Table 1.
Test compounds reported to cause phospholipidosis
| Generic name | UPAC Designation | CAS Number | Indication | ClogP | pKa (basic) | Ploemen Value | Pred Ploemen | Pred modified Ploemen | LPLA2 IC50 (μM) | In Vitro PLD | In Vivo PLD | Refs |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Alprenolol | 1-(o-allylphenoxy)-3-(isopropylamino)-2-propanol | 13707-88-5 | Antihypertensive, antiarrhythmic, sympatholytic agent | 3.1 | 9.67 | 103 | + | + | 172.7 | Yes | (28, 29) | |
| Alverine | ethyl bis (3-phenylpropyl)amine | 150-59-4 | Antidiarrheal | 5.73 | 10.44 | 142 | + | + | 40.01 | Yes | (28, 30) | |
| Ambroxol | 2-amino-3,5-dibromo-N-(trans-4-hydroxycyclohexyl) benzylamine | 28828-92-4 | Mucolytic | 3.72 | 9.01 | 95 | + | + | 59 | Yes | (28, 31) | |
| Amiodarone | {2-[4-(2-butyl-1-benzofuran-3-carbonyl)-2,6-diiodophenoxy] ethyl} diethyl amine | 1951-25-3 | Antiarrhythmic | 7.57 | 8.47 | 130 | + | + | 8.3 | Yes | H,R | (16, 25, 27, 28, 32, 33, 34, 35, 36, 37, 38) |
| Amitriptyline | dimethyl(3-{tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaen-2-ylidene}propyl)amine | 50-48-6 | Antidepressant | 5.1 | 9.76 | 121 | + | + | 14.7 | Yes | R | (11, 16, 27, 28, 35, 36, 39, 40) |
| Amorolfine | 2R,6S-2,6-dimethyl-4-(2-{[4-(2-methylbutan-2-yl) phenyl] methyl}propyl)morpholine | 78613-35-1 | Antifungal | 5.62 | 8.49 | 104 | + | + | 41.47 | Yes | (28, 30) | |
| Anastrozole | 2;2″-[5-(1H-1;2;4-Triazol-1-ylmethyl)-1,3-phenylene]bis(2-methyl-propiononitrile) | 120511-73-1 | Chemotherapy | 2.31 | 2 | 9.3 | - | - | 4.82 | Yes | (41, 42) | |
| Astemizole | 1-(4-fluorobenzyl)-2-(1-[4-methoxyphenethyl]piperidin-4-yl)aminobenzimidazole | 68844-77-9 | Antihistamine | 5.92 | 8.75 | 112 | + | + | 8.19 | Yes | (28, 33, 40) | |
| ay-9944 |
trans-1,4- bis(2-chlorobenzylaminomethyl) cyclohexane |
366-93-8 | Hypocholestrol-emic | 6.4 | 9.1 | 124 | - | + | 116 | Yes | R,Ra, M | (16, 43, 44, 45, 46) |
| Benzbromarone | 2,6-dibromo-4-(2-ethyl-1-benzofuran-3-carbonyl)phenol | 3562-84-3 | Xanthine oxidase inhibitor | 5.52 | -3.8 | 30.5 | - | - | 3.8 | Yes | (28, 32) | |
| Benfluorex | N-(1-methyl-2-(3-[trifluoromethyl]-phenyl)ethyl)amino ethanol benzoate ester | 23642-66-2 | Anorectic and hypolipidemic | 4.26 | 9.14 | 102 | + | + | 19.9 | Yes | (35, 47, 48) | |
| Bepridil hydrochloride | 1-isobutoxy-2-pyrrolidino-3-(N-benzylanilino) propane hydrochloride | 74764-40-2 | Calcium channel blocker | 5.33 | 9.16 | 112 | + | + | 7.17 | Yes | (28, 36) | |
| Betaxolol | 1-{4-[2-(cyclopropylmethoxy) ethyl] phenoxy}-3-[(propan-2-yl) amino]propan-2-ol | 63659-18-7 | Beta blocker | 2.81 | 9.67 | 101 | + | + | 0 | Yes | (28, 40) | |
| Bromhexine | 2-amino-3,5-dibromo-N-cyclohexyl-N-methylbenzylamine hydrochloride | 611-75-6 | Mucolytic | 4.08 | 9.32 | 104 | + | + | 30.78 | Yes | (28, 31, 49, 50) | |
