Aryl Sulfonamide Inhibitors of Insulin-Regulated Aminopeptidase Enhance Spine Density in Primary Hippocampal Neuron Cultures

ACS Chemical Neuroscience

Volumn 7, Issue 10, 2016, Pages 1383-1392

  Diwakarla, Shanti ^a   Nylander, Erik ^a   Grönbladh, Alfhild ^a   Vanga, Sudarsana Reddy ^a   Khan, Yasmin Shamsudin ^a   Gutiérrez De Terán, Hugo ^a   Sävmarker, Jonas ^a   Ng, Leelee ^d   Pham, Vi ^d   Lundbäck, Thomas ^c   Jenmalm Jensen, Annika ^c   Svensson, Richard ^a   Artursson, Per ^a   Zelleroth, Sofia ^a   Engen, Karin ^a   Rosenström, Ulrika ^a   Larhed, Mats ^b   Åqvist, Johan ^a   Chai, Siew Yeen ^d   Hallberg, Mathias ^a  

^a UPPSALA UNIVERSITY   (Sweden)

^b UPPSALA UNIVERSITY   (Sweden)

^c KAROLINSKA INSTITUTE   (Sweden)

^d MONASH UNIVERSITY   (Australia)

Author keywords

aryl sulfonamides; dendritic spines; hippocampal neurons; Insulin regulated aminopeptidase; ligand interaction energy simulations; molecular dynamics

Indexed keywords

AMINOPEPTIDASE INHIBITOR; LEUKOTRIENE A4 HYDROLASE; MICROSOMAL AMINOPEPTIDASE; SULFONAMIDE; CYSTYL AMINOPEPTIDASE; ENZYME INHIBITOR; EPOXIDE HYDROLASE; LEUCYL-CYSTINYL AMINOPEPTIDASE; PROTEIN BINDING; RECOMBINANT PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; CELL MEMBRANE PERMEABILITY; CELL VIABILITY; COGNITION; DENDRITIC SPINE; DRUG SELECTIVITY; DRUG SOLUBILITY; DRUG STRUCTURE; ENZYME INHIBITION; HIPPOCAMPAL NEURONAL CULTURE; HUMAN; HUMAN TISSUE; IC50; IMMUNOCYTOCHEMISTRY; KINETICS; METABOLIC STABILITY; MOLECULAR DOCKING; MOLECULAR DYNAMICS; MOUSE; NONHUMAN; PRIORITY JOURNAL; RAT; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL CULTURE; CHEMICAL STRUCTURE; COCULTURE; CYTOLOGY; DRUG EFFECTS; ENZYMOLOGY; GENETICS; HEK293 CELL LINE; HIPPOCAMPUS; METABOLISM; PRECLINICAL STUDY; SPRAGUE DAWLEY RAT; SYNTHESIS;

ANIMALS; ANTIGENS, CD13; CELLS, CULTURED; COCULTURE TECHNIQUES; CYSTINYL AMINOPEPTIDASE; DENDRITIC SPINES; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; EPOXIDE HYDROLASES; HEK293 CELLS; HIPPOCAMPUS; HUMANS; MOLECULAR DOCKING SIMULATION; MOLECULAR DYNAMICS SIMULATION; MOLECULAR STRUCTURE; PROTEIN BINDING; RATS, SPRAGUE-DAWLEY; RECOMBINANT PROTEINS; SULFONAMIDES;

EID: 84992186834     PISSN: None     EISSN: 19487193     Source Type: Journal    
DOI: 10.1021/acschemneuro.6b00146     Document Type: Article

References (71)

