Fragment-to-Lead Medicinal Chemistry Publications in 2015

Journal of Medicinal Chemistry

Volumn 60, Issue 1, 2017, Pages 89-99

  Johnson, Christopher N ^a   Erlanson, Daniel A ^b   Murray, Christopher W ^a   Rees, David C ^a  

^a ASTEX PHARMACEUTICALS   (United Kingdom)

^b Carmot Therapeutics Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN KINASE INHIBITOR;

BINDING AFFINITY; BIOTECHNOLOGY; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG POTENCY; DRUG SCREENING; DRUG TARGETING; FRAGMENT BASED DRUG DISCOVERY; FRAGMENTATION REACTION; HUMAN; LIPOPHILICITY; MEDICINAL CHEMISTRY; MOLECULAR WEIGHT; PROTEIN PROTEIN INTERACTION; PUBLICATION; REVIEW; SCIENTIST; X RAY CRYSTALLOGRAPHY; DRUG DEVELOPMENT; PUBLISHING;

CHEMISTRY, PHARMACEUTICAL; DRUG DISCOVERY; PUBLISHING;

EID: 85018510170     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.6b01123     Document Type: Review

References (55)

1. Davis, B. J.; Erlanson, D. A. Learning from our mistakes: the “unknown knowns” in fragment screening Bioorg. Med. Chem. Lett. 2013, 23 ( 10 ) 2844-2852 10.1016/j.bmcl.2013.03.028
2. Erlanson, D. A. Introduction to fragment-based drug discovery Top. Curr. Chem. 2011, 317, 1-32 10.1007/128_2011_180
3. Erlanson, D. A.; Fesik, S. W.; Hubbard, R. E.; Jahnke, W.; Jhoti, H. Twenty years on: the impact of fragments on drug discovery Nat. Rev. Drug Discovery 2016, 15 ( 9 ) 605-619 10.1038/nrd.2016.109
4. Hubbard, R. E.; Murray, J. B. Experiences in fragment-based lead discovery Methods Enzymol. 2011, 493, 509-531 10.1016/B978-0-12-381274-2.00020-0
5. Magee, T. V. Progress in discovery of small-molecule modulators of protein-protein interactions via fragment screening Bioorg. Med. Chem. Lett. 2015, 25, 2461-2468 10.1016/j.bmcl.2015.04.089
6. Murray, C. W.; Rees, D. C. The rise of fragment-based drug discovery Nat. Chem. 2009, 1, 187-192 10.1038/nchem.217
7. Zartler, E. R. Fragonomics: the-omics with real impact ACS Med. Chem. Lett. 2014, 5 ( 9 ) 952-953 10.1021/ml5003212
8. Baker, M. Fragment-based lead discovery grows up Nat. Rev. Drug Discovery 2013, 12 ( 1 ) 5-7 10.1038/nrd3926
9. Bollag, G.; Tsai, J.; Zhang, J.; Zhang, C.; Ibrahim, P.; Nolop, K.; Hirth, P. Vemurafenib: the first drug approved for BRAF-mutant cancer Nat. Rev. Drug Discovery 2012, 11 ( 11 ) 873-886 10.1038/nrd3847
10. Souers, A. J.; Leverson, J. D.; Boghaert, E. R.; Ackler, S. L.; Catron, N. D.; Chen, J.; Dayton, B. D.; Ding, H.; Enschede, S. H.; Fairbrother, W. J.; Huang, D. C.; Hymowitz, S. G.; Jin, S.; Khaw, S. L.; Kovar, P. J.; Lam, L. T.; Lee, J.; Maecker, H. L.; Marsh, K. C.; Mason, K. D.; Mitten, M. J.; Nimmer, P. M.; Oleksijew, A.; Park, C. H.; Park, C. M.; Phillips, D. C.; Roberts, A. W.; Sampath, D.; Seymour, J. F.; Smith, M. L.; Sullivan, G. M.; Tahir, S. K.; Tse, C.; Wendt, M. D.; Xiao, Y.; Xue, J. C.; Zhang, H.; Humerickhouse, R. A.; Rosenberg, S. H.; Elmore, S. W. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets Nat. Med. 2013, 19 ( 2 ) 202-208 10.1038/nm.3048
11. Alex, A. A.; Flocco, M. M. Fragment-based drug discovery: what has it achieved so far? Curr. Top. Med. Chem. 2007, 7 ( 16 ) 1544-1567 10.2174/156802607782341082
12. Congreve, M.; Murray, C. W.; Carr, R.; Rees, D. C. Fragment-based lead discovery. In Annual Reports in Medicinal Chemistry; John, E. M., Ed.; Academic Press: New York, NY, 2007; Vol. 42, Chapter 28, pp 431-448.