| Buclizine | 1-((4-chlorophenyl)phenylmethyl)-4-((4-(1,1-dimethylethyl)phenyl)methyl)piperazine | 82-95-1 | Antihistamine | 6.16 | 8.04 | 103 | + | + | 9.13 | Yes | (12, 28) | |
| Bromocriptine | (4R,7R)-10-bromo-N-[(1S,2S,4R,7S)-2-hydroxy-7-(2-methylpropyl)-5,8-dioxo-4-(propan-2-yl)-3-oxa-6,9-diazatricyclo[7.3.0.0ˆ{2,6}]dodecan-4-yl]-6-methyl-6,11diazatetracyclo[7.6.1.0ˆ{2,7}.0ˆ{12,16}]hexadeca-1(16),2,9,12,14-pentaene-4-carboxamide | 25614-03-3 | Dopamine promoter | 3.2 | 6.71 | 55 | - | + | 125 | Yes | (28, 51) | |
| Chloroquine | 7-chloro-N-[5-(diethylamino)pentan-2-yl]quinolin-4-amine | 54-05-7 | Immunosuppress-sive and anti-parasitic | 4.63 | 10.32 | 128 | + | + | 655 | Yes | H, R, D, M | (28, 34, 36, 37, 38, 40, 52, 53, 54, 55) |
| Chlorpheniramine | [3-(4-chlorophenyl)-3-(pyridin-2-yl) propyl] dimethylamine | 132-22-9 | Antihistamine | 3.38 | 9.47 | 101 | + | + | 147 | Yes | (28, 35, 56) | |
| Chlorprothixene | 3-[(9Z)-2-chloro-9H-thioxanthen-9-ylidene]propyl}dimethylamine | 11-59-7 | Antipsychotic | 5.18 | 9.76 | 122 | + | + | 7.78 | Yes | (28) | |
| Chlorpromazine | [3-(2-chloro-10H-phenothiazin-10-yl)propyl] dimethylamine | 50-53-3 | Antipsychotic | 5.41 | 9.3 | 116 | + | + | 9.01 | Yes | R, D | (16, 27, 28, 34, 36, 37, 39, 40) |
| Cinnarizine | 1-(diphenyl methyl)-4-(3-phenylprop-2-en-1-yl) piperazine | 298-57-7 | Antihistamine | 5.77 | 8.44 | 105 | + | + | 40.6 | Yes | (28, 57) | |
| Citalopram | 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile | 59729-33-8 | Antidepressant | 3.76 | 9.78 | 110 | + | + | 19.5 | Yes | Yes | (12, 27, 28, 34, 35, 36, 37, 40) |
| Clemastine | (2R)-2-{2-[(1R)-1-(4-chlorophenyl)-1-phenylethoxy] ethyl-1-methylpyrrolidine | 14976-57-9 | Antihistamine | 5.29 | 9.55 | 119 | + | + | 13.21 | Yes | (28) | |
| Clenbuterol | 4-amino-3,5-dichloro-α-[[(1,1-dimethylethyl)amino]methyl]-benzenemethanol, monohydrochloride | 21898-19-1 | Muscle relaxer decongestant, bronchodilator | 2.94 | 9.63 | 101 | + | + | 7298 | Yes | (28) | |
| Clindamycin | (2S,4R)-N-{2-chloro-1-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(methylsulfanyl)oxan-2-yl]propyl}-1-methyl-4-propylpyrrolidine-2-carboxamide | 18323-44-9 | Antibiotic | 2.16 | 7.55 | 61.7 | - | + | ND | Yes | Yes | (12, 28, 36, 40) |
| Clofazimine | N,5-bis(4-chlorophenyl)-3,5-dihydro-3-(isopropylimino)phenazin-2-amine | 2030-63-9 | Anti-mycobacterial, anti-inflammatory properties | 7.66 | 9.29 | 145 | + | + | 10.8 | Yes | (28, 58, 59) | |
| Clomipramine | (3-{14-chloro-2-azatricyclo[9.4.0.03,8]pentadeca-1(11), 3,5,7,12,14-hexaen-2-yl}propyl)dimethylamine | 303-49-1 | Antidepressant | 5.04 | 9.2 | 104 | + | + | 17 | Yes | Yes | (16, 28, 34, 35, 36, 37, 39) |