1. Albiston, A. L., McDowall, S. G., Matsacos, D., Sim, P., Clune, E., Mustafa, T., Lee, J., Mendelsohn, F. A., Simpson, R. J., Connolly, L. M., and Chai, S. Y. (2001) Evidence that the angiotensin IV (AT(4)) receptor is the enzyme insulin- regulated aminopeptidase J. Biol. Chem. 276, 48623-48626 10.1074/jbc.C100512200
2. Lew, R. A., Mustafa, T., Ye, S., McDowall, S. G., Chai, S. Y., and Albiston, A. L. (2003) Angiotensin AT4 ligands are potent, competitive inhibitors of insulin regulated aminopeptidase (IRAP) J. Neurochem. 86, 344-350 10.1046/j.1471-4159.2003.01852.x
3. Harding, J. W., Cook, V. I., Miller-Wing, A. V., Hanesworth, J. M., Sardinia, M. F., Hall, K. L., Stobb, J. W., Swanson, G. N., Coleman, J. K., Wright, J. W., and Harding, E. C. (1992) Identification of an AII(3-8) [AIV] binding site in guinea pig hippocampus Brain Res. 583, 340-343 10.1016/S0006-8993(10)80047-2
4. Roberts, K. A., Krebs, L. T., Kramar, E. A., Shaffer, M. J., Harding, J. W., and Wright, J. W. (1995) Autoradiographic identification of brain angiotensin IV binding sites and differential c-Fos expression following intracerebroventricular injection of angiotensin II and IV in rats Brain Res. 682, 13-21 10.1016/0006-8993(95)00289-3
5. Chai, S. Y., Bastias, M. A., Clune, E. F., Matsacos, D. J., Mustafa, T., Lee, J. H., McDowall, S. G., Paxinos, G., Mendelsohn, F. A., and Albiston, A. L. (2000) Distribution of angiotensin IV binding sites (AT4 receptor) in the human forebrain, midbrain and pons as visualised by in vitro receptor autoradiography J. Chem. Neuroanat. 20, 339-348 10.1016/S0891-0618(00)00112-5
6. Braszko, J. J., Kupryszewski, G., Witczuk, B., and Wisniewski, K. (1988) Angiotensin II-(3-8)-hexapeptide affects motor activity, performance of passive avoidance and a conditioned avoidance response in rats Neuroscience 27, 777-783 10.1016/0306-4522(88)90182-0
7. De Bundel, D., Smolders, I., Yang, R., Albiston, A. L., Michotte, Y., and Chai, S. Y. (2009) Angiotensin IV and LVV-haemorphin 7 enhance spatial working memory in rats: effects on hippocampal glucose levels and blood flow Neurobiol. Learn. Mem. 92, 19-26 10.1016/j.nlm.2009.02.004
8. Gard, P. R., Naylor, C., Ali, S., and Partington, C. (2012) Blockade of pro-cognitive effects of angiotensin IV and physostigmine in mice by oxytocin antagonism Eur. J. Pharmacol. 683, 155-160 10.1016/j.ejphar.2012.02.048
9. Wright, J. W., Stubley, L., Pederson, E. S., Kramar, E. A., Hanesworth, J. M., and Harding, J. W. (1999) Contributions of the brain angiotensin IV-AT4 receptor subtype system to spatial learning J. Neurosci. 19, 3952-3961
10. Albiston, A. L., Morton, C. J., Ng, H. L., Pham, V., Yeatman, H. R., Ye, S., Fernando, R. N., De Bundel, D., Ascher, D. B., Mendelsohn, F. A., Parker, M. W., and Chai, S. Y. (2008) Identification and characterization of a new cognitive enhancer based on inhibition of insulin-regulated aminopeptidase FASEB J. 22, 4209-4217 10.1096/fj.08-112227
11. Mountford, S. J., Albiston, A. L., Charman, W. N., Ng, L., Holien, J. K., Parker, M. W., Nicolazzo, J. A., Thompson, P. E., and Chai, S. Y. (2014) Synthesis, structure-activity relationships and brain uptake of a novel series of benzopyran inhibitors of insulin-regulated aminopeptidase J. Med. Chem. 57, 1368-1377 10.1021/jm401540f
12. Albiston, A. L., Diwakarla, S., Fernando, R. N., Mountford, S. J., Yeatman, H. R., Morgan, B., Pham, V., Holien, J. K., Parker, M. W., Thompson, P. E., and Chai, S. Y. (2011) Identification and development of specific inhibitors for insulin-regulated aminopeptidase as a new class of cognitive enhancers Br. J. Pharmacol. 164, 37-47 10.1111/j.1476-5381.2011.01402.x
