January 10, 2023

PMID: 36598939

Discovery of potent Plasmodium falciparum protein kinase 6 (PfPK6) inhibitors with a type II inhibitor pharmacophore.

Ong HW, Truong A, Kwarcinski F, de Silva C, Avalani K, Havener TM, Chirgwin M, Galal KA, Willis C, Krämer A, Liu S, Knapp S, Derbyshire ER, Zutshi R, Drewry DH

Eur J Med Chem. 249:115043. doi: 10.1016/j.ejmech.2022.115043

Publication date: December 30, 2022

PMID: 36736152

Development of a Potent Cyclic Peptide Inhibitor of the nNOS/PSD-95 Interaction.

Balboa JR, Essig DJ, Ma S, Karer N, Clemmensen LS, Pedersen SW, Joerger AC, Knapp S, Østergaard S, Strømgaard K

J Med Chem. doi: 10.1021/acs.jmedchem.2c01803

Publication date: December 29, 2022

PMID: 36580549

Systematic Design of Adenosine Analogs as Inhibitors of a Clostridioides difficile-Specific DNA Adenine Methyltransferase Required for Normal Sporulation and Persistence.

Zhou J, Horton JR, Menna M, Fiorentino F, Ren R, Yu D, Hajian T, Vedadi M, Mazzoccanti G, Ciogli A, Weinhold E, Hüben M, Blumenthal RM, Zhang X, Mai A, Rotili D, Cheng X

J Med Chem. doi: 10.1021/acs.jmedchem.2c01789

Publication date: December 29, 2022

PMID: 36581322

Skeletal muscle metabolism and contraction performance regulation by teneurin C-terminal-associated peptide-1.

Hogg DW, Reid AL, Dodsworth TL, Chen Y, Reid RM, Xu M, Husic M, Biga PR, Slee A, Buck LT, Barsyte-Lovejoy D, Locke M, Lovejoy DA

Front Physiol. 13:1031264. doi: 10.3389/fphys.2022.1031264

Publication date: December 17, 2022

PMID: 36523555

High-content live-cell multiplex screen for chemogenomic compound annotation based on nuclear morphology.

Tjaden A, Giessmann RT, Knapp S, Schröder M, Müller S

STAR Protoc. 3(4):101791. doi: 10.1016/j.xpro.2022.101791

Publication date: December 16, 2022

PMID: 36317177

MSC-1186, a Highly Selective Pan-SRPK Inhibitor Based on an Exceptionally Decorated Benzimidazole-Pyrimidine Core.

Schröder M, Leiendecker M, Grädler U, Braun J, Blum A, Wanior M, Berger BT, Krämer A, Müller S, Esdar C, Knapp S, Heinrich T

J Med Chem. doi: 10.1021/acs.jmedchem.2c01705

Publication date: December 14, 2022

PMID: 36516476

The future of chemical probes is diversity.

Müller S, Frye S, Baell J

RSC Med Chem. 13(12):1438. doi: 10.1039/d2md90036j

Publication date: December 14, 2022

PMID: 36561071

Identification of highly specific antibodies for Serine/threonine-protein kinase TBK1 for use in immunoblot, immunoprecipitation and immunofluorescence.

Alshafie W, Fotouhi M, Shlaifer I, Ayoubi R, Edwards AM, Durcan TM, McPherson PS, Laflamme C

F1000Res. 11:977. doi: 10.12688/f1000research.124632.2

Publication date: December 7, 2022

PMID: 36415206

Distal extracellular teneurin region (teneurin C-terminal associated peptide; TCAP) possesses independent intracellular calcium regulating actions, in vitro: A potential antagonist of corticotropin-releasing factor (CRF).

Hogg DW, Casatti CC, Belsham DD, Baršytė-Lovejoy D, Lovejoy DA

Biochem Biophys Rep. 32:101397. doi: 10.1016/j.bbrep.2022.101397

Publication date: December 6, 2022

PMID: 36467544

Autoantigenic properties of the aminoacyl tRNA synthetase family in idiopathic inflammatory myopathies.

Preger C, Notarnicola A, Hellström C, Wigren E, Fernandes-Cerqueira C, Kvarnström M, Wahren-Herlenius M, Idborg H, Lundberg IE, Persson H, Gräslund S, Jakobsson PJ

J Autoimmun. 134:102951. doi: 10.1016/j.jaut.2022.102951

Publication date: December 2, 2022

PMID: 36470210

An open source plant kinase chemogenomics set.