| Cloperastin | 1-{2-[(4-chlorophenyl) (phenyl)methoxy] ethyl} piperidine | 3703-76-2 | Antihistamine | 5.11 | 8.82 | 104 | + | + | 40.9 | Yes | (28, 30) | |
| Clozapine | 8-Chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e][1,4]-diazepine | 34233-69-7 | Antipsychotic | 3.23 | 7.35 | 64.5 | - | + | 10.8 | Yes | Yes | (16, 28, 34, 39, 40) |
| Corticosterone | (1S,2R,10S,11S,14S,15S,17S)-17-hydroxy-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.02,7.011,15]heptadec-6-en-5-one | 50-22-6 | Glucocorticoid | 2.09 | -0.26 | 4.4 | - | - | 163 | Yes | (28, 38) | |
| Cyclazosin | 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furanylcarbonyl) decahydroquinoxaline | 146929-33-1 | Adrenoceptor antagonist | 3.4 | 9.89 | 109 | + | + | 30.75 | Yes | (28, 37) | |
| Cyclobenzaprine | dimethyl(3-{tricyclo[9.4.0.03,8]pentadeca-1(15),3,5, 7,9,11,13-heptaen-2-ylidene}propyl)amine | 303-53-7 | Muscle relaxant | 4.73 | 8.47 | 94 | + | + | 6.24 | Yes | Yes | (37) |
| Cyclopentolate | 2-(dimethylamino)ethyl 2-(1-hydroxycyclopentyl)-2-phenylacetate | 515-15-2 | Anticholinergic | 2.32 | 8.42 | 76 | - | + | 32.2 | Yes | (28, 60, 61) | |
| Desipramine | (3-{2-azatricyclo [9.4.0.0] pentadeca-1(15),3,5,7,11,13-hexaen-2-yl}propyl)(methyl)amine | 58-28-6 | Antidepressant | 4.02 | 10.02 | 117 | + | + | 25.69 | Yes | R | (35, 36, 37, 40, 62) |
| Dibenzosuberane | 10,11-dihydro-5H-dibenzo [a, d] cycloheptene-833-48-7 | 833-48-7 | Protein inhibitor | 4.7 | 10 | 122 | + | + | 346 | Yes | (28) | |
| Diphenhydramine | 2-[(4-methyl-α-phenyl benzyl) oxy]ethyl (dimethyl) ammonium chloride | 147-24-0 | Antihistamine | 3.27 | 8.87 | 89.4 | - | + | 270 | Yes | (28) | |
| Doxepin | dimethyl(3-{9-oxatricyclo[9.4.0.0ˆ[1]]pentadeca-1(15),3,5,7,11,13-hexaen-2-ylidene}propyl)amine | 1668-19-5 | Psychotropic | 4.29 | 9.76 | 114 | + | + | 301 | Yes | Yes | (28, 37) |
| Drofenine | hexahydroadiphenine | 548-66-3 | Anticholinergic | 5.3 | 9.21 | 113 | + | + | 7.29 | Yes | (35, 63) | |
| Dutasteride | (1S,2R,7R,10S,11S,14S,15S)-N-[2,5-bis (trifluoromethyl) phenyl]-2,15-dimethyl-5-oxo-6-azatetracyclo[8.7.0.02,7.011,15]heptadec-3-ene-14-carboxamide | 164656-23-9 | 5α-reductase inhibitor | 6.8 | 2.17 | 50.9 | + | + | 1048 | Yes | (28) | |
| Encainide | 4-methoxy-N-{2-[2-(1-methylpiperidin-2-yl)ethyl] phenyl} benzamide | 66778-36-7 | Sodium channel blocker | 4 | 9.41 | 105 | + | + | 76.09 | Yes | (28, 64) | |
| Erythromycin | (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-6-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}-14-ethyl-7,12,13-trihydroxy-4-{[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy}-3,5,7,9,11,13-hexamethyl-1-oxacyclotetradecane-2,10-dione | 114-07-8 | Bacteriostatic antibiotic | 2.37 | 8.38 | 75.9 | + | 117 | Yes | R, D | (28, 34, 36, 39, 65) | |