13. Benoist, C. C., Wright, J. W., Zhu, M., Appleyard, S. M., Wayman, G. A., and Harding, J. W. (2011) Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogs J. Pharmacol. Exp. Ther. 339, 35-44 10.1124/jpet.111.182220
14. McCoy, A. T., Benoist, C. C., Wright, J. W., Kawas, L. H., Bule-Ghogare, J. M., Zhu, M., Appleyard, S. M., Wayman, G. A., and Harding, J. W. (2013) Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents J. Pharmacol. Exp. Ther. 344, 141-154 10.1124/jpet.112.199497
15. Bourne, J. N. and Harris, K. M. (2008) Balancing structure and function at hippocampal dendritic spines Annu. Rev. Neurosci. 31, 47-67 10.1146/annurev.neuro.31.060407.125646
16. Korobova, F. and Svitkina, T. (2010) Molecular architecture of synaptic actin cytoskeleton in hippocampal neurons reveals a mechanism of dendritic spine morphogenesis Mol. Biol. Cell 21, 165-176 10.1091/mbc.E09-07-0596
17. Axen, A., Andersson, H., Lindeberg, G., Ronnholm, H., Kortesmaa, J., Demaegdt, H., Vauquelin, G., Karlen, A., and Hallberg, M. (2007) Small potent ligands to the insulin-regulated aminopeptidase (IRAP)/AT(4) receptor J. Pept. Sci. 13, 434-444 10.1002/psc.859
18. Axen, A., Lindeberg, G., Demaegdt, H., Vauquelin, G., Karlen, A., and Hallberg, M. (2006) Cyclic insulin-regulated aminopeptidase (IRAP)/AT4 receptor ligands J. Pept. Sci. 12, 705-713 10.1002/psc.782
19. Andersson, H., Demaegdt, H., Johnsson, A., Vauquelin, G., Lindeberg, G., Hallberg, M., Erdelyi, M., Karlen, A., and Hallberg, A. (2011) Potent macrocyclic inhibitors of insulin-regulated aminopeptidase (IRAP) by olefin ring-closing metathesis J. Med. Chem. 54, 3779-3792 10.1021/jm200036n
20. Andersson, H., Demaegdt, H., Vauquelin, G., Lindeberg, G., Karlen, A., and Hallberg, M. (2008) Ligands to the (IRAP)/AT4 receptor encompassing a 4-hydroxydiphenylmethane scaffold replacing Tyr2 Bioorg. Med. Chem. 16, 6924-6935 10.1016/j.bmc.2008.05.046
21. Andersson, H., Demaegdt, H., Vauquelin, G., Lindeberg, G., Karlen, A., Hallberg, M., Erdelyi, M., and Hallberg, A. (2010) Disulfide cyclized tripeptide analogues of angiotensin IV as potent and selective inhibitors of insulin-regulated aminopeptidase (IRAP) J. Med. Chem. 53, 8059-8071 10.1021/jm100793t
22. Hallberg, M. (2009) Targeting the insulin-regulated aminopeptidase/AT4 receptor for cognitive disorders Drug News Perspect. 22, 133-139 10.1358/dnp.2009.22.3.1325032
23. Stragier, B., De Bundel, D., Sarre, S., Smolders, I., Vauquelin, G., Dupont, A., Michotte, Y., and Vanderheyden, P. (2008) Involvement of insulin-regulated aminopeptidase in the effects of the renin-angiotensin fragment angiotensin IV: a review Heart Failure Rev. 13, 321-337 10.1007/s10741-007-9062-x
24. Chai, S. Y., Fernando, R., Peck, G., Ye, S. Y., Mendelsohn, F. A., Jenkins, T. A., and Albiston, A. L. (2004) The angiotensin IV/AT4 receptor Cell. Mol. Life Sci. 61, 2728-2737 10.1007/s00018-004-4246-1
25. Diwakarla, S., Nylander, E., Gronbladh, A., Vanga, S. R., Khan, Y. S., Gutierrez-de-Teran, H., Ng, L., Pham, V., Savmarker, J., Lundback, T., Jenmalm-Jensen, A., Andersson, H., Engen, K., Rosenstrom, U., Larhed, M., Aqvist, J., Chai, S. Y., and Hallberg, M. (2016) Binding to and Inhibition of Insulin-Regulated Aminopeptidase by Macrocyclic Disulfides Enhances Spine Density Mol. Pharmacol. 89, 413-424 10.1124/mol.115.102533