Ercoli MF, Ramos PZ, Jain R, Pilotte J, Dong OX, Thompson T, Wells CI, Elkins JM, Edwards AM, Couñago RM, Drewry DH, Ronald PC

Plant Direct. 6(11):e460. doi: 10.1002/pld3.460

Publication date: December 1, 2022

PMID: 36447653

Discovery of 3-Amino-1H-pyrazole-Based Kinase Inhibitors to Illuminate the Understudied PCTAIRE Family.

Amrhein JA, Berger LM, Tjaden A, Krämer A, Elson L, Tolvanen T, Martinez-Molina D, Kaiser A, Schubert-Zsilavecz M, Müller S, Knapp S, Hanke T

Int J Mol Sci. 23(23):. doi: 10.3390/ijms232314834

Publication date: November 27, 2022

PMID: 36499165

ProxyBind: A compendium of binding sites for proximity-induced pharmacology.

Rovers E, Liu L, Schapira M

Comput Struct Biotechnol J. 20:6163-6171. doi: 10.1016/j.csbj.2022.11.010

Publication date: November 25, 2022

PMID: 36420167

Macrocyclization of Quinazoline-Based EGFR Inhibitors Leads to Exclusive Mutant Selectivity for EGFR L858R and Del19.

Amrhein JA, Beyett TS, Feng WW, Krämer A, Weckesser J, Schaeffner IK, Rana JK, Jänne PA, Eck MJ, Knapp S, Hanke T

J Med Chem. doi: 10.1021/acs.jmedchem.2c01041

Publication date: November 16, 2022

PMID: 36384036

Discovery of Nanomolar-Affinity Pharmacological Chaperones Stabilizing the Oncogenic p53 Mutant Y220C.

Stephenson Clarke JR, Douglas LR, Duriez PJ, Balourdas DI, Joerger AC, Khadiullina R, Bulatov E, Baud MGJ

ACS Pharmacol Transl Sci. 5(11):1169-1180. doi: 10.1021/acsptsci.2c00164

Publication date: November 11, 2022

PMID: 36407959

Comparative structural analyses of the NHL domains from the human E3 ligase TRIM-NHL family.

Chaikuad A, Zhubi R, Tredup C, Knapp S

IUCrJ. 9(Pt 6):720-727. doi: 10.1107/S2052252522008582

Publication date: November 1, 2022

PMID: 36381143

Phosphorylation of the DNA repair scaffold SLX4 drives folding of the SAP domain and activation of the MUS81-EME1 endonuclease.

Payliss BJ, Tse YWE, Reichheld SE, Lemak A, Yun HY, Houliston S, Patel A, Arrowsmith CH, Sharpe S, Wyatt HDM

Cell Rep. 41(4):111537. doi: 10.1016/j.celrep.2022.111537

Publication date: October 25, 2022

PMID: 36288699

The Chemical Probes Portal: an expert review-based public resource to empower chemical probe assessment, selection and use.

Antolin AA, Sanfelice D, Crisp A, Villasclaras Fernandez E, Mica IL, Chen Y, Collins I, Edwards A, Müller S, Al-Lazikani B, Workman P

Nucleic Acids Res. doi: 10.1093/nar/gkac909

Publication date: October 21, 2022

PMID: 36268860

Discovery of Hit Compounds for Methyl-lysine Reader Proteins from a Target Class DNA-Encoded Library.

Shell DJ, Rectenwald JM, Buttery PH, Johnson RL, Foley CA, Guduru SKR, Uguen M, Rubiano JS, Zhang X, Li F, Norris-Drouin JL, Axtman M, Brian Hardy P, Vedadi M, Frye SV, James LI, Pearce KH

SLAS Discov. doi: 10.1016/j.slasd.2022.10.003

Publication date: October 19, 2022

PMID: 36272689

Generative and reinforcement learning approaches for the automated de novo design of bioactive compounds.

Korshunova M, Huang N, Capuzzi S, Radchenko DS, Savych O, Moroz YS, Wells CI, Willson TM, Tropsha A, Isayev O

Commun Chem. 5(1):129. doi: 10.1038/s42004-022-00733-0

Publication date: October 18, 2022

PMID: 36697952

PBRM1, SETD2 and BAP1 - the trinity of 3p in clear cell renal cell carcinoma.