| Etomidate | ethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate | 33125-97-2 | Anesthetic | 3 | 4.54 | 29.6 | - | - | 1155 | Yes | (28, 40) | |
| Fenofibrate | 2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropanoic acid isopropyl ester | 49562-28-9 | Cholesterol lowering | 5.3 | -4.9 | 28.1 | - | 31.58 | 2.25 | Yes | (28, 66) | |
| Fexofenadine | 2-(4-{1-hydroxy-4-[4-(hydroxydiphenylmethyl) piperidin-1-yl]butyl} phenyl)-2-methylpropanoic acid | 83799-24-0 | Antihistamine | 5.02 | 9.01 | 106 | + | + | 179 | Yes | (28, 67) | |
| Fipexide | 1-(2-[4-chlorophenoxy]acetyl)-4-(3,4-methylenedioxybenzyl)piperazine | 34161-24-5 | Attention deficit | 2.95 | 6.09 | 45.7 | - | - | 17.19 | Yes | (28) | |
| Flunarizine | 1-[bis(4-fluorophenyl)methyl]-4-[(2E)-3-phenylprop-2-en-1-yl]piperazine | 52468-60-7 | Calcium entry blocker | 5.3 | 7.6 | 85.9 | - | + | 7.49 | Yes | (28, 68) | |
| Fluoxetine | methyl({3-phenyl-3-[4-(trifluoromethyl) phenoxy] propyl}) amine | 54910-89-3 | Antidepressant | 4.5 | 9.8 | 112 | + | + | 13.5 | Yes | H,R,M | (16, 27, 28, 34, 35, 36, 37, 39, 40, 69, 70) |
| Flufenamic acid | 2-{[3-(trifluoromethyl)phenyl]amino}benzoic acid | 530-78-9 | Analgesic, anti-inflammatory, antipyretic | 5.25 | -2.1 | 32 | - | - | 177.9 | Yes | (28, 71) | |
| Gentisic acid | 2,5-dihydroxybenzoic acid sodium salt | 4955-90-2 | Anti-inflammatory, antioxidant | -1.1 | -5.9 | 34.8 | - | - | 99.4 | Yes | (28, 72) | |
| Hydroxyzine | 2-(2-{4-[(4-chlorophenyl) (phenyl) methyl] piperazin-1-yl} ethoxy)ethan-1-ol | 68-88-2 | Antihistaminic | 3.43 | 7.82 | 72.9 | - | + | 63 | R | (34, 36, 55, 73) | |
| Imipramine | (3-{2-azatricyclo[9.4.0.03,8]pentadeca-1(15),3, 5,7,11, 13-hexaen-2-yl}propyl)dimethylamine | 50-49-7 | Antidepressant | 4.8 | 9.2 | 108 | + | + | 27.6 | Yes | R | (16, 28, 34, 35, 36, 37, 40, 74, 75) |
| Indoramin | N-{1-[2-(1H-indol-3-yl)ethyl]piperidin-4-yl} benzamide | 26844-12-2 | Antiadrenergic | 4.02 | 9.59 | 108 | + | + | 123.9 | Yes | R | (28, 36, 40) |
| Ketoconazole | 1-[4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazole-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]ethan-1-one | 65277-42-1 | Antifungal | 4.35 | 6.75 | 64.5 | - | + | 39 | Yes | M | (16, 27, 28, 34, 36, 37, 40) |
| Ketotifen | 4-(1-methylpiperidin-4-ylidene)-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-9,10-dione | 34580-14-8 | Antihistamine | 2.2 | 7.15 | 56 | - | + | 19.68 | Yes | (16, 28, 36, 76) | |
| Lercanidipine | 3-{1-[(3,3-diphenylpropyl)(methyl)amino]-2-methylpropan-2-yl} 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate | 100427-26-7 | Calcium channel blocker | 6.4 | 9.36 | 129 | + | + | 37.25 | Yes | (28, 77) | |
