Structure Activity Relationship and Target Relationship Analysis Based of Formal Concept
Many Approved Drugs Have Bioactive Analogs with Different Target Annotations
Ye Hu, Eugen Lounkine#, and Jürgen Bajorath*
Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität Bonn, Dahlmannstr. 2, D-53113 Bonn, Germany.
#Present address: Novartis Institutes for Biomedical Research, Lead Discovery Informatics, 250 Massachusetts Ave. Cambridge, MA 02139, USA.
Supplementary Table S1
1
Table S1. Drug hubs with potential targets.
DrugID / Name / #Targets(DrugBank) / #Targets
(ChEMBL) / #MMPs / # Potential targets / Potential targets
(ChEMBLID) / Potential targets
(Name) / #Corr. MMPs
DB00194 / Vidarabine / 5 / 1 / 110 / 18 / CHEMBL226 / Adenosine A1 receptor / 19
CHEMBL251 / Adenosine A2a receptor / 23
CHEMBL255 / Adenosine A2b receptor / 7
CHEMBL256 / Adenosine A3 receptor / 35
CHEMBL3589 / Adenosine kinase / 2
CHEMBL2664 / Adenosylhomocysteinase / 27
CHEMBL1993 / DNA (cytosine-5)-methyltransferase 1 / 8
CHEMBL6095 / DNA (cytosine-5)-methyltransferase 3B / 8
CHEMBL1997 / Equilibrative nucleoside transporter 1 / 17
CHEMBL1275223 / Heat shock cognate 71 kDa protein / 1
CHEMBL5523 / Histone-lysine N-methyltransferase SETD7 / 1
CHEMBL1795117 / Histone-lysine N-methyltransferase, H3 lysine-79 specific / 3
CHEMBL4777 / Neuropeptide Y receptor type 1 / 1
CHEMBL4018 / Neuropeptide Y receptor type 2 / 1
CHEMBL5524 / Protein-arginine N-methyltransferase 1 / 1
CHEMBL1824 / Receptor protein-tyrosine kinase erbB-2 / 1
CHEMBL4181 / S-adenosylmethionine decarboxylase 1 / 8
CHEMBL1628469 / Transient receptor potential cation channel subfamily M member 4 / 2
DB00640 / Adenosine / 6 / 2 / 110 / 13 / CHEMBL2664 / Adenosylhomocysteinase / 27
CHEMBL1993 / DNA (cytosine-5)-methyltransferase 1 / 8
CHEMBL6095 / DNA (cytosine-5)-methyltransferase 3B / 8
CHEMBL1997 / Equilibrative nucleoside transporter 1 / 17
CHEMBL1275223 / Heat shock cognate 71 kDa protein / 1
CHEMBL5523 / Histone-lysine N-methyltransferase SETD7 / 1
CHEMBL1795117 / Histone-lysine N-methyltransferase, H3 lysine-79 specific / 3
CHEMBL4777 / Neuropeptide Y receptor type 1 / 1
CHEMBL4018 / Neuropeptide Y receptor type 2 / 1
CHEMBL5524 / Protein-arginine N-methyltransferase 1 / 1
CHEMBL1824 / Receptor protein-tyrosine kinase erbB-2 / 1
CHEMBL4181 / S-adenosylmethionine decarboxylase 1 / 8
CHEMBL1628469 / Transient receptor potential cation channel subfamily M member 4 / 2
DB06155 / Rimonabant / 2 / 4 / 96 / 3 / CHEMBL253 / Cannabinoid CB2 receptor / 39
CHEMBL240 / HERG / 3
CHEMBL2014 / Nociceptin receptor / 6
