Table 2.
Test compounds not previously associated with phospholipidosis
| Generic Name | UPAC Designation | CAS Number | Indication | ClogP | pKa (basic) | Ploemen Value | Pred Ploemen | Pred Mod Ploemen |
LPLA2 IC50 (μM) |
|---|---|---|---|---|---|---|---|---|---|
| Amisulpride | 4-amino-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-2-methoxybenzamide | 71675-85-9 | antipsychotic | 1.5 | 7.05 | 52 | - | - | 1915 |
| Allopurinol | 3-(4H-1,2,4-triazol-4-yl)-1H-pyrazole-4-carboxamide | 315-30-0 | xanthine oxidase inhibitor | -0.55 | 2.57 | 6.9 | - | - | ND |
| Atovaquone | 2-hydroxy-3-[(1r,4r)-4-(4-chlorophenyl) cyclohexyl] -1,4-dihydronaphthalene-1,4-dione | 95233-18-4 | anti-pneumocystis, anti-malarial | 1.59 | 8.16 | 69.1 | - | - | ND |
| Atropine | (1R,3R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl 3-hydroxy-2-phenylpropanoate | 51-55-8 | antimuscarinic | 1.83 | 9.39 | 91.5 | - | - | 1874 |
| Azaperone | 1-(4-fluorophenyl)-4-[4-(pyridin-2-yl)piperazin-1-yl] butan-1-one | 1649-18-9 | tranquilizer | 2.73 | 7.16 | 58.7 | - | + | ND |
| Benztropine | (1R,3R,5S)-3-(diphenylmethoxy)-8-methyl-8-azabicyclo[3.2.1]octane | 86-13-5 | antitremor | 4.27 | 9.54 | 109 | + | + | 58.97 |
| 18 Beta-glycyrrhetinic acid | 3β-hydroxy-11-oxo-18β,20β-olean-12-en-29-oic acid | 471-53-4 | anti-inflammatory, antioxidant | 3.7 | 16 | 270 | + | + | 2432 |
| Butenafine | [(4-tert-butylphenyl)methyl](methyl)(naphthalen-1-ylmethyl)amine | 101828-21-1 | antifungal | 5.85 | 9.23 | 119 | + | + | 41.2 |
| Carbamazepine | 2-azatricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,9,11,13-heptaene-2-carboxamide | 298-46-4 | anticonvulsant | 2.77 | -3.8 | 7.7 | - | - | 105.6 |
| Clomifene | 2-[4-(2-chloro-1,2-diphenylethenyl) phenoxy]ethyl} diethylamine | 911-45-5 | estrogen agonist | 7.2 | 9.31 | 139 | + | + | 12.86 |
| Clonidine | N-(2,6-dichlorophenyl)-4,5-dihydro-1H-imidazole-2-amine | 4205-90-7 | antihypertensive | 1.59 | 8.16 | 69.1 | - | - | ND |
| Cloricromen | 8-chloro-3-(2-diethylaminoethyl)-7-ethoxycarbonylmethoxy-4-methylcoumarin hydrochloride | 74697-28-2 | platelet aggregation inhibitor | 3.97 | 9.1 | 98.6 | - | + | 285 |
| Conessin | (3β)-N,N-dimethyl-con-5-enin-3-amine | 546-06-5 | antihistamine | 4.9 | 5 | 49 | - | - | 31.28 |
| Desloratadine | 13-chloro-2-(piperidin-4-ylidene)-4-azatricyclo [9.4.0.03,8] pentadeca-1(11),3(8),4,6,12,14-hexaene | 100643-71-8 | antihistamine | 3.48 | 9.73 | 107 | + | + | 8.36 |
| D-(+)-glucose | (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal | 50-99-7 | monosaccharide | -2.4 | -3 | 14.8 | - | - | ND |
| Diclofenac | (2-[(2,6-dichlorophenyl)amino] benzene acetic acid sodium salt-15307-79-6) | 15307-79-6 | nonsteroidal anti inflammatory | 4.51 | -2.1 | 20.3 | - | - | 7.2 |
| 5,7 Dichloro-8-hydroxy-2-methyl quinolone | 5,7-Dichloro-2-methyl-8-quinolinol | 72-80-0 | antioxidant | 3.61 | 4 | 29 | - | - | 1179 |
| Dilazep | 3-{4-[3-(3,4,5-trimethoxybenzoyloxy)propyl]-1,4-diazepan-1-yl} propyl 3,4,5-trimethoxybenzoate | 35898-87-4 | adenosine uptake inhibitor | 3.21 | 9.54 | 101 | + | + | 59.76 |
| 1,7-Dimethylxanthine | 1,7-Dimethyl-1H-purine-2,6-dione | 611-59-6 | stimulant | -0.8 | 13.5 | 183 | - | - | ND |
| Disopyramide | 4-[bis(propan-2-yl)amino]-2-phenyl-2-(pyridin-2-yl) butanamide | 3737-09-5 | antiarrhythmic | 2.58 | 10.31 | 115 | + | + | ND |
