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Natural-product-derived fragments for fragment-based ligand discovery.

Over B, Wetzel S, Grütter C, Nakai Y, Renner S, Rauh D, Waldmann H
Nat Chem 5 21-8 (2013)
Related entries: 4eh2, 4eh3, 4eh5, 4eh6, 4eh7, 4eh8, 4eh9, 4ehv

Cited: 114 times
EuropePMC logo PMID: 23247173

Abstract

Fragment-based ligand and drug discovery predominantly employs sp(2)-rich compounds covering well-explored regions of chemical space. Despite the ease with which such fragments can be coupled, this focus on flat compounds is widely cited as contributing to the attrition rate of the drug discovery process. In contrast, biologically validated natural products are rich in stereogenic centres and populate areas of chemical space not occupied by average synthetic molecules. Here, we have analysed more than 180,000 natural product structures to arrive at 2,000 clusters of natural-product-derived fragments with high structural diversity, which resemble natural scaffolds and are rich in sp(3)-configured centres. The structures of the cluster centres differ from previously explored fragment libraries, but for nearly half of the clusters representative members are commercially available. We validate their usefulness for the discovery of novel ligand and inhibitor types by means of protein X-ray crystallography and the identification of novel stabilizers of inactive conformations of p38α MAP kinase and of inhibitors of several phosphatases.

Articles - 4eh4 mentioned but not cited (2)

  1. p38α Mitogen-Activated Protein Kinase Is a Druggable Target in Pancreatic Adenocarcinoma. Yang L, Sun X, Ye Y, Lu Y, Zuo J, Liu W, Elcock A, Zhu S. Front Oncol 9 1294 (2019)
  2. p38α MAPK and Type I Inhibitors: Binding Site Analysis and Use of Target Ensembles in Virtual Screening. Astolfi A, Iraci N, Sabatini S, Barreca ML, Cecchetti V. Molecules 20 15842-15861 (2015)


Reviews citing this publication (31)

  1. Counting on natural products for drug design. Rodrigues T, Reker D, Schneider P, Schneider G. Nat Chem 8 531-541 (2016)
  2. Twenty years on: the impact of fragments on drug discovery. Erlanson DA, Fesik SW, Hubbard RE, Jahnke W, Jhoti H. Nat Rev Drug Discov 15 605-619 (2016)
  3. Ten things you should know about protein kinases: IUPHAR Review 14. Fabbro D, Cowan-Jacob SW, Moebitz H. Br J Pharmacol 172 2675-2700 (2015)
  4. Multi-target approach for natural products in inflammation. Koeberle A, Werz O. Drug Discov Today 19 1871-1882 (2014)
  5. Strategies to diversify natural products for drug discovery. Li G, Lou HX. Med Res Rev 38 1255-1294 (2018)
  6. Principle and design of pseudo-natural products. Karageorgis G, Foley DJ, Laraia L, Waldmann H. Nat Chem 12 227-235 (2020)
  7. Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis. Crane EA, Gademann K. Angew Chem Int Ed Engl 55 3882-3902 (2016)
  8. Strategies for the Optimization of Natural Leads to Anticancer Drugs or Drug Candidates. Xiao Z, Morris-Natschke SL, Lee KH. Med Res Rev 36 32-91 (2016)
  9. The impact of in silico screening in the discovery of novel and safer drug candidates. Rognan D. Pharmacol Ther 175 47-66 (2017)
  10. Evolution of In Silico Strategies for Protein-Protein Interaction Drug Discovery. Macalino SJY, Basith S, Clavio NAB, Chang H, Kang S, Choi S. Molecules 23 E1963 (2018)
  11. Developing new antibacterials through natural product research. Kirst HA. Expert Opin Drug Discov 8 479-493 (2013)