| Lofepramine | 2-[(3-{2-azatricyclo[9.4.0.0ˆ{3,8}]pentadeca-1(15),3,5,7,11,13-hexaen-2-yl}propyl) (methyl) amino]-1-(4-chlorophenyl) ethan-1-one | 23047-25-8 | Antidepressant | 6.11 | 6.53 | 80 | - | + | 13.25 | Yes | (28) | |
| Loperamide | 4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-N,N-dimethyl-2,2-diphenylbutanamide | 53179-11-6 | Antidiarrheal | 4.44 | 9.41 | 108 | + | + | 149.12 | Yes | (28) | |
| Loratadine | ethyl 4-{13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene}piperidine-1-carboxylate | 79794-75-5 | Antihistamine | 4.8 | 4.33 | 41.8 | - | - | 8.94 | Yes | (16, 28, 36, 37, 40, 78) | |
| Mannitol | (2R,3R,4R,5R)-hexane-1,2,3,4,5,6-hexol | 69-65-8 | Osmotic diuretic | -2.7 | 12.3 | 159 | + | + | 160 | Yes | (28, 38, 79) | |
| Maprotiline | methyl(3-{tetracyclo [6.6.2.02,7.09,14]hexadeca-2,4,6,9,11, 13-hexaen-1-yl}propyl)amine | 10262-69-8 | Antidepressant | 4.82 | 10.54 | 134 | + | + | 12 | R | (34, 35, 36, 79, 80) | |
| Mebeverine | 4-{ethyl[1-(4-methoxyphenyl)propan-2-yl]amino}butyl 3,4-dimethoxybenzoate | 2743-45-9 | Anti-diarrheal | 4.6 | 10.31 | 127 | + | + | 417 | Yes | (28) | |
| Memantine | 3,5-Dimethyl-1-adamantanamine hydrochloride | 41100-52-1 | NMDA receptor antagonist | 3.32 | 10.7 | 125 | + | + | 35.7 | Yes | (35, 37, 81, 82) | |
| Methapyrilene | N-[2-(dimethyl amino)ethyl]-N-[(thiophen-2-yl) methyl ]pyridin-2-amine | 91-80-5 | Antihistamine | 2.87 | 8.85 | 86.6 | - | + | ND | Yes | (28) | |
| Mianserin | 5-methyl-2,5 diazatetracyclo [13.4.0.02,7.08,1³] nonadeca-1(19),8,10,12,15,17-hexaene | 24219-97-4 | Antidepressant | 3.52 | 6.9 | 60.3 | - | + | 29.98 | Yes | (28, 33, 36) | |
| Mifepristone | (1S,3aS,3bS,10R,11aS)-10-[4-(dimethylamino )phenyl]-1-hydroxy-11a-methyl-1-(prop-1-yn-1-yl)-1H,2H,3H,3aH, 3bH,4H,5H,7H,8H, 9H,10H,11H,11aH-cyclopenta[a]phenanthren-7-one | 84371-65-3 | Progesterone blocker | 5.3 | 4.89 | 52 | + | - | 27.69 | Yes | (28) | |
| Mirtazapine | 5-methyl-2,5,19-triazatetracyclo [13.4.0.02,7.08,1³] nonadeca-1(15),8,10,12,16,18-hexaene | 85650-52-8 | Antidepressant | 2.9 | 6.67 | 52.9 | - | + | 8.7 | Yes | (28, 83, 84) | |
| Mitotane | 1-chloro-4-[2,2-dichloro-1-(2-chlorophenyl) ethyl] benzene | 53-19-0 | Chemotherapy | 6 | 36 | - | - | 132.1 | Yes | (28, 85) | ||
| Naphazoline | 2-(naphthalen-1-ylmethyl)-4,5-dihydro-1H-imidazole | 835-31-4 | Sympathomimetic | 3.44 | 10.19 | 115 | + | + | 6.98 | Yes | (35) | |
| Oxolamine citrate | diethyl[2-(3-phenyl-1,2,4-oxadiazol-5-yl)ethyl]amine | 959-14-8 | Anti-psychotic | 2.7 | 8.96 | 87.6 | - | + | 369 | Yes | (28, 86) | |
| Oxybutynin | α-phenylcyclohexaneglycolic acid 4-(diethyl amino)-2-butynyl ster hydrochloride | 1508-65-2 | Anticholinergic | 4.36 | 8.77 | 95.9 | + | + | 26.39 | Yes | (28) | |
