Apirat Chaikuad

Principal Investigator

Frankfurt
chaikuad@pharmchem.uni-frankfurt.de
+49 (0)69 798-29401

Apirat Chaikuad is a senior scientist at Frankfurt University. He studied biology at Chulalongkorn University (Thailand) and later did a PhD in structural biology at University of Bristol (UK). He joined the Structural Genomics Consortium at the University of Oxford in 2008 to work with Frank von Delft in the crystallography team. During this time, he successfully developed the newly-minimized BCS crystallization screen by incorporating a novel defined PEG smears method, which is now commercially available.

He was also awarded the Emanoel Lee Junior Research Fellowship from St Cross College and a merit award from University of Oxford. Later, he has joined the team of Prof. Stefan Knapp. His current research interests focus primarily on structural biology and chemical biology of signaling pathway, essentially protein kinases.

Structures of PGAM5 Provide Insight into Active Site Plasticity and Multimeric Assembly.
Chaikuad A, Filippakopoulos P, Marcsisin SR, Picaud S, Schröder M, Sekine S, Ichijo H, Engen JR, Takeda K, Knapp S
Structure. 2017 . doi: 10.1016/j.str.2017.05.020
PMID: 28648608

Structural Basis of Intracellular TGF-β Signaling: Receptors and Smads.
Chaikuad A, Bullock AN
Cold Spring Harb Perspect Biol. 2016 . doi: 10.1101/cshperspect.a022111
PMID: 27549117

Structure-based identification of inhibitory fragments targeting the p300/CBP-associated factor bromodomain.
Chaikuad A, Lang S, Brennan PE, Temperini C, Fedorov O, Hollander J, Nachane R, Abell C, Müller S, Siegal G, Knapp S
J. Med. Chem.. 2016 . doi: 10.1021/acs.jmedchem.5b01719
PMID: 26731131

A unique inhibitor binding site in ERK1/2 is associated with slow binding kinetics.
Chaikuad A, M C Tacconi E, Zimmer J, Liang Y, Gray NS, Tarsounas M, Knapp S
Nat. Chem. Biol.. 2014 . doi: 10.1038/nchembio.1629
PMID: 25195011

2021

Structure-Based Design of Dual Partial Peroxisome Proliferator-Activated Receptor γ Agonists/Soluble Epoxide Hydrolase Inhibitors.
Lillich FF, Willems S, Ni X, Kilu W, Borkowsky C, Brodsky M, Kramer JS, Brunst S, Hernandez-Olmos V, Heering J, Schierle S, Kestner RI, Mayser FM, Helmstädter M, Göbel T, Weizel L, Namgaladze D, Kaiser A, Steinhilber D, Pfeilschifter W, Kahnt AS, Proschak A, Chaikuad A, Knapp S, Merk D, Proschak E
J Med Chem. 24.11.2021 . doi: 10.1021/acs.jmedchem.1c01331
PMID: 34818007

Inhibitors of the Hippo Pathway Kinases STK3/MST2 and STK4/MST1 Have Utility for the Treatment of Acute Myeloid Leukemia.
Bata N, Chaikuad A, Bakas NA, Limpert AS, Lambert LJ, Sheffler DJ, Berger LM, Liu G, Yuan C, Wang L, Peng Y, Dong J, Celeridad M, Layng F, Knapp S, Cosford NDP
J Med Chem. 22.11.2021 . doi: 10.1021/acs.jmedchem.1c00804
PMID: 34807584

Discovery of a Potent and Highly Isoform-Selective Inhibitor of the Neglected Ribosomal Protein S6 Kinase Beta 2 (S6K2).
Gerstenecker S, Haarer L, Schröder M, Kudolo M, Schwalm MP, Wydra V, Serafim RAM, Chaikuad A, Knapp S, Laufer S, Gehringer M
Cancers (Basel). 13.10.2021 13(20):. doi: 10.3390/cancers13205133
PMID: 34680283

Design and Development of a Chemical Probe for Pseudokinase Ca2+/calmodulin-Dependent Ser/Thr Kinase.
Russ N, Schröder M, Berger BT, Mandel S, Aydogan Y, Mauer S, Pohl C, Drewry DH, Chaikuad A, Müller S, Knapp S
J Med Chem. 20.9.2021 . doi: 10.1021/acs.jmedchem.1c00845
PMID: 34543009

Assessing reversible and irreversible binding effects of kinase covalent inhibitors through ADP-Glo assays.
Schröder M, Chaikuad A
STAR Protoc. 17.9.2021 2(3):100717. doi: 10.1016/j.xpro.2021.100717
PMID: 34401783