DB00259 / Sulfanilamide / 6 / 12 / 46 / 17 / CHEMBL261 / Carbonic anhydrase I / 24
CHEMBL205 / Carbonic anhydrase II / 41
CHEMBL2885 / Carbonic anhydrase III / 8
CHEMBL3729 / Carbonic anhydrase IV / 10
CHEMBL3594 / Carbonic anhydrase IX / 20
CHEMBL4789 / Carbonic anhydrase VA / 15
CHEMBL3969 / Carbonic anhydrase VB / 12
CHEMBL3025 / Carbonic anhydrase VI / 12
CHEMBL2326 / Carbonic anhydrase VII / 11
CHEMBL3242 / Carbonic anhydrase XII / 27
CHEMBL3510 / Carbonic anhydrase XIV / 10
CHEMBL202 / Dihydrofolate reductase / 1
CHEMBL2439 / Myeloperoxidase / 1
CHEMBL4282 / Serine/threonine-protein kinase AKT / 1
CHEMBL204 / Thrombin / 1
CHEMBL209 / Trypsin I / 1
CHEMBL4551 / Trypsin III / 1
DB00420 / Promazine / 18 / 23 / 35 / 35 / CHEMBL220 / Acetylcholinesterase / 8
CHEMBL256 / Adenosine A3 receptor / 1
CHEMBL3257 / Aldehyde oxidase / 1
CHEMBL1867 / Alpha-2a adrenergic receptor / 3
CHEMBL1942 / Alpha-2b adrenergic receptor / 3
CHEMBL1916 / Alpha-2c adrenergic receptor / 2
CHEMBL6152 / Alpha-synuclein / 2
CHEMBL6020 / Bile salt export pump / 1
CHEMBL1914 / Butyrylcholinesterase / 27
CHEMBL218 / Cannabinoid CB1 receptor / 1
CHEMBL221 / Cyclooxygenase-1 / 1
CHEMBL230 / Cyclooxygenase-2 / 1
CHEMBL236 / Delta opioid receptor / 1
CHEMBL234 / Dopamine D3 receptor / 3
CHEMBL1850 / Dopamine D5 receptor / 1
CHEMBL238 / Dopamine transporter / 2
CHEMBL203 / Epidermal growth factor receptor erbB1 / 1
CHEMBL240 / HERG / 1
CHEMBL1941 / Histamine H2 receptor / 2
CHEMBL237 / Kappa opioid receptor / 1
CHEMBL4644 / Melanocortin receptor 3 / 1
CHEMBL259 / Melanocortin receptor 4 / 1
CHEMBL4608 / Melanocortin receptor 5 / 1
CHEMBL1951 / Monoamine oxidase A / 1
CHEMBL233 / Mu opioid receptor / 1
CHEMBL1287628 / NADPH oxidase 1 / 3
CHEMBL2327 / Neurokinin 2 receptor / 1
CHEMBL222 / Norepinephrine transporter / 4
CHEMBL1824 / Receptor protein-tyrosine kinase erbB-2 / 1
CHEMBL1833 / Serotonin 2b (5-HT2b) receptor / 3
CHEMBL3371 / Serotonin 6 (5-HT6) receptor / 3
CHEMBL228 / Serotonin transporter / 2
CHEMBL287 / Sigma opioid receptor / 3
CHEMBL5685 / Solute carrier family 22 member 1 / 2
CHEMBL1841 / Tyrosine-protein kinase FYN / 1
DB01246 / Trimeprazine / 2 / NA / 35 / 33 / CHEMBL220 / Acetylcholinesterase / 8
CHEMBL256 / Adenosine A3 receptor / 1
CHEMBL223 / Alpha-1d adrenergic receptor / 3
CHEMBL1867 / Alpha-2a adrenergic receptor / 3
CHEMBL1942 / Alpha-2b adrenergic receptor / 3
CHEMBL1916 / Alpha-2c adrenergic receptor / 2
CHEMBL6152 / Alpha-synuclein / 2
CHEMBL1914 / Butyrylcholinesterase / 27
CHEMBL218 / Cannabinoid CB1 receptor / 1
CHEMBL221 / Cyclooxygenase-1 / 1