26. Benoist, C. C., Kawas, L. H., Zhu, M., Tyson, K. A., Stillmaker, L., Appleyard, S. M., Wright, J. W., Wayman, G. A., and Harding, J. W. (2014) The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system J. Pharmacol. Exp. Ther. 351, 390-402 10.1124/jpet.114.218735
27. Engen, K., Rosenstrom, U., Axelsson, H., Konda, V., Dahllund, L., Otrocka, M., Sigmundsson, K., Nikolaou, A., Vauquelin, G., Hallberg, M., Jenmalm Jensen, A., Lundback, T., and Larhed, M. (2016) Identification of Drug-Like Inhibitors of Insulin-Regulated Aminopeptidase Through Small-Molecule Screening Assay Drug Dev. Technol. 14, 180-193 10.1089/adt.2016.708
28. Borhade, S. R., Rosenstrom, U., Savmarker, J., Lundback, T., Jenmalm-Jensen, A., Sigmundsson, K., Axelsson, H., Svensson, F., Konda, V., Skold, C., Larhed, M., and Hallberg, M. (2014) Inhibition of Insulin-Regulated Aminopeptidase (IRAP) by Arylsulfonamides ChemistryOpen 3, 256-263 10.1002/open.201402027
29. Aqvist, J., Medina, C., and Samuelsson, J. E. (1994) A new method for predicting binding affinity in computer-aided drug design Protein Eng., Des. Sel. 7, 385-391 10.1093/protein/7.3.385
30. Halgren, T. A., Murphy, R. B., Friesner, R. A., Beard, H. S., Frye, L. L., Pollard, W. T., and Banks, J. L. (2004) Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening J. Med. Chem. 47, 1750-1759 10.1021/jm030644s
31. Verdonk, M. L., Cole, J. C., Hartshorn, M. J., Murray, C. W., and Taylor, R. D. (2003) Improved protein-ligand docking using GOLD Proteins: Struct., Funct., Genet. 52, 609-623 10.1002/prot.10465
32. Mpakali, A., Saridakis, E., Harlos, K., Zhao, Y., Papakyriakou, A., Kokkala, P., Georgiadis, D., and Stratikos, E. (2015) Crystal Structure of Insulin-Regulated Aminopeptidase with Bound Substrate Analogue Provides Insight on Antigenic Epitope Precursor Recognition and Processing J. Immunol. 195, 2842-2851 10.4049/jimmunol.1501103
33. Lockett, M. R., Lange, H., Breiten, B., Heroux, A., Sherman, W., Rappoport, D., Yau, P. O., Snyder, P. W., and Whitesides, G. M. (2013) The binding of benzoarylsulfonamide ligands to human carbonic anhydrase is insensitive to formal fluorination of the ligand Angew. Chem., Int. Ed. 52, 7714-7717 10.1002/anie.201301813
34. Moeker, J., Mahon, B. P., Bornaghi, L. F., Vullo, D., Supuran, C. T., McKenna, R., and Poulsen, S. A. (2014) Structural insights into carbonic anhydrase IX isoform specificity of carbohydrate-based sulfamates J. Med. Chem. 57, 8635-8645 10.1021/jm5012935
35. Hermans, S. J., Ascher, D. B., Hancock, N. C., Holien, J. K., Michell, B. J., Chai, S. Y., Morton, C. J., and Parker, M. W. (2015) Crystal structure of human insulin-regulated aminopeptidase with specificity for cyclic peptides Protein Sci. 24, 190-199 10.1002/pro.2604
36. Mahmmoud, R. R., Sase, S., Aher, Y. D., Sase, A., Groger, M., Mokhtar, M., Hoger, H., and Lubec, G. (2015) Spatial and Working Memory Is Linked to Spine Density and Mushroom Spines PLoS One 10, e0139739 10.1371/journal.pone.0139739
37. Hao, J., Rapp, P. R., Leffler, A. E., Leffler, S. R., Janssen, W. G., Lou, W., McKay, H., Roberts, J. A., Wearne, S. L., Hof, P. R., and Morrison, J. H. (2006) Estrogen alters spine number and morphology in prefrontal cortex of aged female rhesus monkeys J. Neurosci. 26, 2571-2578 10.1523/JNEUROSCI.3440-05.2006
38. Leuner, B., Falduto, J., and Shors, T. J. (2003) Associative memory formation increases the observation of dendritic spines in the hippocampus J. Neurosci. 23, 659-665