Crystal Structure-Guided Design of Bisubstrate Inhibitors and Photoluminescent Probes for Protein Kinases of the PIM Family.
Nonga OE, Lavogina D, Enkvist E, Kestav K, Chaikuad A, Dixon-Clarke SE, Bullock AN, Kopanchuk S, Ivan T, Ekambaram R, Viht K, Knapp S, Uri A
Molecules. 19.7.2021 26(14):. doi: 10.3390/molecules26144353
PMID: 34299628

Propranolol Activates the Orphan Nuclear Receptor TLX to Counteract Proliferation and Migration of Glioblastoma Cells.
Faudone G, Bischoff-Kont I, Rachor L, Willems S, Zhubi R, Kaiser A, Chaikuad A, Knapp S, Fürst R, Heering J, Merk D
J Med Chem. 11.6.2021 . doi: 10.1021/acs.jmedchem.1c00733
PMID: 34115934

Controlling the Covalent Reactivity of a Kinase Inhibitor with Light.
Reynders M, Chaikuad A, Berger BT, Bauer K, Koch P, Laufer S, Knapp S, Trauner D
Angew Chem Int Ed Engl. 3.6.2021 . doi: 10.1002/anie.202103767
PMID: 34081840

Large-Scale Recombinant Production of the SARS-CoV-2 Proteome for High-Throughput and Structural Biology Applications.
Altincekic N, Korn SM, Qureshi NS, Dujardin M, Ninot-Pedrosa M, Abele R, Abi Saad MJ, Alfano C, Almeida FCL, Alshamleh I, de Amorim GC, Anderson TK, Anobom CD, Anorma C, Bains JK, Bax A, Blackledge M, Blechar J, Böckmann A, Brigandat L, Bula A, Bütikofer M, Camacho-Zarco AR, Carlomagno T, Caruso IP, Ceylan B, Chaikuad A, Chu F, Cole L, Crosby MG, de Jesus V, Dhamotharan K, Felli IC, Ferner J, Fleischmann Y, Fogeron ML, Fourkiotis NK, Fuks C, Fürtig B, Gallo A, Gande SL, Gerez JA, Ghosh D, Gomes-Neto F, Gorbatyuk O, Guseva S, Hacker C, Häfner S, Hao B, Hargittay B, Henzler-Wildman K, Hoch JC, Hohmann KF, Hutchison MT, Jaudzems K, Jović K, Kaderli J, Kalniņš G, Kaņepe I, Kirchdoerfer RN, Kirkpatrick J, Knapp S, Krishnathas R, Kutz F, Zur Lage S, Lambertz R, Lang A, Laurents D, Lecoq L, Linhard V, Löhr F, Malki A, Bessa LM, Martin RW, Matzel T, Maurin D, McNutt SW, Mebus-Antunes NC, Meier BH, Meiser N, Mompeán M, Monaca E, Montserret R, Mariño Perez L, Moser C, Muhle-Goll C, Neves-Martins TC, Ni X, Norton-Baker B, Pierattelli R, Pontoriero L, Pustovalova Y, Ohlenschläger O, Orts J, Da Poian AT, Pyper DJ, Richter C, Riek R, Rienstra CM, Robertson A, Pinheiro AS, Sabbatella R, Salvi N, Saxena K, Schulte L, Schiavina M, Schwalbe H, Silber M, Almeida MDS, Sprague-Piercy MA, Spyroulias GA, Sreeramulu S, Tants JN, Tārs K, Torres F, Töws S, Treviño MÁ, Trucks S, Tsika AC, Varga K, Wang Y, Weber ME, Weigand JE, Wiedemann C, Wirmer-Bartoschek J, Wirtz Martin MA, Zehnder J, Hengesbach M, Schlundt A
Front Mol Biosci. 28.5.2021 8:653148. doi: 10.3389/fmolb.2021.653148
PMID: 34041264

Endogenous vitamin E metabolites mediate allosteric PPARγ activation with unprecedented co-regulatory interactions.
Willems S, Gellrich L, Chaikuad A, Kluge S, Werz O, Heering J, Knapp S, Lorkowski S, Schubert-Zsilavecz M, Merk D
Cell Chem Biol. 12.5.2021 . doi: 10.1016/j.chembiol.2021.04.019
PMID: 33989565

Structural Insights into Plasticity and Discovery of Remdesivir Metabolite GS-441524 Binding in SARS-CoV-2 Macrodomain.
Ni X, Schröder M, Olieric V, Sharpe ME, Hernandez-Olmos V, Proschak E, Merk D, Knapp S, Chaikuad A
ACS Med Chem Lett. 8.4.2021 12(4):603-609. doi: 10.1021/acsmedchemlett.0c00684
PMID: 33850605