CHEMBL230 / Cyclooxygenase-2 / 1
CHEMBL3356 / Cytochrome P450 1A2 / 1
CHEMBL289 / Cytochrome P450 2D6 / 1
CHEMBL2056 / Dopamine D1 receptor / 2
CHEMBL217 / Dopamine D2 receptor / 2
CHEMBL234 / Dopamine D3 receptor / 3
CHEMBL238 / Dopamine transporter / 1
CHEMBL1941 / Histamine H2 receptor / 2
CHEMBL1951 / Monoamine oxidase A / 1
CHEMBL216 / Muscarinic acetylcholine receptor M1 / 3
CHEMBL211 / Muscarinic acetylcholine receptor M2 / 3
CHEMBL245 / Muscarinic acetylcholine receptor M3 / 3
CHEMBL1821 / Muscarinic acetylcholine receptor M4 / 3
CHEMBL2035 / Muscarinic acetylcholine receptor M5 / 3
CHEMBL1287628 / NADPH oxidase 1 / 3
CHEMBL222 / Norepinephrine transporter / 4
CHEMBL224 / Serotonin 2a (5-HT2a) receptor / 3
CHEMBL1833 / Serotonin 2b (5-HT2b) receptor / 3
CHEMBL225 / Serotonin 2c (5-HT2c) receptor / 4
CHEMBL3371 / Serotonin 6 (5-HT6) receptor / 3
CHEMBL228 / Serotonin transporter / 2
CHEMBL287 / Sigma opioid receptor / 3
CHEMBL5685 / Solute carrier family 22 member 1 / 2
DB01069 / Promethazine / 14 / 22 / 34 / 25 / CHEMBL220 / Acetylcholinesterase / 8
CHEMBL256 / Adenosine A3 receptor / 1
CHEMBL223 / Alpha-1d adrenergic receptor / 2
CHEMBL1867 / Alpha-2a adrenergic receptor / 2
CHEMBL1942 / Alpha-2b adrenergic receptor / 2
CHEMBL1916 / Alpha-2c adrenergic receptor / 1
CHEMBL6152 / Alpha-synuclein / 2
CHEMBL1914 / Butyrylcholinesterase / 27
CHEMBL218 / Cannabinoid CB1 receptor / 1
CHEMBL221 / Cyclooxygenase-1 / 1
CHEMBL230 / Cyclooxygenase-2 / 1
CHEMBL3356 / Cytochrome P450 1A2 / 1
CHEMBL2056 / Dopamine D1 receptor / 1
CHEMBL234 / Dopamine D3 receptor / 2
CHEMBL238 / Dopamine transporter / 1
CHEMBL1941 / Histamine H2 receptor / 1
CHEMBL1951 / Monoamine oxidase A / 1
CHEMBL1287628 / NADPH oxidase 1 / 3
CHEMBL222 / Norepinephrine transporter / 3
CHEMBL1833 / Serotonin 2b (5-HT2b) receptor / 2
CHEMBL225 / Serotonin 2c (5-HT2c) receptor / 3
CHEMBL3371 / Serotonin 6 (5-HT6) receptor / 2
CHEMBL228 / Serotonin transporter / 1
CHEMBL287 / Sigma opioid receptor / 2
CHEMBL5685 / Solute carrier family 22 member 1 / 1
DB04896 / Milnacipran / 2 / 2 / 32 / 1 / CHEMBL238 / Dopamine transporter / 7
DB00328 / Indomethacin / 27 / 20 / 31 / 5 / CHEMBL5905 / Aldo-keto reductase family 1 member C1 / 1
CHEMBL5847 / Aldo-keto reductase family 1 member C2 / 11
CHEMBL4999 / Aldo-keto reductase family 1 member C4 / 2
CHEMBL4681 / Aldo-keto-reductase family 1 member C3 / 12
CHEMBL215 / Arachidonate 5-lipoxygenase / 2
DB04794 / Bifonazole / 6 / 4 / 30 / 61 / CHEMBL4235 / 11-beta-hydroxysteroid dehydrogenase 1 / 1
CHEMBL220 / Acetylcholinesterase / 1