  12. Design, Synthesis, and Phenotypic Profiling of Pyrano-Furo-Pyridone Pseudo Natural Products. Christoforow A, Wilke J, Binici A, Pahl A, Ostermann C, Sievers S, Waldmann H. Angew Chem Int Ed Engl 58 14715-14723 (2019)
  13. History, biology and chemistry of Mycobacterium ulcerans infections (Buruli ulcer disease). Chany AC, Tresse C, Casarotto V, Blanchard N. Nat Prod Rep 30 1527-1567 (2013)
  14. Recent advances in the chemistry of metallated azetidines. Antermite D, Degennaro L, Luisi R. Org Biomol Chem 15 34-50 (2016)
  15. Pseudo Natural Products-Chemical Evolution of Natural Product Structure. Karageorgis G, Foley DJ, Laraia L, Brakmann S, Waldmann H. Angew Chem Int Ed Engl 60 15705-15723 (2021)
  16. Applications of Virtual Screening in Bioprospecting: Facts, Shifts, and Perspectives to Explore the Chemo-Structural Diversity of Natural Products. Santana K, do Nascimento LD, Lima E Lima A, Damasceno V, Nahum C, Braga RC, Lameira J. Front Chem 9 662688 (2021)
  17. Development of Glucose Transporter (GLUT) Inhibitors. Reckzeh ES, Waldmann H. European J Org Chem 2020 2321-2329 (2020)
  18. Plant polyphenols in the treatment of age-associated diseases: revealing the pleiotropic effects of icariin by network analysis. Schluesener JK, Schluesener H. Mol Nutr Food Res 58 49-60 (2014)
  19. Current status and prospects of computational resources for natural product dereplication: a review. Mohamed A, Nguyen CH, Mamitsuka H. Brief Bioinform 17 309-321 (2016)
  20. Structural simplification: an efficient strategy in lead optimization. Wang S, Dong G, Sheng C. Acta Pharm Sin B 9 880-901 (2019)
  21. Harnessing the potential of natural products in drug discovery from a cheminformatics vantage point. Rodrigues T. Org Biomol Chem 15 9275-9282 (2017)
  22. Fragment-based screening with natural products for novel anti-parasitic disease drug discovery. Liu M, Quinn RJ. Expert Opin Drug Discov 14 1283-1295 (2019)
  23. The use of natural products in colorectal cancer drug discovery. Miura K, Satoh M, Kinouchi M, Yamamoto K, Hasegawa Y, Kakugawa Y, Kawai M, Uchimi K, Aizawa H, Ohnuma S, Kajiwara T, Sakurai H, Fujiya T. Expert Opin Drug Discov 10 411-426 (2015)
  24. A Comprehensive Structural Overview of p38α MAPK in Complex with Type I Inhibitors. Astolfi A, Iraci N, Manfroni G, Barreca ML, Cecchetti V. ChemMedChem 10 957-969 (2015)
  25. Advances in the design of a multipurpose fragment screening library. Wilde F, Link A. Expert Opin Drug Discov 8 597-606 (2013)
  26. The Time and Place for Nature in Drug Discovery. Young RJ, Flitsch SL, Grigalunas M, Leeson PD, Quinn RJ, Turner NJ, Waldmann H. JACS Au 2 2400-2416 (2022)
  27. Natural product-informed exploration of chemical space to enable bioactive molecular discovery. Nelson A, Karageorgis G. RSC Med Chem 12 353-362 (2021)
  28. Bacteria as genetically programmable producers of bioactive natural products. Hug JJ, Krug D, Müller R. Nat Rev Chem 4 172-193 (2020)
  29. Macrocycles in Drug Discovery─Learning from the Past for the Future. Garcia Jimenez D, Poongavanam V, Kihlberg J. J Med Chem 66 5377-5396 (2023)
  30. Computational Approaches to Enzyme Inhibition by Marine Natural Products in the Search for New Drugs. Gago F. Mar Drugs 21 100 (2023)
  31. High-Throughput Screening of Natural Product and Synthetic Molecule Libraries for Antibacterial Drug Discovery. Ayon NJ. Metabolites 13 625 (2023)

Articles citing this publication (81)