7-(2-Anilinopyrimidin-4-yl)-1-benzazepin-2-ones Designed by a Cut and Glue Strategy Are Dual Aurora A/VEGF-R Kinase Inhibitors.
Karatas M, Chaikuad A, Berger B, Kubbutat MHG, Totzke F, Knapp S, Kunick C
Molecules. 14.3.2021 26(6):. doi: 10.3390/molecules26061611
PMID: 33799460

Oxaprozin Analogues as Selective RXR Agonists with Superior Properties and Pharmacokinetics.
Schierle S, Chaikuad A, Lillich FF, Ni X, Woltersdorf S, Schallmayer E, Renelt B, Ronchetti R, Knapp S, Proschak E, Merk D
J Med Chem. 1.4.2021 . doi: 10.1021/acs.jmedchem.1c00235
PMID: 33793232

Structure and Inhibitor Binding Characterization of Oncogenic MLLT1 Mutants.
Ni X, Londregan AT, Owen DR, Knapp S, Chaikuad A
ACS Chem Biol. 21.3.2021 . doi: 10.1021/acschembio.0c00960
PMID: 33749253

Highly selective inhibitors of protein kinases CLK and HIPK with the furo[3,2-b]pyridine core.
Němec V, Maier L, Berger BT, Chaikuad A, Drápela S, Souček K, Knapp S, Paruch K
Eur J Med Chem. 18.2.2021 215:113299. doi: 10.1016/j.ejmech.2021.113299
PMID: 33636538

2020

How to Separate Kinase Inhibition from Undesired Monoamine Oxidase A Inhibition-The Development of the DYRK1A Inhibitor AnnH75 from the Alkaloid Harmine.
Wurzlbauer A, Rüben K, Gürdal E, Chaikuad A, Knapp S, Sippl W, Becker W, Bracher F
Molecules. 16.12.2020 25(24):. doi: 10.3390/molecules25245962
PMID: 33339338

Discovery of a Novel Class of Covalent Dual Inhibitors Targeting the Protein Kinases BMX and BTK.
Forster M, Liang XJ, Schröder M, Gerstenecker S, Chaikuad A, Knapp S, Laufer S, Gehringer M
Int J Mol Sci. 4.12.2020 21(23):. doi: 10.3390/ijms21239269
PMID: 33291717

A Chemical Probe for Dark Kinase STK17B Derives Its Potency and High Selectivity through a Unique P-Loop Conformation.
Picado A, Chaikuad A, Wells CI, Shrestha S, Zuercher WJ, Pickett JE, Kwarcinski FE, Sinha P, de Silva CS, Zutshi R, Liu S, Kannan N, Knapp S, Drewry DH, Willson TM
J Med Chem. 20.11.2020 . doi: 10.1021/acs.jmedchem.0c01174
PMID: 33215924

Design, Synthesis, and Characterization of an Orally Active Dual-Specific ULK1/2 Autophagy Inhibitor that Synergizes with the PARP Inhibitor Olaparib for the Treatment of Triple-Negative Breast Cancer.
Ren H, Bakas NA, Vamos M, Chaikuad A, Limpert AS, Wimer CD, Brun SN, Lambert LJ, Tautz L, Celeridad M, Sheffler DJ, Knapp S, Shaw RJ, Cosford NDP
J Med Chem. 17.11.2020 . doi: 10.1021/acs.jmedchem.0c00873
PMID: 33200929

Comprehensive Set of Tertiary Complex Structures and Palmitic Acid Binding Provide Molecular Insights into Ligand Design for RXR Isoforms.
Chaikuad A, Pollinger J, Rühl M, Ni X, Kilu W, Heering J, Merk D
Int J Mol Sci. 11.11.2020 21(22):. doi: 10.3390/ijms21228457
PMID: 33187070

Crystal Structure and Inhibitor Identifications Reveal Targeting Opportunity for the Atypical MAPK Kinase ERK3.
Schröder M, Filippakopoulos P, Schwalm MP, Ferrer CA, Drewry DH, Knapp S, Chaikuad A
Int J Mol Sci. 26.10.2020 21(21):. doi: 10.3390/ijms21217953
PMID: 33114754

Chemical Starting Matter for HNF4α Ligand Discovery and Chemogenomics.
Meijer I, Willems S, Ni X, Heering J, Chaikuad A, Merk D
Int J Mol Sci. 24.10.2020 21(21):. doi: 10.3390/ijms21217895
PMID: 33114319

Design of new disubstituted imidazo[1,2-b]pyridazine derivatives as selective Haspin inhibitors. Synthesis, binding mode and anticancer biological evaluation.
Elie J, Feizbakhsh O, Desban N, Josselin B, Baratte B, Bescond A, Duez J, Fant X, Bach S, Marie D, Place M, Ben Salah S, Chartier A, Berteina-Raboin S, Chaikuad A, Knapp S, Carles F, Bonnet P, Buron F, Routier S, Ruchaud S
J Enzyme Inhib Med Chem. 13.10.2020 35(1):1840-1853. doi: 10.1080/14756366.2020.1825408
PMID: 33040634