39. Saneyoshi, T., Fortin, D. A., and Soderling, T. R. (2010) Regulation of spine and synapse formation by activity-dependent intracellular signaling pathways Curr. Opin. Neurobiol. 20, 108-115 10.1016/j.conb.2009.09.013
40. Chapleau, C. A., Carlo, M. E., Larimore, J. L., and Pozzo-Miller, L. (2008) The actions of BDNF on dendritic spine density and morphology in organotypic slice cultures depend on the presence of serum in culture media J. Neurosci. Methods 169, 182-190 10.1016/j.jneumeth.2007.12.006
41. Gu, J., Firestein, B. L., and Zheng, J. Q. (2008) Microtubules in dendritic spine development J. Neurosci. 28, 12120-12124 10.1523/JNEUROSCI.2509-08.2008
42. Dailey, M. E. and Smith, S. J. (1996) The dynamics of dendritic structure in developing hippocampal slices J. Neurosci. 16, 2983-2994
43. Fiala, J. C., Feinberg, M., Popov, V., and Harris, K. M. (1998) Synaptogenesis via dendritic filopodia in developing hippocampal area CA1 J. Neurosci. 18, 8900-8911
44. Papa, M., Bundman, M. C., Greenberger, V., and Segal, M. (1995) Morphological analysis of dendritic spine development in primary cultures of hippocampal neurons J. Neurosci. 15, 1-11
45. Ziv, N. E. and Smith, S. J. (1996) Evidence for a role of dendritic filopodia in synaptogenesis and spine formation Neuron 17, 91-102 10.1016/S0896-6273(00)80283-4
46. Mauch, D. H., Nagler, K., Schumacher, S., Goritz, C., Muller, E. C., Otto, A., and Pfrieger, F. W. (2001) CNS synaptogenesis promoted by glia-derived cholesterol Science 294, 1354-1357 10.1126/science.294.5545.1354
47. Christopherson, K. S., Ullian, E. M., Stokes, C. C., Mullowney, C. E., Hell, J. W., Agah, A., Lawler, J., Mosher, D. F., Bornstein, P., and Barres, B. A. (2005) Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis Cell 120, 421-433 10.1016/j.cell.2004.12.020
48. Beattie, E. C., Stellwagen, D., Morishita, W., Bresnahan, J. C., Ha, B. K., Von Zastrow, M., Beattie, M. S., and Malenka, R. C. (2002) Control of synaptic strength by glial TNFalpha Science 295, 2282-2285 10.1126/science.1067859
49. Kasai, H., Matsuzaki, M., Noguchi, J., Yasumatsu, N., and Nakahara, H. (2003) Structure-stability-function relationships of dendritic spines Trends Neurosci. 26, 360-368 10.1016/S0166-2236(03)00162-0
50. Gong, N., Li, Y., Cai, G. Q., Niu, R. F., Fang, Q., Wu, K., Chen, Z., Lin, L. N., Xu, L., Fei, J., and Xu, T. L. (2009) GABA transporter-1 activity modulates hippocampal theta oscillation and theta burst stimulation-induced long-term potentiation J. Neurosci. 29, 15836-15845 10.1523/JNEUROSCI.4643-09.2009
51. Jerusalinsky, D., Kornisiuk, E., and Izquierdo, I. (1997) Cholinergic neurotransmission and synaptic plasticity concerning memory processing Neurochem. Res. 22, 507-515 10.1023/A:1027376230898
52. Simoff, I., Karlgren, M., Backlund, M., Lindstrom, A. C., Gaugaz, F. Z., Matsson, P., and Artursson, P. (2016) Complete Knockout of Endogenous Mdr1 (Abcb1) in MDCK Cells by CRISPR-Cas9 J. Pharm. Sci. 105, 1017-1021 10.1016/S0022-3549(15)00171-9
53. Hayes, J. D., Flanagan, J. U., and Jowsey, I. R. (2005) Glutathione transferases Annu. Rev. Pharmacol. Toxicol. 45, 51-88 10.1146/annurev.pharmtox.45.120403.095857
54. Isokawa, M., Shimosawa, T., Funatsu, T., and Tsunoda, M. (2016) Determination and characterization of total thiols in mouse serum samples using hydrophilic interaction liquid chromatography with fluorescence detection and mass spectrometry J. Chromatogr. B: Anal. Technol. Biomed. Life Sci. 1019, 59 10.1016/j.jchromb.2015.11.038
55. Gautam, N., Thakare, R., Rana, S., Natarajan, A., and Alnouti, Y. (2015) Irreversible binding of an anticancer compound (BI-94) to plasma proteins Xenobiotica 45, 858-873 10.3109/00498254.2015.1025250