  1. The 'rule of three' for fragment-based drug discovery: where are we now? Jhoti H, Williams G, Rees DC, Murray CW. Nat Rev Drug Discov 12 644-645 (2013)
  2. A three-stage biophysical screening cascade for fragment-based drug discovery. Mashalidis EH, Śledź P, Lang S, Abell C. Nat Protoc 8 2309-2324 (2013)
  3. Revealing the macromolecular targets of complex natural products. Reker D, Perna AM, Rodrigues T, Schneider P, Reutlinger M, Mönch B, Koeberle A, Lamers C, Gabler M, Steinmetz H, Müller R, Schubert-Zsilavecz M, Werz O, Schneider G. Nat Chem 6 1072-1078 (2014)
  4. Assembly and clustering of natural antibiotics guides target identification. Johnston CW, Skinnider MA, Dejong CA, Rees PN, Chen GM, Walker CG, French S, Brown ED, Bérdy J, Liu DY, Magarvey NA. Nat Chem Biol 12 233-239 (2016)
  5. Opportunity Knocks: Organic Chemistry for Fragment-Based Drug Discovery (FBDD). Murray CW, Rees DC. Angew Chem Int Ed Engl 55 488-492 (2016)
  6. Novel approaches for targeting kinases: allosteric inhibition, allosteric activation and pseudokinases. Cowan-Jacob SW, Jahnke W, Knapp S. Future Med Chem 6 541-561 (2014)
  7. Discovery of Ganoderma lucidum triterpenoids as potential inhibitors against Dengue virus NS2B-NS3 protease. Bharadwaj S, Lee KE, Dwivedi VD, Yadava U, Panwar A, Lucas SJ, Pandey A, Kang SG. Sci Rep 9 19059 (2019)
  8. Iterative protecting group-free cross-coupling leading to chiral multiply arylated structures. Crudden CM, Ziebenhaus C, Rygus JP, Ghozati K, Unsworth PJ, Nambo M, Voth S, Hutchinson M, Laberge VS, Maekawa Y, Imao D. Nat Commun 7 11065 (2016)
  9. Chromopynones are pseudo natural product glucose uptake inhibitors targeting glucose transporters GLUT-1 and -3. Karageorgis G, Reckzeh ES, Ceballos J, Schwalfenberg M, Sievers S, Ostermann C, Pahl A, Ziegler S, Waldmann H. Nat Chem 10 1103-1111 (2018)
  10. 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 R, Nguyen B, Andrews KT, Skinner-Adams T, Kim J, Hol WGJ, Hui R, Crowther GJ, Van Voorhis WC, Quinn RJ. ACS Infect Dis 4 431-444 (2018)
  11. Synthesis of Indomorphan Pseudo-Natural Product Inhibitors of Glucose Transporters GLUT-1 and -3. Ceballos J, Schwalfenberg M, Karageorgis G, Reckzeh ES, Reckzeh ES, Sievers S, Ostermann C, Pahl A, Sellstedt M, Nowacki J, Carnero Corrales MA, Wilke J, Laraia L, Tschapalda K, Metz M, Sehr DA, Brand S, Winklhofer K, Janning P, Ziegler S, Waldmann H. Angew Chem Int Ed Engl 58 17016-17025 (2019)
  12. Catalytic enantioselective synthesis of functionalized tropanes reveals novel inhibitors of hedgehog signaling. Narayan R, Bauer JO, Strohmann C, Antonchick AP, Waldmann H. Angew Chem Int Ed Engl 52 12892-12896 (2013)
  13. Liganding Functional Tyrosine Sites on Proteins Using Sulfur-Triazole Exchange Chemistry. Brulet JW, Borne AL, Yuan K, Libby AH, Hsu KL. J Am Chem Soc 142 8270-8280 (2020)
  14. Yeast synthetic biology platform generates novel chemical structures as scaffolds for drug discovery. Klein J, Heal JR, Hamilton WD, Boussemghoune T, Tange TØ, Delegrange F, Jaeschke G, Hatsch A, Heim J. ACS Synth Biol 3 314-323 (2014)
  15. Increasing chemical space coverage by combining empirical and computational fragment screens. Barelier S, Eidam O, Fish I, Hollander J, Figaroa F, Nachane R, Irwin JJ, Shoichet BK, Siegal G. ACS Chem Biol 9 1528-1535 (2014)
  16. Charting Biologically Relevant Spirocyclic Compound Space. Müller G, Berkenbosch T, Benningshof JC, Stumpfe D, Bajorath J. Chemistry 23 703-710 (2017)