13. de Kloe, G. E.; Bailey, D.; Leurs, R.; de Esch, I. J. Transforming fragments into candidates: small becomes big in medicinal chemistry Drug Discovery Today 2009, 14 ( 13-14 ) 630-646 10.1016/j.drudis.2009.03.009
14. Erlanson, D. A. Fragment-based lead discovery: a chemical update Curr. Opin. Biotechnol. 2006, 17 ( 6 ) 643-652 10.1016/j.copbio.2006.10.007
15. Ferenczy, G. G.; Keseru, G. M. How are fragments optimized? A retrospective analysis of 145 fragment optimizations J. Med. Chem. 2013, 56 ( 6 ) 2478-2486 10.1021/jm301851v
16. Congreve, M.; Carr, R.; Murray, C.; Jhoti, H. A “rule of three” for fragment-based lead discovery? Drug Discovery Today 2003, 8 ( 19 ) 876-877 10.1016/S1359-6446(03)02831-9
17. Jhoti, H.; Williams, G.; Rees, D. C.; Murray, C. W. The “rule of three” for fragment-based drug discovery: where are we now? Nat. Rev. Drug Discovery 2013, 12 ( 8 ) 644-645 10.1038/nrd3926-c1
18. Clark, P. G.; Vieira, L. C.; Tallant, C.; Fedorov, O.; Singleton, D. C.; Rogers, C. M.; Monteiro, O. P.; Bennett, J. M.; Baronio, R.; Muller, S.; Daniels, D. L.; Mendez, J.; Knapp, S.; Brennan, P. E.; Dixon, D. J. LP99: Discovery and synthesis of the first selective BRD7/9 bromodomain inhibitor Angew. Chem., Int. Ed. 2015, 54 ( 21 ) 6217-6221 10.1002/anie.201501394
19. Jamali, H.; Khan, H. A.; Stringer, J. R.; Chowdhury, S.; Ellman, J. A. Identification of multiple structurally distinct, nonpeptidic small molecule inhibitors of protein arginine deiminase 3 using a substrate-based fragment method J. Am. Chem. Soc. 2015, 137 ( 10 ) 3616-3621 10.1021/jacs.5b00095
20. Karpov, A. S.; Amiri, P.; Bellamacina, C.; Bellance, M. H.; Breitenstein, W.; Daniel, D.; Denay, R.; Fabbro, D.; Fernandez, C.; Galuba, I.; Guerro-Lagasse, S.; Gutmann, S.; Hinh, L.; Jahnke, W.; Klopp, J.; Lai, A.; Lindvall, M. K.; Ma, S.; Mobitz, H.; Pecchi, S.; Rummel, G.; Shoemaker, K.; Trappe, J.; Voliva, C.; Cowan-Jacob, S. W.; Marzinzik, A. L. Optimization of a dibenzodiazepine hit to a potent and selective allosteric PAK1 inhibitor ACS Med. Chem. Lett. 2015, 6 ( 7 ) 776-781 10.1021/acsmedchemlett.5b00102
21. Perfetti, M. T.; Baughman, B. M.; Dickson, B. M.; Mu, Y.; Cui, G.; Mader, P.; Dong, A.; Norris, J. L.; Rothbart, S. B.; Strahl, B. D.; Brown, P. J.; Janzen, W. P.; Arrowsmith, C. H.; Mer, G.; McBride, K. M.; James, L. I.; Frye, S. V. Identification of a fragment-like small molecule ligand for the methyl-lysine binding protein, 53BP1 ACS Chem. Biol. 2015, 10 ( 4 ) 1072-1081 10.1021/cb500956g
22. Ranganathan, A.; Stoddart, L. A.; Hill, S. J.; Carlsson, J. Fragment-based discovery of subtype-selective adenosine receptor ligands from homology models J. Med. Chem. 2015, 58 ( 24 ) 9578-9590 10.1021/acs.jmedchem.5b01120