56. Shamsudin Khan, Y., Gutierrez-de-Teran, H., Boukharta, L., and Aqvist, J. (2014) Toward an optimal docking and free energy calculation scheme in ligand design with application to COX-1 inhibitors J. Chem. Inf. Model. 54, 1488-1499 10.1021/ci500151f
57. Marelius, J., Kolmodin, K., Feierberg, I., and Aqvist, J. (1998) Q: a molecular dynamics program for free energy calculations and empirical valence bond simulations in biomolecular systems J. Mol. Graphics Modell. 16, 213-225 10.1016/S1093-3263(98)80006-5
58. Jorgensen, W. L., Maxwell, D. S., and Tirado-Rives, J. (1996) Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids J. Am. Chem. Soc. 118, 11225-11236 10.1021/ja9621760
59. Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W., and Klein, M. L. (1983) Comparison of simple potential functions for simulating liquid water J. Chem. Phys. 79, 926-935 10.1063/1.445869
60. King, G. and Warshel, A. (1989) A surface constrained all-atom solvent model for effective simulations of polar solutions J. Chem. Phys. 91, 3647-3661 10.1063/1.456845
61. Lee, F. S. and Warshel, A. (1992) A local reaction field method for fast evaluation of long-range electrostatic interactions in molecular simulations J. Chem. Phys. 97, 3100-3107 10.1063/1.462997
62. Ryckaert, J.-P., Ciccotti, G., and Berendsen, H. J. C. (1977) Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes J. Comput. Phys. 23, 327-341 10.1016/0021-9991(77)90098-5
63. Boukharta, L., Gutierrez-de-Teran, H., and Aqvist, J. (2014) Computational prediction of alanine scanning and ligand binding energetics in G-protein coupled receptors PLoS Comput. Biol. 10, e1003585 10.1371/journal.pcbi.1003585
64. Shamsudin Khan, Y., Kazemi, M., Gutierrez-de-Teran, H., and Aqvist, J. (2015) Origin of the Enigmatic Stepwise Tight-Binding Inhibition of Cyclooxygenase-1 Biochemistry 54, 7283-7291 10.1021/acs.biochem.5b01024
65. Hansson, T., Marelius, J., and Aqvist, J. (1998) Ligand binding affinity prediction by linear interaction energy methods J. Comput.-Aided Mol. Des. 12, 27-35 10.1023/A:1007930623000
66. Almlof, M., Brandsdal, B. O., and Aqvist, J. (2004) Binding affinity prediction with different force fields: examination of the linear interaction energy method J. Comput. Chem. 25, 1242-1254 10.1002/jcc.20047
67. Almlöf, M., Carlsson, J., and Åqvist, J. (2007) Improving the Accuracy of the Linear Interaction Energy Method for Solvation Free Energies J. Chem. Theory Comput. 3, 2162-2175 10.1021/ct700106b
68. Mishra, S. K., Sund, J., Aqvist, J., and Koca, J. (2012) Computational prediction of monosaccharide binding free energies to lectins with linear interaction energy models J. Comput. Chem. 33, 2340-2350 10.1002/jcc.23081
69. Cheng, Y. and Prusoff, W. H. (1973) Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50% inhibition (I50) of an enzymatic reaction Biochem. Pharmacol. 22, 3099-3108 10.1016/0006-2952(73)90196-2
70. Caraballo, R., Larsson, M., Nilsson, S. K., Ericsson, M., Qian, W., Nguyen Tran, N. P., Kindahl, T., Svensson, R., Saar, V., Artursson, P., Olivecrona, G., Enquist, P. A., and Elofsson, M. (2015) Structure-activity relationships for lipoprotein lipase agonists that lower plasma triglycerides in vivo Eur. J. Med. Chem. 103, 191-209 10.1016/j.ejmech.2015.08.058
71. Hubatsch, I., Ragnarsson, E. G., and Artursson, P. (2007) Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers Nat. Protoc. 2, 2111-2119 10.1038/nprot.2007.303