  17. Chemical Evolution of Natural Product Structure. Grigalunas M, Brakmann S, Waldmann H. J Am Chem Soc 144 3314-3329 (2022)
  18. On the origins of three-dimensionality in drug-like molecules. Meyers J, Carter M, Mok NY, Brown N. Future Med Chem 8 1753-1767 (2016)
  19. Design and Synthesis of 56 Shape-Diverse 3D Fragments. Downes TD, Jones SP, Klein HF, Wheldon MC, Atobe M, Bond PS, Firth JD, Chan NS, Waddelove L, Hubbard RE, Blakemore DC, De Fusco C, Roughley SD, Vidler LR, Whatton MA, Woolford AJ, Wrigley GL, O'Brien P. Chemistry 26 8969-8975 (2020)
  20. Capturing nature's diversity. Pascolutti M, Campitelli M, Nguyen B, Pham N, Gorse AD, Quinn RJ. PLoS One 10 e0120942 (2015)
  21. DNA display of fragment pairs as a tool for the discovery of novel biologically active small molecules. Daguer JP, Zambaldo C, Ciobanu M, Morieux P, Barluenga S, Winssinger N. Chem Sci 6 739-744 (2015)
  22. Synthetic biology based construction of biological activity-related library of fungal decalin-containing diterpenoid pyrones. Tsukada K, Shinki S, Kaneko A, Murakami K, Irie K, Murai M, Miyoshi H, Dan S, Kawaji K, Hayashi H, Kodama EN, Hori A, Salim E, Kuraishi T, Hirata N, Kanda Y, Asai T. Nat Commun 11 1830 (2020)
  23. Highly enantioselective catalytic synthesis of neurite growth-promoting secoyohimbanes. Antonchick AP, López-Tosco S, Parga J, Sievers S, Schürmann M, Preut H, Höing S, Schöler HR, Sterneckert J, Rauh D, Waldmann H. Chem Biol 20 500-509 (2013)
  24. Revealing the Macromolecular Targets of Fragment-Like Natural Products. Rodrigues T, Reker D, Kunze J, Schneider P, Schneider G. Angew Chem Int Ed Engl 54 10516-10520 (2015)
  25. Synthesis and Demonstration of the Biological Relevance of sp3 -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 23 15227-15232 (2017)
  26. Catalytic asymmetric exo-selective [6+3] cycloaddition of iminoesters with fulvenes. Potowski M, Antonchick AP, Waldmann H. Chem Commun (Camb) 49 7800-7802 (2013)
  27. Understanding the foundations of the structural similarities between marketed drugs and endogenous human metabolites. O'Hagan S, Kell DB. Front Pharmacol 6 105 (2015)
  28. Construction of a 3D-shaped, natural product like fragment library by fragmentation and diversification of natural products. Prescher H, Koch G, Schuhmann T, Ertl P, Bussenault A, Glick M, Dix I, Petersen F, Lizos DE. Bioorg Med Chem 25 921-925 (2017)
  29. Dehydrogenative reagent-free annulation of alkenes with diols for the synthesis of saturated O-heterocycles. Cai CY, Xu HC. Nat Commun 9 3551 (2018)
  30. Phenotyping Reveals Targets of a Pseudo-Natural-Product Autophagy Inhibitor. Foley DJ, Zinken S, Corkery D, Laraia L, Pahl A, Wu YW, Waldmann H. Angew Chem Int Ed Engl 59 12470-12476 (2020)
  31. Exploring protein hotspots by optimized fragment pharmacophores. Bajusz D, Wade WS, Satała G, Bojarski AJ, Ilaš J, Ebner J, Grebien F, Papp H, Jakab F, Douangamath A, Fearon D, von Delft F, Schuller M, Ahel I, Wakefield A, Vajda S, Gerencsér J, Pallai P, Keserű GM. Nat Commun 12 3201 (2021)
  32. Halogen-enriched fragment libraries as chemical probes for harnessing halogen bonding in fragment-based lead discovery. Zimmermann MO, Lange A, Wilcken R, Cieslik MB, Exner TE, Joerger AC, Koch P, Boeckler FM. Future Med Chem 6 617-639 (2014)
  33. Highly Enantioselective Catalytic Vinylogous Propargylation of Coumarins Yields a Class of Autophagy Inhibitors. Xu H, Laraia L, Schneider L, Louven K, Strohmann C, Antonchick AP, Waldmann H. Angew Chem Int Ed Engl 56 11232-11236 (2017)