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. 20.8.2020 208:112721. doi: 10.1016/j.ejmech.2020.112721
PMID: 33035818

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
Journal of Medicinal Chemistry. 11.08.2020 63:10224-10234. doi: 10.1021/acs.jmedchem.0c00898
PMID: 32787076

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.. 12.8.2020 . doi: 10.1021/acs.jmedchem.0c00898
PMID: 32787076

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. 4.8.2020 . doi: 10.1016/j.chembiol.2020.07.014
PMID: 32783966

Comparative structural analyses and nucleotide-binding characterization of the four KH domains of FUBP1.
Ni X, Knapp S, Chaikuad A
Sci Rep. 10.8.2020 10(1):13459. doi: 10.1038/s41598-020-69832-z
PMID: 32778776

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.. 15.5.2020 . doi: 10.2967/jnumed.120.243113
PMID: 32414951

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.. 1.5.2020 . doi: 10.1021/acs.jmedchem.9b02150
PMID: 32356658

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. 21.1.2020 11(1):419. doi: 10.1038/s41467-020-14299-9
PMID: 31964889

2019

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 Medicinal Chemistry Letters. 25.11.2019 10:1661-1666. doi: 10.1021/acsmedchemlett.9b00460
PMID: 31857843

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. 12.12.2019 10(12):1661-1666. doi: 10.1021/acsmedchemlett.9b00460
PMID: 31857843

Structural consequences of BMPR2 kinase domain mutations causing pulmonary arterial hypertension.
Chaikuad A, Thangaratnarajah C, von Delft F, Bullock AN
Sci Rep. 4.12.2019 9(1):18351. doi: 10.1038/s41598-019-54830-7
PMID: 31797984

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.. 8.11.2019 . doi: 10.1021/acs.jmedchem.9b01227
PMID: 31702918

Lessons from LIMK1 enzymology and their impact on inhibitor design
Salah E, Chatterjee D, Beltrami A, Tumber A, Preuss F, Canning P, Chaikuad A, Knaus P, Knapp S, Bullock AN, Mathea S
Biochemical Journal. 13.10.2019 476:3197-3209. doi: 10.1042/bcj20190517
PMID: 31652302

Lessons from LIMK1 enzymology and their impact on inhibitor design.
Salah E, Chatterjee D, Beltrami A, Tumber A, Preuss F, Canning P, Chaikuad A, Knaus P, Knapp S, Bullock AN, Mathea S
Biochem. J.. 14.10.2019 . doi: 10.1042/BCJ20190517
PMID: 31652302

Discovery of first in vivo active inhibitors of soluble epoxide hydrolase (sEH) phosphatase domain.
Kramer JS, Woltersdorf S, Duflot T, Hiesinger K, Lillich FF, Knöll F, Wittmann SK, Klingler FM, Brunst S, Chaikuad A, Morisseau C, Hammock BD, Buccellati C, Sala A, Rovati GE, Leuillier M, Fraineau S, Rondeaux J, Hernandez Olmos V, Heering J, Merk D, Pogoryelov D, Steinhilber D, Knapp S, Bellien J, Proschak E
J. Med. Chem.. 22.8.2019 . doi: 10.1021/acs.jmedchem.9b00445
PMID: 31436984

Leveraging Compound Promiscuity to Identify Targetable Cysteines within the Kinome.
Rao S, Gurbani D, Du G, Everley RA, Browne CM, Chaikuad A, Li T, Schröder M, Gondi S, Ficarro SB, Sim T, Kim ND, Berberich MJ, Knapp S, Marto JA, Westover KD, Sorger PK, Gray NS
Cell Chem Biol. 18.3.2019 . doi: 10.1016/j.chembiol.2019.02.021
PMID: 30982749

Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency
Heuberger K, Bailey HJ, Burda P, Chaikuad A, Krysztofinska E, Suormala T, Bürer C, Lutz S, Fowler B, Froese DS, Yue WW, Baumgartner MR
Biochimica et Biophysica Acta - Molecular Basis of Disease. 01.06.2019 1865:1265-1272. doi: 10.1016/j.bbadis.2019.01.021
PMID: 30682498

Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency.
Heuberger K, Bailey HJ, Burda P, Chaikuad A, Krysztofinska E, Suormala T, Bürer C, Lutz S, Fowler B, Froese DS, Yue WW, Baumgartner MR
Biochim Biophys Acta Mol Basis Dis. 22.1.2019 . doi: 10.1016/j.bbadis.2019.01.021
PMID: 30682498