| Pantoprazole | 6-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl) methanesulfinyl] -1H-1,3-benzodiazole | 102625-70-7 | Proton pump inhibitor | 2.11 | 3.55 | 17.1 | - | - | 6.23 | Yes | (28, 35, 87) | |
| Paroxetine | (3S,4R)-3-[(2H-1,3-benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)piperidine | 61869-08-7 | Antidepressant | 3.1 | 9.77 | 105 | + | + | 5.12 | R | (28, 36, 37, 69) | |
| Penfluridol | 1-[4,4-bis(4-fluorophenyl)butyl]-4-[4-chloro-3-(trifluoromethyl) phenyl]piperidin-4-ol | 26864-56-2 | Antipsychotic | 6.09 | 8.96 | 117 | - | + | 9.09 | Yes | (28, 36, 63) | |
| Perhexiline | 2-(2,2-dicyclohexylethyl) piperidine | 6621-47-2 | Coronary vasodilator | 6.2 | 10.58 | 150 | + | + | 11.72 | Yes | H,R,M | (16, 28, 34, 35, 36, 40, 88, 89, 90) |
| Perphenazine | 2-{4-[3-(2-chloro-10H-phenothiazin-10-yl)propyl] piperazin-1-yl ethan-1-ol | 58-39-9 | Antipsychotic | 4.2 | 8.21 | 85 | - | + | 3.92 | Yes | (28) | |
| Phenacetin | N-(4-ethoxyphenyl) acetamide | 62-44-2 | Non-steroidal | 1.58 | -4.2 | 2.5 | - | - | 2140 | Yes | R | (6, 28, 40, 79, 91) |
| Pimozide | 1-{1-[4,4-bis(4-fluorophenyl)butyl]piperidin-4-yl}-2,3-dihydro-1H-1,3-benzodiazol-2-one | 2062-78-4 | Antipsychotic | 6.36 | 8.38 | 111 | + | + | 10.6 | Yes | (28, 92) | |
| Pirenperone | 3-[2-[4-(4-Fluorobenzoyl)-1-piperidinyl]ethyl]-2-methyl-4H-pyrido-[1,2-a] pyrimidin-4-one | 75444-65-4 | Antipsychotic | 2.6 | 8.02 | 71.1 | - | + | 232.6 | Yes | (28, 93) | |
| Pranlukast | N-[4-oxo-2-(2H-1,2,3,4-tetrazol-5-yl)-4H-chromen-8-yl]-4-(4-phenylbutoxy)benzamide | 103177-37-3 | Antiasthmatic | 4.82 | -1.7 | 23.2 | - | - | ND | Yes | (28, 30) | |
| Pridinol | 1,1-diphenyl-3-(piperidin-1-yl)propan-1-ol | 511-45-5 | Muscle relaxant | 3.69 | 9.34 | 101 | + | + | 285.4 | Yes | (28, 94) | |
| Profenamine | diethyl[1-(10H-phenothiazin-10-yl)propan-2-yl]amine | 522-00-9 | Antidyskinetic | 5.75 | 9.6 | 125 | + | + | 8.7 | Yes | (28, 95) | |
| Progesterone | (1S,3aS,3bS,9aR,9bS,11aS)-1-acetyl-9a,11a-dimethyl-1H,2H,3H, 3aH,3bH,4H,5H, 7H,8H,9H,9 aH,9bH, 10H,11H,11aH-cyclopenta [a] phenanthren-7-one | 57-83-0 | Hormone | 3.58 | -4.8 | 12.8 | - | - | 10.52 | Yes | (28, 96) | |
| Promazine | dimethyl[3-(10H-phenothiazin-10-yl)propyl]amine | 58-40-2 | Antipsychotic | 4.55 | 9.2 | 105 | + | + | 39 | Yes | R | (28, 34, 35, 40) |
| Promethazine | dimethyl[1-(10H-phenothiazin-10-yl)propan-2-yl] amine | 60-87-7 | Antihistamine | 4.81 | 9.05 | 105 | + | + | 40.3 | Yes | Yes | (28, 37, 40) |
| Propafenone | 1-{2-[2-hydroxy-3-(propylamino)propoxy]phenyl}-3-phenylpropan-1-one | 54063-53-5 | Antiarrhythmic | 3.1 | 9.63 | 102 | + | + | 48.22 | Yes | (28, 97) | |
| Proparacaine | 2-(diethylamino)ethyl 3-amino-4-propoxybenzoate | 499-67-2 | Anesthetic | 2.5 | 8.56 | 79.5 | - | + | 2469 | Yes | (28, 60) | |