23. Leo, A.; Weininger, D. CLOGP reference manual, Daylight version 4.9. http://www.daylight.com/dayhtml/doc/clogp/.
24. Smith, C. R.; Dougan, D. R.; Komandla, M.; Kanouni, T.; Knight, B.; Lawson, J. D.; Sabat, M.; Taylor, E. R.; Vu, P.; Wyrick, C. Fragment-based discovery of a small molecule inhibitor of Bruton’s tyrosine kinase J. Med. Chem. 2015, 58 ( 14 ) 5437-5444 10.1021/acs.jmedchem.5b00734
25. Murray, C. W.; Berdini, V.; Buck, I. M.; Carr, M. E.; Cleasby, A.; Coyle, J. E.; Curry, J. E.; Day, J. E.; Day, P. J.; Hearn, K.; Iqbal, A.; Lee, L. Y.; Martins, V.; Mortenson, P. N.; Munck, J. M.; Page, L. W.; Patel, S.; Roomans, S.; Smith, K.; Tamanini, E.; Saxty, G. Fragment-based discovery of potent and selective DDR1/2 Inhibitors ACS Med. Chem. Lett. 2015, 6 ( 7 ) 798-803 10.1021/acsmedchemlett.5b00143
26. Burdick, D. J.; Wang, S.; Heise, C.; Pan, B.; Drummond, J.; Yin, J.; Goeser, L.; Magnuson, S.; Blaney, J.; Moffat, J.; Wang, W.; Chen, H. Fragment-based discovery of potent ERK2 pyrrolopyrazine inhibitors Bioorg. Med. Chem. Lett. 2015, 25 ( 21 ) 4728-4732 10.1016/j.bmcl.2015.08.048
27. Johnson, C. N.; Berdini, V.; Beke, L.; Bonnet, P.; Brehmer, D.; Coyle, J. E.; Day, P. J.; Frederickson, M.; Freyne, E. J.; Gilissen, R. A.; Hamlett, C. C.; Howard, S.; Meerpoel, L.; McMenamin, R.; Patel, S.; Rees, D. C.; Sharff, A.; Sommen, F.; Wu, T.; Linders, J. T. Fragment-based discovery of type I inhibitors of maternal embryonic leucine zipper kinase ACS Med. Chem. Lett. 2015, 6 ( 1 ) 25-30 10.1021/ml5001245
28. Johnson, C. N.; Adelinet, C.; Berdini, V.; Beke, L.; Bonnet, P.; Brehmer, D.; Calo, F.; Coyle, J. E.; Day, P. J.; Frederickson, M.; Freyne, E. J.; Gilissen, R. A.; Hamlett, C. C.; Howard, S.; Meerpoel, L.; Mevellec, L.; McMenamin, R.; Pasquier, E.; Patel, S.; Rees, D. C.; Linders, J. T. Structure-based design of type II inhibitors applied to maternal embryonic leucine zipper kinase ACS Med. Chem. Lett. 2015, 6 ( 1 ) 31-36 10.1021/ml5001273
29. Naik, M.; Raichurkar, A.; Bandodkar, B. S.; Varun, B. V.; Bhat, S.; Kalkhambkar, R.; Murugan, K.; Menon, R.; Bhat, J.; Paul, B.; Iyer, H.; Hussein, S.; Tucker, J. A.; Vogtherr, M.; Embrey, K. J.; McMiken, H.; Prasad, S.; Gill, A.; Ugarkar, B. G.; Venkatraman, J.; Read, J.; Panda, M. Structure guided lead generation for M. tuberculosis thymidylate kinase (Mtb TMK): discovery of 3-cyanopyridone and 1,6-naphthyridin-2-one as potent inhibitors J. Med. Chem. 2015, 58 ( 2 ) 753-766 10.1021/jm5012947
30. Hu, H.; Wang, X.; Chan, G. K.; Chang, J. H.; Do, S.; Drummond, J.; Ebens, A.; Lee, W.; Ly, J.; Lyssikatos, J. P.; Murray, J.; Moffat, J. G.; Chao, Q.; Tsui, V.; Wallweber, H.; Kolesnikov, A. Discovery of 3,5-substituted 6-azaindazoles as potent pan-Pim inhibitors Bioorg. Med. Chem. Lett. 2015, 25 ( 22 ) 5258-5264 10.1016/j.bmcl.2015.09.052