2018

Furo[3,2-b]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway.
Němec V, Hylsová M, Maier L, Flegel J, Sievers S, Ziegler S, Schroeder M, Berger BT, Chaikuad A, Valčíková B, Uldrijan S, Drápela S, Souček K, Waldmann H, Knapp S, Paruch K
Angew. Chem. Int. Ed. Engl.. 20.12.2018 . doi: 10.1002/anie.201810312
PMID: 30569600

A structure-based approach towards identification of inhibitory fragments for eleven-nineteen-leukemia protein (ENL).
Heidenreich D, Moustakim M, Schmidt J, Merk D, Brennan PE, Fedorov O, Chaikuad A, Knapp S
J. Med. Chem.. 8.11.2018 . doi: 10.1021/acs.jmedchem.8b01457
PMID: 30407816

Discovery of an MLLT1/3 YEATS Domain Chemical Probe.
Moustakim M, Christott T, Monteiro OP, Bennett J, Giroud C, Ward J, Rogers CM, Smith P, Panagakou I, Saez LD, Felce SL, Gamble V, Gileadi C, Halidi N, Heidenreich D, Chaikuad A, Knapp S, Huber KVM, Farnie G, Heer J, Manevski N, Poda G, Al-Awar R, Dixon DJ, Fedorov O, Brennan P
Angew. Chem. Int. Ed. Engl.. 5.10.2018 . doi: 10.1002/anie.201810617
PMID: 30288907

Development, Optimization and Structure-Activity Relationships of Covalent-Reversible JAK3 Inhibitors Based on a Tricyclic Imidazo[5,4-d]pyrrolo[2,3-b]pyridine Scaffold.
Forster M, Chaikuad A, Dimitrov T, Döring E, Holstein J, Berger BT, Gehringer M, Ghoreschi K, Müller S, Knapp S, Laufer SA
J. Med. Chem.. 31.5.2018 . doi: 10.1021/acs.jmedchem.8b00571
PMID: 29852068

Molecular structures of cdc2-like kinases in complex with a new inhibitor chemotype.
Walter A, Chaikuad A, Helmer R, Loaëc N, Preu L, Ott I, Knapp S, Meijer L, Kunick C
PLoS ONE. 4.5.2018 13(5):e0196761. doi: 10.1371/journal.pone.0196761
PMID: 29723265

Halogen-aromatic π-interactions modulate inhibitor residence time.
Heroven C, Georgi V, Ganotra GK, Brennan PE, Wolfreys F, Wade RC, Fernández-Montalván AE, Chaikuad A, Knapp S
Angew. Chem. Int. Ed. Engl.. 30.3.2018 . doi: 10.1002/anie.201801666
PMID: 29601130

2017

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.. 18.10.2017 . doi: 10.1021/acschembio.7b00708
PMID: 29043777

Characterization of a highly selective inhibitor of the Aurora kinases.
Ferguson FM, Doctor ZM, Chaikuad A, Sim T, Kim ND, Knapp S, Gray NS
Bioorg. Med. Chem. Lett.. 10.8.2017 . doi: 10.1016/j.bmcl.2017.08.016
PMID: 28818446

Structures of PGAM5 Provide Insight into Active Site Plasticity and Multimeric Assembly.
Chaikuad A, Filippakopoulos P, Marcsisin SR, Picaud S, Schröder M, Sekine S, Ichijo H, Engen JR, Takeda K, Knapp S
Structure. 10.6.2017 . doi: 10.1016/j.str.2017.05.020
PMID: 28648608

A specific and covalent JNK-1 ligand selected from an encoded self-assembling chemical library.
Zimmermann G, Rieder U, Bajic D, Vanetti S, Chaikuad A, Knapp S, Scheuermann J, Mattarella M, Neri D
Chemistry. 9.5.2017 . doi: 10.1002/chem.201701644
PMID: 28485044

Development of potent, selective SRPK1 inhibitors as potential topical therapeutics for neovascular eye disease.
Batson J, Toop HD, Redondo C, Babaei-Jadidi R, Chaikuad A, Wearmouth SF, Gibbons B, Allen C, Tallant C, Zhang J, Du C, Hancox J, Hawtrey T, Da Rocha J, Griffith R, Knapp S, Bates DO, Morris JC
ACS Chem. Biol.. 30.1.2017 . doi: 10.1021/acschembio.6b01048
PMID: 28135068

2016

Identification of CLK1 Inhibitors by a Fragment-linking Based Virtual Screening.
Walter A, Chaikuad A, Loaëc N, Preu L, Knapp S, Meijer L, Kunick C, Koch O
Mol Inform. 21.12.2016 . doi: 10.1002/minf.201600123
PMID: 28000414