Walton J, Lawson K, Prinos P, Finelli A, Arrowsmith C, Ailles L

Nat Rev Urol. doi: 10.1038/s41585-022-00659-1

Publication date: October 17, 2022

PMID: 36253570

Dissecting the stability determinants of a challenging de novo protein fold using massively parallel design and experimentation.

Kim TE, Tsuboyama K, Houliston S, Martell CM, Phoumyvong CM, Lemak A, Haddox HK, Arrowsmith CH, Rocklin GJ

Proc Natl Acad Sci U S A. 119(41):e2122676119. doi: 10.1073/pnas.2122676119

Publication date: October 11, 2022

PMID: 36191185

A Screening of Epigenetic Therapeutic Targets for Non-Small Cell Lung Cancer Reveals PADI4 and KDM6B as Promising Candidates.

Lesbon JCC, Garnica TK, Xavier PLP, Rochetti AL, Reis RM, Müller S, Fukumasu H

Int J Mol Sci. 23(19):. doi: 10.3390/ijms231911911

Publication date: October 7, 2022

PMID: 36233212

De novo design of immunoglobulin-like domains.

Chidyausiku TM, Mendes SR, Klima JC, Nadal M, Eckhard U, Roel-Touris J, Houliston S, Guevara T, Haddox HK, Moyer A, Arrowsmith CH, Gomis-Rüth FX, Baker D, Marcos E

Nat Commun. 13(1):5661. doi: 10.1038/s41467-022-33004-6

Publication date: October 3, 2022

PMID: 36192397

Covalent Modification of Bromodomain Proteins by Peptides Containing a DNA Damage-Induced, Histone Post-Translational Modification.

Jacinto MP, Heidenreich D, Müller S, Greenberg MM

Chembiochem. e202200373. doi: 10.1002/cbic.202200373

Publication date: September 29, 2022

PMID: 36173930

ChemBioPort: an online portal to navigate the structure, function and chemical inhibition of the human proteome.

Liu L, Rovers E, Schapira M

Database (Oxford). 2022:. doi: 10.1093/database/baac088

Publication date: September 27, 2022

PMID: 36164975

Identification of Novel 2,4,5-Trisubstituted Pyrimidines as Potent Dual Inhibitors of Plasmodial PfGSK3/PfPK6 with Activity against Blood Stage Parasites In Vitro.

Galal KA, Truong A, Kwarcinski F, de Silva C, Avalani K, Havener TM, Chirgwin ME, Merten E, Ong HW, Willis C, Abdelwaly A, Helal MA, Derbyshire ER, Zutshi R, Drewry DH

J Med Chem. doi: 10.1021/acs.jmedchem.2c00996

Publication date: September 27, 2022

PMID: 36166733

Development and Characterization of Type I, Type II, and Type III LIM-Kinase Chemical Probes.

Hanke T, Mathea S, Woortman J, Salah E, Berger BT, Tumber A, Kashima R, Hata A, Kuster B, Müller S, Knapp S

J Med Chem. doi: 10.1021/acs.jmedchem.2c01106

Publication date: September 22, 2022

PMID: 36136092

Fragment-based discovery of orphan nuclear receptor Nur77/NGFI-B ligands.

Arifi S, Zaienne D, Heering J, Wein T, Zhubi R, Chaikuad A, Knapp S, Marschner JA, Merk D

Bioorg Chem. 129:106164. doi: 10.1016/j.bioorg.2022.106164

Publication date: September 17, 2022

PMID: 36162288

A small molecule antagonist of SMN disrupts the interaction between SMN and RNAP II.

Liu Y, Iqbal A, Li W, Ni Z, Wang Y, Ramprasad J, Abraham KJ, Zhang M, Zhao DY, Qin S, Loppnau P, Jiang H, Guo X, Brown PJ, Zhen X, Xu G, Mekhail K, Ji X, Bedford MT, Greenblatt JF, Min J

Nat Commun. 13(1):5453. doi: 10.1038/s41467-022-33229-5

Publication date: September 16, 2022

PMID: 36114190

Identification and Utilization of a Chemical Probe to Interrogate the Roles of PIKfyve in the Lifecycle of β-Coronaviruses.