31. George, D. M.; Breinlinger, E. C.; Friedman, M.; Zhang, Y.; Wang, J.; Argiriadi, M.; Bansal-Pakala, P.; Barth, M.; Duignan, D. B.; Honore, P.; Lang, Q.; Mittelstadt, S.; Potin, D.; Rundell, L.; Edmunds, J. J. Discovery of selective and orally bioavailable protein kinase Ctheta (PKCtheta) inhibitors from a fragment hit J. Med. Chem. 2015, 58 ( 1 ) 222-236 10.1021/jm500669m
32. Frett, B.; Carlomagno, F.; Moccia, M. L.; Brescia, A.; Federico, G.; De Falco, V.; Admire, B.; Chen, Z.; Qi, W.; Santoro, M.; Li, H. Y. Fragment-based discovery of a dual pan-RET/VEGFR2 kinase inhibitor optimized for single-agent polypharmacology Angew. Chem., Int. Ed. 2015, 54 ( 30 ) 8717-8721 10.1002/anie.201501104
33. Winneroski, L. L.; Schiffler, M. A.; Erickson, J. A.; May, P. C.; Monk, S. A.; Timm, D. E.; Audia, J. E.; Beck, J. P.; Boggs, L. N.; Borders, A. R.; Boyer, R. D.; Brier, R. A.; Hudziak, K. J.; Klimkowski, V. J.; Garcia Losada, P.; Mathes, B. M.; Stout, S. L.; Watson, B. M.; Mergott, D. J. Preparation and biological evaluation of conformationally constrained BACE1 inhibitors Bioorg. Med. Chem. 2015, 23 ( 13 ) 3260-3268 10.1016/j.bmc.2015.04.062
34. Cheney, D. L.; Bozarth, J. M.; Metzler, W. J.; Morin, P. E.; Mueller, L.; Newitt, J. A.; Nirschl, A. H.; Rendina, A. R.; Tamura, J. K.; Wei, A.; Wen, X.; Wurtz, N. R.; Seiffert, D. A.; Wexler, R. R.; Priestley, E. S. Discovery of novel P1 groups for coagulation factor VIIa inhibition using fragment-based screening J. Med. Chem. 2015, 58 ( 6 ) 2799-2808 10.1021/jm501982k
35. Fjellstrom, O.; Akkaya, S.; Beisel, H. G.; Eriksson, P. O.; Erixon, K.; Gustafsson, D.; Jurva, U.; Kang, D.; Karis, D.; Knecht, W.; Nerme, V.; Nilsson, I.; Olsson, T.; Redzic, A.; Roth, R.; Sandmark, J.; Tigerstrom, A.; Oster, L. Creating novel activated factor XI inhibitors through fragment based lead generation and structure aided drug design PLoS One 2015, 10 ( 1 ) e0113705 10.1371/journal.pone.0113705
36. Lanz, J.; Riedl, R. Merging allosteric and active site binding motifs: de novo generation of target selectivity and potency via natural-product-derived fragments ChemMedChem 2015, 10 ( 3 ) 451-454 10.1002/cmdc.201402478
37. Bertrand, S. M.; Ancellin, N.; Beaufils, B.; Bingham, R. P.; Borthwick, J. A.; Boullay, A. B.; Boursier, E.; Carter, P. S.; Chung, C. W.; Churcher, I.; Dodic, N.; Fouchet, M. H.; Fournier, C.; Francis, P. L.; Gummer, L. A.; Herry, K.; Hobbs, A.; Hobbs, C. I.; Homes, P.; Jamieson, C.; Nicodeme, E.; Pickett, S. D.; Reid, I. H.; Simpson, G. L.; Sloan, L. A.; Smith, S. E.; Somers, D. O.; Spitzfaden, C.; Suckling, C. J.; Valko, K.; Washio, Y.; Young, R. J. The discovery of in vivo active mitochondrial branched-chain aminotransferase (BCATm) inhibitors by hybridizing fragment and HTS hits J. Med. Chem. 2015, 58 ( 18 ) 7140-7163 10.1021/acs.jmedchem.5b00313