| Propranolol | 1-(naphthalen-1-yloxy)-3-[(propan-2-yl)amino]propan-2-ol | 525-66-6 | Antihypertensive | 3.48 | 9.67 | 106 | + | + | 49.9 | Yes | (1, 28, 34, 35, 36, 37, 40) | |
| Pyrilamine | N-[2-(dimethyl amino)ethyl]-N-[(4-methoxyphenyl) methyl]pyridin-2-amine | 91-84-9 | Antihistamine | 3.27 | 8.76 | 87.4 | - | + | 214 | Yes | (28, 98) | |
| Quinacrine | 6- chloro-9-(4-diethylamino-1-methylbutylamino)-2-methoxyacridine dihydrochloride | 69-05-6 | Antimalarial and antibiotic | 5.5 | 10.33 | 137 | + | + | 30.13 | Yes | R | (28, 34, 35, 36, 37, 40, 99) |
| Quinine | (R)-[(1S,2S,4S,5R)-5-ethenyl-1-azabicyclo [2.2.2]octan-2-yl](6-methoxyquinolin-4-yl)methanol | 130-95-0 | Antimalarial | 3.34 | 9.05 | 93.7 | + | + | 164 | Yes | (36, 40) | |
| Repaglinide | 2-ethoxy-4-[2-({3-methyl-1-[2-(1-piperidinyl)phenyl]butyl}amino)-2-oxoethyl]benzoic acid | 135062-02-1 | Antihyperglycemic | 5.9 | 4.28 | 53.1 | - | + | 86.49 | Yes | (28, 29) | |
| Retinol | (2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraen-1-ol | 68-26-8 | Vitamin A | 5.68 | -2.2 | 37.1 | - | - | 52.52 | Yes | (28, 100) | |
| Ropinirole | 4-[2-(dipropylamino)ethyl]-2,3-dihydro-1H-indol-2-one | 91374-21-9 | Dopamine agonist | 3.06 | 10.17 | 113 | + | + | ND | Yes | (28, 101) | |
| Sertraline | (1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine | 79617-96-2 | Antidepressant | 5.15 | 9.85 | 123 | + | - | 8.6 | Yes | Yes | (16, 27, 28, 34, 35, 36, 37, 40) |
| Spiperone | 8-[3-(p-fluor benzoyl)propyl]-1-phenyl-1,3,8-triazaspiro [4.5]decan-4-one | 749-02-0 | Antipsychotic | 3.03 | 8.89 | 88.2 | - | + | 519.2 | Yes | (28, 37) | |
| Sulindac | 2-[(1Z)-5-fluoro-1-[(4-methanesulfinylphenyl)methylidene]-2-methyl-1H-inden-3-yl]acetic acid | 38194-50-2 | Nonsteroidal | 3.42 | -6.7 | 11.7 | - | - | 10.93 | Yes | (28, 36, 102) | |
| Sulpiride | N-[(1-ethylpyrrolidin-2-yl)methyl]-2-methoxy-5-sulfamoylbenzamide | 15676-16-1 | Antidepressant, antipsychotic | 1.2 | 8.4 | 71.8 | - | - | ND | Yes | (103) | |
| Suramin | 8-{4-methyl-3-[3-({[3-({2-methyl-5-[(4,6,8-trisulfonaphthalen-1yl)carbamoyl]phenyl}carbamoyl)phenyl]carbamoyl}amino)benzamido]benzamido}naphthalene-1,3,5-trisulfonic acid | 129-46-4 | Antineoplastic | 5.58 | -6 | 31.1 | - | - | 35.55 | Yes | R | (28, 104, 105) |
| Tacrine | 1,2,3,4-tetrahydroacridin-9-amine | 321-64-2 | Cholinesterase inhibitor | 2.71 | 8.95 | 87.5 | - | + | 63.5 | Yes | (28) | |
| Tamoxifen | (2-{4-[(1Z)-1,2-diphenylbut-1-en-1-yl]phenoxy} ethyl) dimethylamine | 10540-29-1 | Antiestrogenic | 5.93 | 8.76 | 112 | + | + | 7.7 | Yes | R | (16, 27, 28, 34, 35, 36, 39) |
| Tetracaine | 2-(dimethylamino)ethyl 4-(butylamino)benzoate | 94-24-6 | Anaesthetic | 3.54 | 8.42 | 83.4 | - | + | 333 | Yes | (28) | |