  34. Merging allosteric and active site binding motifs: de novo generation of target selectivity and potency via natural-product-derived fragments. Lanz J, Riedl R. ChemMedChem 10 451-454 (2015)
  35. Partially Saturated Bicyclic Heteroaromatics as an sp(3) -Enriched Fragment Collection. Twigg DG, Kondo N, Mitchell SL, Galloway WR, Sore HF, Madin A, Spring DR. Angew Chem Int Ed Engl 55 12479-12483 (2016)
  36. UHPLC-ESI-QTOF-MS/MS-Based Molecular Networking Guided Isolation and Dereplication of Antibacterial and Antifungal Constituents of Ventilago denticulata. Azizah M, Pripdeevech P, Thongkongkaew T, Mahidol C, Ruchirawat S, Kittakoop P. Antibiotics (Basel) 9 E606 (2020)
  37. Comparative analysis of chemical similarity methods for modular natural products with a hypothetical structure enumeration algorithm. Skinnider MA, Dejong CA, Franczak BC, McNicholas PD, Magarvey NA. J Cheminform 9 46 (2017)
  38. Natural product fragment combination to performance-diverse pseudo-natural products. Grigalunas M, Burhop A, Zinken S, Pahl A, Gally JM, Wild N, Mantel Y, Sievers S, Foley DJ, Scheel R, Strohmann C, Antonchick AP, Waldmann H. Nat Commun 12 1883 (2021)
  39. Design, Synthesis, and Biological Evaluation of Chemically and Biologically Diverse Pyrroquinoline Pseudo Natural Products. Liu J, Cremosnik GS, Otte F, Pahl A, Sievers S, Strohmann C, Waldmann H. Angew Chem Int Ed Engl 60 4648-4656 (2021)
  40. Comment Drug discovery: nature's pieces. Shoichet BK. Nat Chem 5 9-10 (2013)
  41. Palladium-Catalyzed Directed C(sp3)-H Arylation of Saturated Heterocycles at C-3 Using a Concise Optimization Approach. Affron DP, Bull JA. European J Org Chem 2016 139-149 (2016)
  42. Macrocyclic Modalities Combining Peptide Epitopes and Natural Product Fragments. Guéret SM, Thavam S, Carbajo RJ, Potowski M, Larsson N, Dahl G, Dellsén A, Grossmann TN, Plowright AT, Valeur E, Lemurell M, Waldmann H. J Am Chem Soc 142 4904-4915 (2020)
  43. Mining Natural Products for Macrocycles to Drug Difficult Targets. Begnini F, Poongavanam V, Over B, Castaldo M, Geschwindner S, Johansson P, Tyagi M, Tyrchan C, Wissler L, Sjö P, Schiesser S, Kihlberg J. J Med Chem 64 1054-1072 (2021)
  44. Synthesis of bridged diketopiperazines by using the persistent radical effect and a formal synthesis of bicyclomycin. Amatov T, Pohl R, Císařová I, Jahn U. Angew Chem Int Ed Engl 54 12153-12157 (2015)
  45. Re-engineering natural products to engage new biological targets. Motika SE, Hergenrother PJ. Nat Prod Rep 37 1395-1403 (2020)
  46. Construction of a Shape-Diverse Fragment Set: Design, Synthesis and Screen against Aurora-A Kinase. Zhang R, McIntyre PJ, Collins PM, Foley DJ, Arter C, von Delft F, Bayliss R, Warriner S, Nelson A. Chemistry 25 6831-6839 (2019)
  47. Enantiodivergent Combination of Natural Product Scaffolds Enabled by Catalytic Enantioselective Cycloaddition. Xu H, Golz C, Strohmann C, Antonchick AP, Waldmann H. Angew Chem Int Ed Engl 55 7761-7765 (2016)
  48. Editorial Extending accessible chemical space for the identification of novel leads. Bajorath J. Expert Opin Drug Discov 11 825-829 (2016)
  49. Combination of Pseudo-Natural Product Design and Formal Natural Product Ring Distortion Yields Stereochemically and Biologically Diverse Pseudo-Sesquiterpenoid Alkaloids. Liu J, Flegel J, Otte F, Pahl A, Sievers S, Strohmann C, Waldmann H. Angew Chem Int Ed Engl 60 21384-21395 (2021)