38. Chen, G.-Y.; Ng, F. M.; Tan, Y. W.; Poulsen, A.; Seetoh, W.; Lin, G.; Kang, C.; Then, S. W.; Ahmad, N. H.; Wong, Y. L.; Ng, H. Q.; Chia, C. S. B.; Lau, Q. Y.; Hill, J.; Hung, A. W.; Keller, T. H. Application of fragment-based drug discovery against DNA gyrase B ChemPlusChem 2015, 80 ( 8 ) 1250-1254 10.1002/cplu.201500197
39. Hale, M. R.; Brassington, C.; Carcanague, D.; Embrey, K.; Eyermann, C. J.; Giacobbe, R. A.; Gingipalli, L.; Gowravaram, M.; Harang, J.; Howard, T.; Ioannidis, G.; Jahic, H.; Kutschke, A.; Laganas, V. A.; Loch, J.; Miller, M. D.; Murphy-Benenato, K. E.; Oguto, H.; Otterbein, L.; Patel, S. J.; Shapiro, A. B.; Boriack-Sjodin, P. A. From fragments to leads: novel bacterial NAD+-dependent DNA ligase inhibitors Tetrahedron Lett. 2015, 56 ( 23 ) 3108-3112 10.1016/j.tetlet.2014.12.067
40. He, R.; Yu, Z. H.; Zhang, R. Y.; Wu, L.; Gunawan, A. M.; Zhang, Z. Y. Cefsulodin inspired potent and selective inhibitors of mPTPB, a virulent phosphatase from mycobacterium tuberculosis ACS Med. Chem. Lett. 2015, 6 ( 12 ) 1231-1235 10.1021/acsmedchemlett.5b00373
41. Shipe, W. D.; Sharik, S. S.; Barrow, J. C.; McGaughey, G. B.; Theberge, C. R.; Uslaner, J. M.; Yan, Y.; Renger, J. J.; Smith, S. M.; Coleman, P. J.; Cox, C. D. Discovery and optimization of a series of pyrimidine-based phosphodiesterase 10A (PDE10A) inhibitors through fragment screening, structure-based design, and parallel synthesis J. Med. Chem. 2015, 58 ( 19 ) 7888-7894 10.1021/acs.jmedchem.5b00983
42. Amano, Y.; Tanabe, E.; Yamaguchi, T. Identification of N-ethylmethylamine as a novel scaffold for inhibitors of soluble epoxide hydrolase by crystallographic fragment screening Bioorg. Med. Chem. 2015, 23 ( 10 ) 2310-2317 10.1016/j.bmc.2015.03.083
43. de Vicente, J.; Tivitmahaisoon, P.; Berry, P.; Bolin, D. R.; Carvajal, D.; He, W.; Huang, K. S.; Janson, C.; Liang, L.; Lukacs, C.; Petersen, A.; Qian, H.; Yi, L.; Zhuang, Y.; Hermann, J. C. Fragment-based drug design of novel pyranopyridones as cell active and orally bioavailable tankyrase inhibitors ACS Med. Chem. Lett. 2015, 6 ( 9 ) 1019-1024 10.1021/acsmedchemlett.5b00251
44. He, Y.; Guo, X.; Yu, Z. H.; Wu, L.; Gunawan, A. M.; Zhang, Y.; Dixon, J. E.; Zhang, Z. Y. A potent and selective inhibitor for the UBLCP1 proteasome phosphatase Bioorg. Med. Chem. 2015, 23 ( 12 ) 2798-2809 10.1016/j.bmc.2015.03.066
45. Bamborough, P.; Chung, C. W.; Furze, R. C.; Grandi, P.; Michon, A. M.; Sheppard, R. J.; Barnett, H.; Diallo, H.; Dixon, D. P.; Douault, C.; Jones, E. J.; Karamshi, B.; Mitchell, D. J.; Prinjha, R. K.; Rau, C.; Watson, R. J.; Werner, T.; Demont, E. H. Structure-based optimization of naphthyridones into potent ATAD2 bromodomain inhibitors J. Med. Chem. 2015, 58 ( 15 ) 6151-6178 10.1021/acs.jmedchem.5b00773
46. Demont, E. H.; Chung, C. W.; Furze, R. C.; Grandi, P.; Michon, A. M.; Wellaway, C.; Barrett, N.; Bridges, A. M.; Craggs, P. D.; Diallo, H.; Dixon, D. P.; Douault, C.; Emmons, A. J.; Jones, E. J.; Karamshi, B. V.; Locke, K.; Mitchell, D. J.; Mouzon, B. H.; Prinjha, R. K.; Roberts, A. D.; Sheppard, R. J.; Watson, R. J.; Bamborough, P. Fragment-based discovery of low-micromolar ATAD2 bromodomain inhibitors J. Med. Chem. 2015, 58 ( 14 ) 5649-5673 10.1021/acs.jmedchem.5b00772