Discovery of New Bromodomain Scaffolds by Biosensor Fragment Screening.
Navratilova I, Aristotelous T, Picaud S, Chaikuad A, Knapp S, Filappakopoulos P, Hopkins AL
ACS Med Chem Lett. 8.12.2016 7(12):1213-1218. doi: 10.1021/acsmedchemlett.6b00154
PMID: 27994766

Discovery of a PCAF Bromodomain Chemical Probe.
Moustakim M, Clark PG, Trulli L, Fuentes de Arriba AL, Ehebauer MT, Chaikuad A, Murphy EJ, Mendez-Johnson J, Daniels D, Hou CD, Lin YH, Walker JR, Hui R, Yang H, Dorrell L, Rogers CM, Monteiro OP, Fedorov O, Huber KV, Knapp S, Heer J, Dixon DJ, Brennan PE
Angew. Chem. Int. Ed. Engl.. 14.12.2016 . doi: 10.1002/anie.201610816
PMID: 27966810

Selective JAK3 Inhibitors with a Covalent Reversible Binding Mode Targeting a New Induced Fit Binding Pocket.
Forster M, Chaikuad A, Bauer SM, Holstein J, Robers MB, Corona CR, Gehringer M, Pfaffenrot E, Ghoreschi K, Knapp S, Laufer SA
Cell Chem Biol. 7.11.2016 . doi: 10.1016/j.chembiol.2016.10.008
PMID: 27840070

An Unusual Binding Model of the Methyl 9-Anilinothiazolo[5,4-f] quinazoline-2-carbimidates (EHT 1610 and EHT 5372) Confers High Selectivity for Dual-specificity Tyrosine Phosphorylation-Regulated Kinases.
Chaikuad A, Diharce J, Schröder M, Foucourt A, Leblond B, Casagrande AS, Desire L, Bonnet P, Knapp S, Besson T
J. Med. Chem.. 21.10.2016 . doi: 10.1021/acs.jmedchem.6b01083
PMID: 27766861

Structural Basis of Intracellular TGF-β Signaling: Receptors and Smads.
Chaikuad A, Bullock AN
Cold Spring Harb Perspect Biol. 22.8.2016 . doi: 10.1101/cshperspect.a022111
PMID: 27549117

Co-crystal structures of the protein kinase haspin with bisubstrate inhibitors.
Lavogina D, Kestav K, Chaikuad A, Heroven C, Knapp S, Uri A
Acta Crystallogr F Struct Biol Commun. 1.5.2016 72(Pt 5):339-45. doi: 10.1107/S2053230X16004611
PMID: 27139824

Discovery of pyrido[3,4-g]quinazoline derivatives as CMGC family protein kinase inhibitors: Design, synthesis, inhibitory potency and X-ray co-crystal structure.
Esvan YJ, Zeinyeh W, Boibessot T, Nauton L, Théry V, Knapp S, Chaikuad A, Loaëc N, Meijer L, Anizon F, Giraud F, Moreau P
Eur J Med Chem. 5.4.2016 118:170-177. doi: 10.1016/j.ejmech.2016.04.004
PMID: 27128181

Structure-based identification of inhibitory fragments targeting the p300/CBP-associated factor bromodomain.
Chaikuad A, Lang S, Brennan PE, Temperini C, Fedorov O, Hollander J, Nachane R, Abell C, Müller S, Siegal G, Knapp S
J. Med. Chem.. 5.1.2016 . doi: 10.1021/acs.jmedchem.5b01719
PMID: 26731131

2015

The ins and outs of selective kinase inhibitor development.
Müller S, Chaikuad A, Gray NS, Knapp S
Nat. Chem. Biol.. 20.10.2015 11(11):818-21. doi: 10.1038/nchembio.1938
PMID: 26485069

Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells.
Morozumi Y, Boussouar F, Tan M, Chaikuad A, Jamshidikia M, Colak G, He H, Nie L, Petosa C, de Dieuleveult M, Curtet S, Vitte AL, Rabatel C, Debernardi A, Cosset FL, Verhoeyen E, Emadali A, Schweifer N, Gianni D, Gut M, Guardiola P, Rousseaux S, Gérard M, Knapp S, Zhao Y, Khochbin S
J Mol Cell Biol. 12.10.2015 . doi: 10.1093/jmcb/mjv060
PMID: 26459632

A core of kinase-regulated interactomes defines the neoplastic MDSC lineage.
Gato-Cañas M, Martinez de Morentin X, Blanco-Luquin I, Fernandez-Irigoyen J, Zudaire I, Liechtenstein T, Arasanz H, Lozano T, Casares N, Chaikuad A, Knapp S, Guerrero-Setas D, Escors D, Kochan G, Santamaría E
Oncotarget. 23.7.2015 . doi:
PMID: 26320174