  50. A general catalytic reaction sequence to access alkaloid-inspired indole polycycles. Danda A, Kumar K, Waldmann H. Chem Commun (Camb) 51 7536-7539 (2015)
  51. A natural-product switch for a dynamic protein interface. Scheepstra M, Nieto L, Hirsch AK, Fuchs S, Leysen S, Lam CV, in het Panhuis L, van Boeckel CA, Wienk H, Boelens R, Ottmann C, Milroy LG, Brunsveld L. Angew Chem Int Ed Engl 53 6443-6448 (2014)
  52. Comprehensive analysis of commercial fragment libraries. Revillo Imbernon J, Jacquemard C, Bret G, Marcou G, Kellenberger E. RSC Med Chem 13 300-310 (2022)
  53. Drug discovery: a modern decathlon. Laufer S, Holzgrabe U, Steinhilber D. Angew Chem Int Ed Engl 52 4072-4076 (2013)
  54. Increasing the coverage of medicinal chemistry-relevant space in commercial fragments screening. Mok NY, Brenk R, Brown N. J Chem Inf Model 54 79-85 (2014)
  55. Synthesis of Indofulvin Pseudo-Natural Products Yields a New Autophagy Inhibitor Chemotype. Burhop A, Bag S, Grigalunas M, Woitalla S, Bodenbinder P, Brieger L, Strohmann C, Pahl A, Sievers S, Waldmann H. Adv Sci (Weinh) 8 e2102042 (2021)
  56. Alkaloid inspired spirocyclic oxindoles from 1,3-dipolar cycloaddition of pyridinium ylides. Day J, Uroos M, Castledine RA, Lewis W, McKeever-Abbas B, Dowden J. Org Biomol Chem 11 6502-6509 (2013)
  57. Catalytic promiscuity of the non-native FPP substrate in the TEAS enzyme: non-negligible flexibility of the carbocation intermediate. Zhang F, Wang YH, Tang X, Wu R. Phys Chem Chem Phys 20 15061-15073 (2018)
  58. Towards the Next Generation of Computational Chemogenomics Tools. Rognan D. Mol Inform 32 1029-1034 (2013)
  59. Translational synthetic chemistry. Kesavan S, Marcaurelle LA. Nat Chem Biol 9 210-213 (2013)
  60. Biofragments: an approach towards predicting protein function using biologically related fragments and its application to Mycobacterium tuberculosis CYP126. Hudson SA, Mashalidis EH, Bender A, McLean KJ, Munro AW, Abell C. Chembiochem 15 549-555 (2014)
  61. Catalytic aerobic oxidation and tandem enantioselective cycloaddition in cascade multicomponent synthesis. Potowski M, Merten C, Antonchick AP, Waldmann H. Chemistry 21 4913-4917 (2015)
  62. Conformational diversity in contryphans from Conus venom: cis-trans isomerisation and aromatic/proline interactions in the 23-membered ring of a 7-residue peptide disulfide loop. Sonti R, Gowd KH, Rao KN, Ragothama S, Rodriguez A, Perez JJ, Balaram P. Chemistry 19 15175-15189 (2013)
  63. Divergent response of homologous ATP sites to stereospecific ligand fluorination for selectivity enhancement. Patel AR, Hardianto A, Ranganathan S, Liu F. Org Biomol Chem 15 1570-1574 (2017)
  64. Exploring and mapping chemical space with molecular assembly trees. Liu Y, Mathis C, Bajczyk MD, Marshall SM, Wilbraham L, Cronin L. Sci Adv 7 eabj2465 (2021)
  65. Pseudonatural Products Occur Frequently in Biologically Relevant Compounds. Gally JM, Pahl A, Czodrowski P, Waldmann H. J Chem Inf Model 61 5458-5468 (2021)
  66. Inhibitors of Human Divalent Metal Transporters DMT1 (SLC11A2) and ZIP8 (SLC39A8) from a GDB-17 Fragment Library. Pujol-Giménez J, Poirier M, Bühlmann S, Schuppisser C, Bhardwaj R, Awale M, Visini R, Javor S, Hediger MA, Reymond JL. ChemMedChem 16 3306-3314 (2021)
  67. Multicomponent Synthesis of Polyphenols and their in vitro Evaluation as Potential β-Amyloid Aggregation Inhibitors. Galante D, Banfi L, Baruzzo G, Basso A, D'Arrigo C, Lunaccio D, Moni L, Riva R, Lambruschini C. Molecules 24 E2636 (2019)