Drewry DH, Potjewyd FM, Bayati A, Smith JL, Dickmander RJ, Howell S, Taft-Benz S, Min SM, Hossain MA, Heise M, McPherson PS, Moorman NJ, Axtman AD

J Med Chem. doi: 10.1021/acs.jmedchem.2c00697

Publication date: September 16, 2022

PMID: 36111834

CDK11 regulates pre-mRNA splicing by phosphorylation of SF3B1.

Hluchý M, Gajdušková P, Ruiz de Los Mozos I, Rájecký M, Kluge M, Berger BT, Slabá Z, Potěšil D, Weiß E, Ule J, Zdráhal Z, Knapp S, Paruch K, Friedel CC, Blazek D

Nature. doi: 10.1038/s41586-022-05204-z

Publication date: September 14, 2022

PMID: 36104565

Identification of Histone Peptide Binding Specificity and Small-Molecule Ligands for the TRIM33α and TRIM33β Bromodomains.

Sekirnik AR, Reynolds JK, See L, Bluck JP, Scorah AR, Tallant C, Lee B, Leszczynska KB, Grimley RL, Storer RI, Malattia M, Crespillo S, Caria S, Duclos S, Hammond EM, Knapp S, Morris GM, Duarte F, Biggin PC, Conway SJ

ACS Chem Biol. doi: 10.1021/acschembio.2c00266

Publication date: September 13, 2022

PMID: 36098557

Combinatorial Anticancer Drug Screen Identifies Off-Target Effects of Epigenetic Chemical Probes.

Barghout SH, Mann MK, Aman A, Yu Y, Alteen MG, Schimmer AD, Schapira M, Arrowsmith CH, Barsyte-Lovejoy D

ACS Chem Biol. doi: 10.1021/acschembio.2c00451

Publication date: September 9, 2022

PMID: 36084291

Structural basis for Gemin5 decamer-mediated mRNA binding.

Guo Q, Zhao S, Francisco-Velilla R, Zhang J, Embarc-Buh A, Abellan S, Lv M, Tang P, Gong Q, Shen H, Sun L, Yao X, Min J, Shi Y, Martínez-Salas E, Zhang K, Xu C

Nat Commun. 13(1):5166. doi: 10.1038/s41467-022-32883-z

Publication date: September 2, 2022

PMID: 36056043

Crystal structure of SARS-CoV-2 nsp10-nsp16 in complex with small molecule inhibitors, SS148 and WZ16.

Klima M, Khalili Yazdi A, Li F, Chau I, Hajian T, Bolotokova A, Kaniskan HÜ, Han Y, Wang K, Li D, Luo M, Jin J, Boura E, Vedadi M

Protein Sci. 31(9):e4395. doi: 10.1002/pro.4395

Publication date: August 31, 2022

PMID: 36040262

PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain.

Malik AU, Karapetsas A, Nirujogi RS, Chatterjee D, Phung TK, Wightman M, Gourlay R, Morrice NA, Mathea S, Knapp S, Alessi DR

Biochem J. doi: 10.1042/BCJ20220308

Publication date: August 30, 2022

PMID: 36040231

PROTAC degraders as chemical probes for studying target biology and target validation.

Němec V, Schwalm MP, Müller S, Knapp S

Chem Soc Rev. doi: 10.1039/d2cs00478j

Publication date: August 25, 2022

PMID: 36004812

Pharmacokinetic Optimization of Small Molecule Janus Kinase 3 Inhibitors to Target Immune Cells.

Laux J, Forster M, Riexinger L, Schwamborn A, Guezguez J, Pokoj C, Kudolo M, Berger LM, Knapp S, Schollmeyer D, Guse J, Burnet M, Laufer SA

ACS Pharmacol Transl Sci. 5(8):573-602. doi: 10.1021/acsptsci.2c00054

Publication date: August 12, 2022

PMID: 35983274

Discovery of novel druggable pockets on polyomavirus VP1 through crystallographic fragment-based screening to develop capsid assembly inhibitors.

Osipov EM, Munawar AH, Beelen S, Fearon D, Douangamath A, Wild C, Weeks SD, Van Aerschot A, von Delft F, Strelkov SV

RSC Chem Biol. 3(8):1013-1027. doi: 10.1039/d2cb00052k

Publication date: August 3, 2022

PMID: 35974998

Compilation and evaluation of a fatty acid mimetics screening library.