CHEMBL2318 / ADAMTS4 / 1
CHEMBL226 / Adenosine A1 receptor / 1
CHEMBL251 / Adenosine A2a receptor / 1
CHEMBL256 / Adenosine A3 receptor / 1
CHEMBL223 / Alpha-1d adrenergic receptor / 1
CHEMBL1867 / Alpha-2a adrenergic receptor / 1
CHEMBL1942 / Alpha-2b adrenergic receptor / 1
CHEMBL2243 / Anandamide amidohydrolase / 1
CHEMBL213 / Beta-1 adrenergic receptor / 1
CHEMBL246 / Beta-3 adrenergic receptor / 1
CHEMBL205 / Carbonic anhydrase II / 1
CHEMBL1795098 / Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1 / 1
CHEMBL2414 / C-C chemokine receptor type 4 / 1
CHEMBL230 / Cyclooxygenase-2 / 1
CHEMBL1798 / Cysteinyl leukotriene receptor 1 / 1
CHEMBL1908 / Cytochrome P450 11B1 / 5
CHEMBL2722 / Cytochrome P450 11B2 / 5
CHEMBL3522 / Cytochrome P450 17A1 / 12
CHEMBL5141 / Cytochrome P450 26A1 / 1
CHEMBL3397 / Cytochrome P450 2C9 / 1
CHEMBL3849 / Cytochrome P450 51 / 1
CHEMBL236 / Delta opioid receptor / 1
CHEMBL2056 / Dopamine D1 receptor / 1
CHEMBL217 / Dopamine D2 receptor / 2
CHEMBL234 / Dopamine D3 receptor / 1
CHEMBL219 / Dopamine D4 receptor / 2
CHEMBL238 / Dopamine transporter / 1
CHEMBL203 / Epidermal growth factor receptor erbB1 / 1
CHEMBL5071 / G protein-coupled receptor 44 / 1
CHEMBL2034 / Glucocorticoid receptor / 1
CHEMBL4508 / Glutaminyl-peptide cyclotransferase / 1
CHEMBL2424 / Glyoxalase I / 1
CHEMBL240 / HERG / 1
CHEMBL231 / Histamine H1 receptor / 1
CHEMBL1941 / Histamine H2 receptor / 1
CHEMBL4029 / Interleukin-8 receptor A / 1
CHEMBL4305 / Intermediate conductance calcium-activated potassium channel protein 4 / 1
CHEMBL237 / Kappa opioid receptor / 1
CHEMBL333 / Matrix metalloproteinase-2 / 1
CHEMBL233 / Mu opioid receptor / 1
CHEMBL216 / Muscarinic acetylcholine receptor M1 / 1
CHEMBL211 / Muscarinic acetylcholine receptor M2 / 1
CHEMBL245 / Muscarinic acetylcholine receptor M3 / 1
CHEMBL1821 / Muscarinic acetylcholine receptor M4 / 1
CHEMBL249 / Neurokinin 1 receptor / 1
CHEMBL2327 / Neurokinin 2 receptor / 1
CHEMBL222 / Norepinephrine transporter / 1
CHEMBL4302 / P-glycoprotein 1 / 1
CHEMBL250 / Platelet activating factor receptor / 1
CHEMBL1824 / Receptor protein-tyrosine kinase erbB-2 / 1
CHEMBL224 / Serotonin 2a (5-HT2a) receptor / 1
CHEMBL1833 / Serotonin 2b (5-HT2b) receptor / 1
CHEMBL225 / Serotonin 2c (5-HT2c) receptor / 1
CHEMBL3371 / Serotonin 6 (5-HT6) receptor / 1
CHEMBL228 / Serotonin transporter / 1
CHEMBL1835 / Thromboxane-A synthase / 1
CHEMBL1841 / Tyrosine-protein kinase FYN / 1
CHEMBL1889 / Vasopressin V1a receptor / 1
CHEMBL1790 / Vasopressin V2 receptor / 1
DB00392 / Ethopropazine / 4 / 1 / 29 / 24 / CHEMBL220 / Acetylcholinesterase / 6