Defined PEG smears as an alternative approach to enhance the search for crystallization conditions and crystal-quality improvement in reduced screens.
Chaikuad A, Knapp S, von Delft F
Acta Crystallogr. D Biol. Crystallogr.. 1.8.2015 71(Pt 8):1627-39. doi: 10.1107/S1399004715007968
PMID: 26249344

Selective inhibitors of Cyclin-G associated kinase (GAK) as anti-HCV agents.
Kovackova S, Chang L, Bekerman E, Neveu G, Barouch-Bentov R, Chaikuad A, Heroven C, Sala M, De Jonghe SC, Knapp S, Einav S, Herdewijn P
J. Med. Chem.. 30.3.2015 . doi: 10.1021/jm501759m
PMID: 25822739

Discovery and characterization of GSK2801, a selective chemical probe for the bromodomains BAZ2A and BAZ2B.
Chen P, Chaikuad A, Bamborough P, Bantscheff M, Bountra C, Chung CW, Fedorov O, Grandi P, Jung D, Lesniak R, Lindon M, Müller S, Philpott M, Prinjha RK, Rogers CM, Selenski C, Tallant C, Werner T, Willson TM, Knapp S, Drewry DH
J. Med. Chem.. 23.3.2015 . doi: 10.1021/acs.jmedchem.5b00209
PMID: 25799074

10-Iodo-11H-indolo[3,2-c]quinoline-6-carboxylic Acids Are Selective Inhibitors of DYRK1A.
Falke H, Chaikuad A, Becker A, Loaëc N, Lozach O, Abu Jhaisha S, Becker W, Jones PG, Preu L, Baumann K, Knapp S, Meijer L, Kunick C
J. Med. Chem.. 2.3.2015 . doi: 10.1021/jm501994d
PMID: 25730262

Structure Enabled Design of BAZ2-ICR, A Chemical Probe Targeting the Bromodomains of BAZ2A and BAZ2B.
Drouin L, McGrath S, Vidler LR, Chaikuad A, Monteiro O, Tallant C, Philpott M, Rogers C, Fedorov O, Liu M, Akhtar W, Hayes A, Raynaud F, Müller S, Knapp S, Hoelder S
J. Med. Chem.. 26.2.2015 . doi: 10.1021/jm501963e
PMID: 25719566

Bisubstrate Inhibitor Approach for Targeting Mitotic Kinase Haspin.
Kestav K, Lavogina D, Raidaru G, Chaikuad A, Knapp S, Uri A
Bioconjug. Chem.. 16.1.2015 . doi: 10.1021/bc500464r
PMID: 25595038

A small molecule targeting ALK1 prevents Notch cooperativity and inhibits functional angiogenesis.
Kerr G, Sheldon H, Chaikuad A, Alfano I, von Delft F, Bullock AN, Harris AL
Angiogenesis. 4.1.2015 . doi: 10.1007/s10456-014-9457-y
PMID: 25557927

2014

Small Molecules Dorsomorphin and LDN-193189 Inhibit Myostatin/GDF8 Signaling and Promote Functional Myoblast Differentiation.
Horbelt D, Boergermann JH, Chaikuad A, Alfano I, Williams E, Lukonin I, Timmel T, Bullock AN, Knaus P
J. Biol. Chem.. 3.11.2014 . doi: 10.1074/jbc.M114.604397
PMID: 25368322

A unique inhibitor binding site in ERK1/2 is associated with slow binding kinetics.
Chaikuad A, M C Tacconi E, Zimmer J, Liang Y, Gray NS, Tarsounas M, Knapp S
Nat. Chem. Biol.. 7.9.2014 . doi: 10.1038/nchembio.1629
PMID: 25195011

Modulation of the chromatin phosphoproteome by the Haspin protein kinase.
Maiolica A, De Medina Redondo M, Schoof EM, Chaikuad A, Villa F, Gatti M, Jeganatgan S, Lou HJ, Novy K, Hauri S, Toprak UH, Herzog F, Meraldi P, Penengo L, Turk BE, Knapp S, Linding R, Aebersold R
Mol. Cell Proteomics. 14.4.2014 . doi: 10.1074/mcp.M113.034819
PMID: 24732914

Copper is required for oncogenic BRAF signalling and tumorigenesis.
Brady DC, Crowe MS, Turski ML, Hobbs GA, Yao X, Chaikuad A, Knapp S, Xiao K, Campbell SL, Thiele DJ, Counter CM
Nature. 9.4.2014 . doi: 10.1038/nature13180
PMID: 24717435

Structure of Cyclin G associated kinase (GAK) Trapped in different Conformations using Nanobodies.
Chaikuad A, Keates T, Vincke C, Kaufholz M, Zenn M, Zimmermann B, Gutiérrez C, Zhang RG, Hatzos-Skintges C, Joachimiak A, Muyldermans S, Herberg FW, Knapp S, Müller S
Biochem. J.. 17.1.2014 . doi: 10.1042/BJ20131399
PMID: 24438162