Ehrler JHM, Brunst S, Tjaden A, Kilu W, Heering J, Hernandez-Olmos V, Krommes A, Kramer JS, Steinhilber D, Schubert-Zsilavecz M, Müller S, Merk D, Proschak E

Biochem Pharmacol. 204:115191. doi: 10.1016/j.bcp.2022.115191

Publication date: July 27, 2022

PMID: 35907497

Enzymatic nucleosome acetylation selectively affects activity of histone methyltransferases in vitro.

Trush VV, Feller C, Li ASM, Allali-Hassani A, Szewczyk MM, Chau I, Eram MS, Jiang B, Luu R, Zhang F, Barsyte-Lovejoy D, Aebersold R, Arrowsmith CH, Vedadi M

Biochim Biophys Acta Gene Regul Mech. 194845. doi: 10.1016/j.bbagrm.2022.194845

Publication date: July 27, 2022

PMID: 35907431

Cryo-EM structure of the human Kv3.1 channel reveals gating control by the cytoplasmic T1 domain.

Chi G, Liang Q, Sridhar A, Cowgill JB, Sader K, Radjainia M, Qian P, Castro-Hartmann P, Venkaya S, Singh NK, McKinley G, Fernandez-Cid A, Mukhopadhyay SMM, Burgess-Brown NA, Delemotte L, Covarrubias M, Dürr KL

Nat Commun. 13(1):4087. doi: 10.1038/s41467-022-29594-w

Publication date: July 15, 2022

PMID: 35840580

A New Chemotype of Chemically Tractable Nonsteroidal Estrogens Based on a Thieno[2,3-d]pyrimidine Core.

Sammeta VR, Norris JD, Artham S, Torrice CD, Byemerwa J, Joiner C, Fanning SW, McDonnell DP, Willson TM

ACS Med Chem Lett. 13(7):1151-1158. doi: 10.1021/acsmedchemlett.2c00180

Publication date: July 14, 2022

PMID: 35859859

Kinetic Characterization of SARS-CoV-2 nsp13 ATPase Activity and Discovery of Small-Molecule Inhibitors.

Yazdi AK, Pakarian P, Perveen S, Hajian T, Santhakumar V, Bolotokova A, Li F, Vedadi M

ACS Infect Dis. doi: 10.1021/acsinfecdis.2c00165

Publication date: July 13, 2022

PMID: 35822715

Binding adaptation of GS-441524 diversifies macro domains and downregulate SARS-CoV-2 de-MARylation capacity.

Tsika AC, Gallo A, Fourkiotis NK, Argyriou AI, Sreeramulu S, Löhr F, Rogov VV, Richter C, Linhard V, Gande SL, Altincekic N, Krishnathas R, Elamri I, Schwalbe H, Wollenhaupt J, Weiss MS, Spyroulias GA

J Mol Biol. 167720. doi: 10.1016/j.jmb.2022.167720

Publication date: July 12, 2022

PMID: 35839840

A Target Engagement Assay to Assess Uptake, Potency, and Retention of Antibiotics in Living Bacteria.

Fanti RC, Vasconcelos SNS, Catta-Preta CMC, Sullivan JR, Riboldi GP, Dos Reis CV, Ramos PZ, Edwards AM, Behr MA, Couñago RM

ACS Infect Dis. doi: 10.1021/acsinfecdis.2c00073

Publication date: July 11, 2022

PMID: 35815896

CACHE (Critical Assessment of Computational Hit-finding Experiments): A public-private partnership benchmarking initiative to enable the development of computational methods for hit-finding.

Ackloo S, Al-Awar R, Amaro RE, Arrowsmith CH, Azevedo H, Batey RA, Bengio Y, Betz UAK, Bologa CG, Chodera JD, Cornell WD, Dunham I, Ecker GF, Edfeldt K, Edwards AM, Gilson MK, Gordijo CR, Hessler G, Hillisch A, Hogner A, Irwin JJ, Jansen JM, Kuhn D, Leach AR, Lee AA, Lessel U, Morgan MR, Moult J, Muegge I, Oprea TI, Perry BG, Riley P, Rousseaux SAL, Saikatendu KS, Santhakumar V, Schapira M, Scholten C, Todd MH, Vedadi M, Volkamer A, Willson TM

Nat Rev Chem. 6(4):287-295. doi: 10.1038/s41570-022-00363-z

Publication date: July 6, 2022

PMID: 35783295