  68. The Pseudo-Natural Product Rhonin Targets RHOGDI. Akbarzadeh M, Flegel J, Patil S, Shang E, Narayan R, Buchholzer M, Kazemein Jasemi NS, Grigalunas M, Krzyzanowski A, Abegg D, Shuster A, Potowski M, Karatas H, Karageorgis G, Mosaddeghzadeh N, Zischinsky ML, Merten C, Golz C, Brieger L, Strohmann C, Antonchick AP, Janning P, Adibekian A, Goody RS, Ahmadian MR, Ziegler S, Waldmann H. Angew Chem Int Ed Engl 61 e202115193 (2022)
  69. Identification of Small Molecule Inhibitors of RNase L by Fragment-Based Drug Discovery. Tang J, Dong B, Liu M, Liu S, Niu X, Gaughan C, Asthana A, Zhou H, Xu Z, Zhang G, Silverman RH, Huang H. J Med Chem 65 1445-1457 (2022)
  70. Polymer supported synthesis of a natural product-inspired oxepane library. Basu S, Waldmann H. Bioorg Med Chem 22 4430-4444 (2014)
  71. Synthesis of 20-Membered Macrocyclic Pseudo-Natural Products Yields Inducers of LC3 Lipidation. Niggemeyer G, Knyazeva A, Gasper R, Corkery D, Bodenbinder P, Holstein JJ, Sievers S, Wu YW, Waldmann H. Angew Chem Int Ed Engl 61 e202114328 (2022)
  72. Unprecedented Combination of Polyketide Natural Product Fragments Identifies the New Hedgehog Signaling Pathway Inhibitor Grismonone. Grigalunas M, Patil S, Krzyzanowski A, Pahl A, Flegel J, Schölermann B, Xie J, Sievers S, Ziegler S, Waldmann H. Chemistry 28 e202202164 (2022)
  73. (-)-Cytisine: Access to a stereochemically defined and functionally flexible piperidine scaffold. Niwetmarin W, Rego Campello H, Sparkes HA, Aggarwal VK, Gallagher T. Org Biomol Chem 16 5823-5832 (2018)
  74. Identification of a Novel Pseudo-Natural Product Type IV IDO1 Inhibitor Chemotype. Davies C, Dötsch L, Ciulla MG, Hennes E, Yoshida K, Gasper R, Scheel R, Sievers S, Strohmann C, Kumar K, Ziegler S, Waldmann H. Angew Chem Int Ed Engl 61 e202209374 (2022)
  75. Non-Extensive Fragmentation of Natural Products and Pharmacophore-Based Virtual Screening as a Practical Approach to Identify Novel Promising Chemical Scaffolds. Vásquez AF, Muñoz AR, Duitama J, González Barrios A. Front Chem 9 700802 (2021)
  76. QSAR and Molecular Docking Studies of Pyrimidine-Coumarin-Triazole Conjugates as Prospective Anti-Breast Cancer Agents. Subramani AK, Sivaperuman A, Natarajan R, Bhandare RR, Shaik AB. Molecules 27 1845 (2022)
  77. Research Support, Non-U.S. Gov't What is the future for fragment-based drug discovery? Keserű GM, Hann MM. Future Med Chem 9 1457-1460 (2017)
  78. A highly enantioselective intramolecular 1,3-dipolar cycloaddition yields novel pseudo-natural product inhibitors of the Hedgehog signalling pathway. Liu J, Zhang R, Mallick S, Patil S, Wientjens C, Flegel J, Krupp A, Strohmann C, Grassin C, Merten C, Pahl A, Grigalunas M, Waldmann H. Chem Sci 14 7936-7943 (2023)
  79. Green Drug Discovery: Novel Fragment Space from the Biomass-Derived Molecule Dihydrolevoglucosenone (CyreneTM). Dekker T, Harteveld JW, Wágner G, de Vries MCM, Custers H, van de Stolpe AC, de Esch IJP, Wijtmans M. Molecules 28 1777 (2023)
  80. Marine furanocembranoids-inspired macrocycles enabled by Pd-catalyzed unactivated C(sp3)-H olefination mediated by donor/donor carbenes. Hao J, Guo X, He S, Xu Z, Chen L, Li Z, Song B, Zuo J, Lin Z, Yang W. Nat Commun 12 1304 (2021)
  81. Reverse Biosynthesis: Generating Combinatorial Pools of Drug Leads from Enzyme-Mediated Fragmentation of Natural Products. Richardson-Sanchez T, Tieu W, Codd R. Chembiochem 18 368-373 (2017)


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