2013

Targeting low-druggability bromodomains: Fragment based screening and inhibitor design against the BAZ2B bromodomain.
Ferguson FM, Fedorov O, Chaikuad A, Philpott M, Muniz J, Felletar I, von Delft F, Heightman TD, Knapp S, Abell C, Ciulli A
J. Med. Chem.. 4.12.2013 . doi: 10.1021/jm401582c
PMID: 24304323

Mechanism and consequence of the autoactivation of p38α mitogen-activated protein kinase promoted by TAB1.
De Nicola GF, Martin ED, Chaikuad A, Bassi R, Clark J, Martino L, Verma S, Sicard P, Tata R, Atkinson RA, Knapp S, Conte MR, Marber MS
Nat. Struct. Mol. Biol.. 15.9.2013 20(10):1182-1190. doi: 10.1038/nsmb.2668
PMID: 24037507

A New Class of Small Molecule Inhibitor of BMP Signaling.
Sanvitale CE, Kerr G, Chaikuad A, Ramel MC, Mohedas AH, Reichert S, Wang Y, Triffitt JT, Cuny GD, Yu PB, Hill CS, Bullock AN
PLoS ONE. 30.4.2013 8(4):e62721. doi: 10.1371/journal.pone.0062721
PMID: 23646137

Structural Basis for Cul3 Protein Assembly with the BTB-Kelch Family of E3 Ubiquitin Ligases.
Canning P, Cooper CD, Krojer T, Murray JW, Pike AC, Chaikuad A, Keates T, Thangaratnarajah C, Hojzan V, Marsden BD, Gileadi O, Knapp S, von Delft F, Bullock AN
J. Biol. Chem.. 15.3.2013 288(11):7803-14. doi: 10.1074/jbc.M112.437996
PMID: 23349464

2012

Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva.
Chaikuad A, Alfano I, Kerr G, Sanvitale CE, Boergermann JH, Triffitt JT, von Delft F, Knapp S, Knaus P, Bullock AN
J. Biol. Chem.. 26.10.2012 287(44):36990-8. doi: 10.1074/jbc.M112.365932
PMID: 22977237

Structure of human aspartyl aminopeptidase complexed with substrate analogue: insight into catalytic mechanism, substrate specificity and M18 peptidase family.
Chaikuad A, Pilka ES, De Riso A, von Delft F, Kavanagh KL, Vénien-Bryan C, Oppermann U, Yue WW
BMC Struct. Biol.. 21.6.2012 12:14. doi: 10.1186/1472-6807-12-14
PMID: 22720794

Structural and kinetic evidence that catalytic reaction of human UDP-glucose 6-dehydrogenase involves covalent thiohemiacetal and thioester enzyme intermediates.
Egger S, Chaikuad A, Klimacek M, Kavanagh KL, Oppermann U, Nidetzky B
J. Biol. Chem.. 13.1.2012 287(3):2119-29. doi: 10.1074/jbc.M111.313015
PMID: 22123821

2011

Conformational plasticity of glycogenin and its maltosaccharide substrate during glycogen biogenesis.
Chaikuad A, Froese DS, Berridge G, von Delft F, Oppermann U, Yue WW
Proc. Natl. Acad. Sci. U.S.A.. 27.12.2011 108(52):21028-33. doi: 10.1073/pnas.1113921108
PMID: 22160680

Structure and mechanism of human UDP-glucose 6-dehydrogenase.
Egger S, Chaikuad A, Kavanagh KL, Oppermann U, Nidetzky B
J. Biol. Chem.. 8.7.2011 286(27):23877-87. doi: 10.1074/jbc.M111.234682
PMID: 21502315

Structure and kinetic characterization of human sperm-specific glyceraldehyde-3-phosphate dehydrogenase, GAPDS.
Chaikuad A, Shafqat N, Al-Mokhtar R, Cameron G, Clarke AR, Brady RL, Oppermann U, Frayne J, Yue WW
Biochem. J.. 15.4.2011 435(2):401-9. doi: 10.1042/BJ20101442
PMID: 21269272

2010

UDP-glucose dehydrogenase: structure and function of a potential drug target.
Egger S, Chaikuad A, Kavanagh KL, Oppermann U, Nidetzky B
Biochem. Soc. Trans.. 25.9.2010 38(5):1378-85. doi: 10.1042/BST0381378
PMID: 20863317

Structural comparison of human mammalian ste20-like kinases.
Record CJ, Chaikuad A, Rellos P, Das S, Pike AC, Fedorov O, Marsden BD, Knapp S, Lee WH
PLoS ONE. 6.8.2010 5(8):e11905. doi: 10.1371/journal.pone.0011905
PMID: 20730082

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