| Thioridazine | 10-[2-(1-methylpiperidin-2-yl)ethyl]-2-(methylsulfanyl) -10H-phenothiazine | 50-52-2 | Antipsychotic | 5.9 | 8.93 | 115 | + | + | 38 | Yes | R | (16, 28, 36, 40, 106) |
| Tobramycin | O-[3-amino-3-deoxy-α-D-glucopyranosyl-(1→6)]-O-[2,6-diamino-2,3,6-trideoxy-α- D-ribohexopyranosyl-(1→4)]-2-deoxy-D-streptamine | 32986-56-4 | Antibiotic | -5.8 | 9.8 | 130 | + | + | 33.03 | Yes | R,H | (28, 36, 40, 107, 108, 109) |
| Trimipramine | (3-{2-azatricyclo[9.4.0.0³,8]pentadeca-1(15),3,5,7,11, 13-hexaen-2-yl}-2-methylpropyl)dimethylamine | 739-71-9 | Antidepressant | 4.67 | 9.42 | 111 | + | + | 267.9 | Yes | (7, 28, 40) | |
| Triparanol | 1-(4-(2-diethylaminoethoxy)phenyl)-1-p-tolyl-2-(4-chlorophenyl)ethanol | 78-41-1 | Cholesterol synthesis inhibitor | 6.2 | 13.44 | 219 | + | + | 7.8 | Yes | R, M, Ha | (28, 33, 35, 73, 110, 111, 112, 113) |
| Vinblastine | methyl (1R,9R,10S,11R,12R,19R)-11-(acetyloxy)-12-ethyl-4-[(13S,15R,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo [13.3.1.0ˆ[1].0ˆ[1]]nonadeca-4(12),5(10),6,8-tetraen-13-yl]-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo [10.6.1.0ˆ[1].0ˆ[1] .0ˆ[3]] nonadeca-2,4,6,13-tetraene-10-carboxylate | 865-21-4 | Chemotherapeutic | 3.7 | 8.86 | 92.2 | + | + | 2123 | Yes | (28, 97) | |
| Warfarin | 4-hydroxy-3-(3-oxo-1-phenylbutyl)-2H-chromen-2-one | 81-81-2 | Anticoagulant | 2.41 | -6.6 | 49.4 | - | - | 94 | Yes | (28, 114) | |
| Yohimbine | methyl (1S,15R,18S,19R,20S)-18-hydroxy-3,13-diazapentacyclo [11.8.0.02,10.04,9.015,20]henicosa-2(10),4,6,8-tetraene-19-carboxylate | 146-48-5 | Alpha adrenergic antagonist | 2.73 | 7.65 | 66 | - | + | 200 | Yes | (28) | |
| Zafirlukast | cyclopentyl N-[3-({2-methoxy-4-[(2-methylbenzenesulfonyl) carbamoyl]phenyl}methyl)-1-methyl-1H-indol-5-yl]carbamate | 107753-78-6 | Leukotriene receptor antagonist | 5.4 | -1.1 | 29.2 | - | - | 3.1 | Yes | (35) |
The generic name, International Union of Pure and Applied Chemistry (IUPAC) designation, chemical abstracts registry (CAS) number, and clinical indication are provided. Chemical properties, including ClogP and pKa (basic) were obtained from the Pubchem and chEMBL databases of bioactive molecules and used to calculate the Ploemen value for each compound. By convention, negative pKa values were assigned a value of 0 for calculation of the Ploemen number and would be predicted negative based on pKa values of less than 8 or 6 for the Ploemen and modified Ploemen models respectively (Table 3). The species for in vivo data are designated as human (H), dog (D), rat (R), mouse (M), and hamster (Ha). LPLA2 IC50 denotes the concentration at which 50% of the LPLA2 dependent 1-O-acyl N-acetylsphingosine synthase activity is observed.