CHEMBL223 / Alpha-1d adrenergic receptor / 3
CHEMBL1867 / Alpha-2a adrenergic receptor / 3
CHEMBL1942 / Alpha-2b adrenergic receptor / 3
CHEMBL1916 / Alpha-2c adrenergic receptor / 2
CHEMBL6152 / Alpha-synuclein / 1
CHEMBL289 / Cytochrome P450 2D6 / 1
CHEMBL2056 / Dopamine D1 receptor / 2
CHEMBL217 / Dopamine D2 receptor / 2
CHEMBL234 / Dopamine D3 receptor / 3
CHEMBL231 / Histamine H1 receptor / 3
CHEMBL1941 / Histamine H2 receptor / 2
CHEMBL245 / Muscarinic acetylcholine receptor M3 / 3
CHEMBL1821 / Muscarinic acetylcholine receptor M4 / 3
CHEMBL2035 / Muscarinic acetylcholine receptor M5 / 3
CHEMBL1287628 / NADPH oxidase 1 / 1
CHEMBL222 / Norepinephrine transporter / 3
CHEMBL224 / Serotonin 2a (5-HT2a) receptor / 3
CHEMBL1833 / Serotonin 2b (5-HT2b) receptor / 3
CHEMBL225 / Serotonin 2c (5-HT2c) receptor / 3
CHEMBL3371 / Serotonin 6 (5-HT6) receptor / 3
CHEMBL228 / Serotonin transporter / 2
CHEMBL287 / Sigma opioid receptor / 3
CHEMBL5685 / Solute carrier family 22 member 1 / 2
DB00902 / Methdilazine / 1 / NA / 29 / 33 / CHEMBL220 / Acetylcholinesterase / 6
CHEMBL256 / Adenosine A3 receptor / 1
CHEMBL223 / Alpha-1d adrenergic receptor / 3
CHEMBL1867 / Alpha-2a adrenergic receptor / 3
CHEMBL1942 / Alpha-2b adrenergic receptor / 3
CHEMBL1916 / Alpha-2c adrenergic receptor / 2
CHEMBL6152 / Alpha-synuclein / 2
CHEMBL1914 / Butyrylcholinesterase / 22
CHEMBL218 / Cannabinoid CB1 receptor / 1
CHEMBL221 / Cyclooxygenase-1 / 1
CHEMBL230 / Cyclooxygenase-2 / 1
CHEMBL3356 / Cytochrome P450 1A2 / 1
CHEMBL289 / Cytochrome P450 2D6 / 1
CHEMBL2056 / Dopamine D1 receptor / 2
CHEMBL217 / Dopamine D2 receptor / 2
CHEMBL234 / Dopamine D3 receptor / 3
CHEMBL238 / Dopamine transporter / 1
CHEMBL1941 / Histamine H2 receptor / 2
CHEMBL1951 / Monoamine oxidase A / 1
CHEMBL216 / Muscarinic acetylcholine receptor M1 / 3
CHEMBL211 / Muscarinic acetylcholine receptor M2 / 3
CHEMBL245 / Muscarinic acetylcholine receptor M3 / 3
CHEMBL1821 / Muscarinic acetylcholine receptor M4 / 3
CHEMBL2035 / Muscarinic acetylcholine receptor M5 / 3
CHEMBL1287628 / NADPH oxidase 1 / 3
CHEMBL222 / Norepinephrine transporter / 4
CHEMBL224 / Serotonin 2a (5-HT2a) receptor / 3
CHEMBL1833 / Serotonin 2b (5-HT2b) receptor / 3
CHEMBL225 / Serotonin 2c (5-HT2c) receptor / 4
CHEMBL3371 / Serotonin 6 (5-HT6) receptor / 3
CHEMBL228 / Serotonin transporter / 2
CHEMBL287 / Sigma opioid receptor / 3
CHEMBL5685 / Solute carrier family 22 member 1 / 2
DB01261 / Sitagliptin / 4 / 2 / 29 / 2 / CHEMBL4793 / Dipeptidyl peptidase IX / 4
CHEMBL4657 / Dipeptidyl peptidase VIII / 12