47. Burke, J. P.; Bian, Z.; Shaw, S.; Zhao, B.; Goodwin, C. M.; Belmar, J.; Browning, C. F.; Vigil, D.; Friberg, A.; Camper, D. V.; Rossanese, O. W.; Lee, T.; Olejniczak, E. T.; Fesik, S. W. Discovery of tricyclic indoles that potently inhibit Mcl-1 using fragment-based methods and structure-based design J. Med. Chem. 2015, 58 ( 9 ) 3794-3805 10.1021/jm501984f
48. Scott, D. E.; Coyne, A. G.; Venkitaraman, A.; Blundell, T. L.; Abell, C.; Hyvonen, M. Small-molecule inhibitors that target protein-protein interactions in the RAD51 family of recombinases ChemMedChem 2015, 10 ( 2 ) 296-303 10.1002/cmdc.201402428
49. Waterson, A. G.; Kennedy, J. P.; Patrone, J. D.; Pelz, N. F.; Feldkamp, M. D.; Frank, A. O.; Vangamudi, B.; Souza-Fagundes, E. M.; Rossanese, O. W.; Chazin, W. J.; Fesik, S. W. Diphenylpyrazoles as replication protein a inhibitors ACS Med. Chem. Lett. 2015, 6 ( 2 ) 140-145 10.1021/ml5003629
50. Chessari, G.; Buck, I. M.; Day, J. E.; Day, P. J.; Iqbal, A.; Johnson, C. N.; Lewis, E. J.; Martins, V.; Miller, D.; Reader, M.; Rees, D. C.; Rich, S. J.; Tamanini, E.; Vitorino, M.; Ward, G. A.; Williams, P. A.; Williams, G.; Wilsher, N. E.; Woolford, A. J. Fragment-based drug discovery targeting inhibitor of apoptosis proteins: discovery of a non-alanine lead series with dual activity against cIAP1 and XIAP J. Med. Chem. 2015, 58 ( 16 ) 6574-6588 10.1021/acs.jmedchem.5b00706
51. Christopher, J. A.; Aves, S. J.; Bennett, K. A.; Dore, A. S.; Errey, J. C.; Jazayeri, A.; Marshall, F. H.; Okrasa, K.; Serrano-Vega, M. J.; Tehan, B. G.; Wiggin, G. R.; Congreve, M. Fragment and structure-based drug discovery for a class C GPCR: discovery of the mGlu5 negative allosteric modulator HTL14242 (3-Chloro-5-[6-(5-fluoropyridin-2-yl)pyrimidin-4-yl]benzonitrile) J. Med. Chem. 2015, 58 ( 16 ) 6653-6664 10.1021/acs.jmedchem.5b00892
52. Hopkins, A. L.; Groom, C. R.; Alex, A. Ligand efficiency: a useful metric for lead selection Drug Discovery Today 2004, 9 ( 10 ) 430-431 10.1016/S1359-6446(04)03069-7
53. Leeson, P. D.; Springthorpe, B. The influence of drug-like concepts on decision-making in medicinal chemistry Nat. Rev. Drug Discovery 2007, 6 ( 11 ) 881-890 10.1038/nrd2445
54. Ryckmans, T.; Edwards, M. P.; Horne, V. A.; Correia, A. M.; Owen, D. R.; Thompson, L. R.; Tran, I.; Tutt, M. F.; Young, T. Rapid assessment of a novel series of selective CB(2) agonists using parallel synthesis protocols: a lipophilic efficiency (LipE) analysis Bioorg. Med. Chem. Lett. 2009, 19 ( 15 ) 4406-4409 10.1016/j.bmcl.2009.05.062
55. Mortenson, P. N.; Murray, C. W. Assessing the lipophilicity of fragments and early hits J. Comput.-Aided Mol. Des. 2011, 25 ( 7 ) 663-667 10.1007/s10822-011-9435-z