| Fenspiride | 8-(2-phenylethyl)-1-oxa-3,8-diazaspiro[4.5]decan-2-one | 5053-08-7 | anti-inflammatory | 1.81 | 9.37 | 91.1 | - | - | ND |
| Fosinopril | (2S,4S)-4-cyclohexyl-1-{2-[(R)-[(1S)-2-methyl-1-(propanoyloxy)propoxy](4-phenylbutyl) phosphoryl] acetyl} pyrrolidine-2-carboxylic acid | 98048-97-6 | Angiotensin-converting enzyme inhibitor | 5.62 | -4.4 | 31.6 | - | 0.181 | |
| Fosinoprilat | (2S,4S)-4-cyclohexyl-1-{2-[hydroxy(4-phenylbutyl)phosphoryl]acetyl}pyrrolidine-2-carboxylic acid | 95399-71-6 | active fosinopril metabolite | 3.7 | -4.7 | 35.8 | - | - | 5.764 |
| Fulvestrant | (1S,3aS,3bR,4R,9bS,11aS)-11a-methyl-4-[9-(4,4,5,5,5-pentafluoropentanesulfinyl)nonyl]-1H,2H,3H,3aH,3bH,4H,5H,9bH,10H,11H,11aH-cyclopenta[a]phenanthrene-1,7-diol | 129453-61-8 | chemotherapeutic | 6.54 | -0.88 | 42.8 | - | - | 61.85 |
| Fusidic acid | (3α,4α,5α,8α,9β,11α,13α,14, 16β,17Z)-16-acetoxy-3,11-dihydroxy-4,8,14-trimethyl-18-norcholesta-17,24-dien-21-oic acid | 6990-06-3 | antibiotic | 4.97 | -0.2 | 24.7 | - | - | 231 |
| Gabapentin | 2-[1-(amino methyl) cyclohexyl]acetic acid | 60142-96-3 | antiepileptic | -1.9 | 9.91 | 102 | - | - | 37.37 |
| Harmine | 7-methoxy-1-methyl-9H-pyrido[3,4-b]indole | 442-51-3 | central nervous system stimulant. | 2.61 | 6.46 | 48.5 | - | - | 633 |
| Hydralazine | 1-hydrazinylphthalazine | 86-54-4 | antihypertensive | 1 | 6.4 | 41 | - | - | 100 |
| Hydrocortisone | (11β)-11,17,21-trihydroxypregn-4-ene-3,20-dione | 50-23-7 | glucocorticoid | 1.61 | -2.8 | 10.4 | - | - | 402 |
| 6-Hydroxy-dopamine | 2,4,5-rihydroxyphenethylamine hydrochloride | 28094-15-7 | neurotoxin | 0.26 | 9.85 | 97.1 | - | - | 88.02 |
| 3-Hydroxy-tyramine hydrochloride | 2-(3,4-dihydroxyphenyl)ethylamine hydrochloride, 3,4-dihydroxyphenethylamine hydrochloride | 62-31-7 | catecholamine neurotransmitter | -0.91 | 9.27 | 86.9 | - | - | 56.08 |
| Imiquimod | 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine | 99011-02-6 | topical immunomodulatory | 2.83 | 5.01 | 33.1 | - | + | 160 |
| Isoxsuprine | 4-[(1S,2R)-1-hydroxy-2-{[(2R)-1-phenoxypropan-2-yl]amino}propyl]phenol | 395-28-8 | vasodilator | 2.06 | 9 | 85.2 | - | + | ND |
| Lidocaine | 2-diethylamino-N-(2,6-dimethylphenyl)acetamide | 137-58-6 | antiarrhythmic | 1.8 | 7.75 | 63.3 | - | - | ND |
| L-leucine | (2S)-2-amino-4-methylpentanoic acid | 61-90-5 | amino acid | -1.52 | 9.52 | 92.9 | - | - | ND |
| Mebhydrolin | 5-benzyl-2-methyl-1H,2H,3H,4H,5H-pyrido[4,3-b]indole | 524-81-2 | antihistamine | 3.5 | 6.7 | 57.1 | - | + | 146 |
| Meclofenamic acid | 2-[(2,6-dichloro-3-methylphenyl)amino]benzoic acid | 644-62-2 | nonsteroidal | 5.11 | -3.6 | 39.1 | - | - | ND |
| Melatonin | N-acetyl-5-methoxytryptamine | 73-31-4 | antigonadotrope | 1.42 | -1.6 | 4.6 | - | - | 38.03 |
| Mibefradil | (1S,2S)-2-(2-{[3-(1H-1,3-benzodiazol-2-yl)propyl] (methyl)amino}ethyl)-6-fluoro-1-(propan-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl 2-methoxyacetate | 116644-53-2 | calcium channel blocker | 5.34 | 9.82 | 124 | + | + | 12.92 |
| Naproxen | (2S)-2-(6-methoxynaphthalen-2-yl) propanoic acid | 22204-53-1 | nonsteroidal | 3.18 | -4.8 | 33.2 | - | - | 1102 |
| Orphenadrine | dimethyl({2-[(2-methylphenyl) (phenyl) methoxy] ethyl}) amine | 83-98-7 | muscle relaxant | 3.77 | 8.87 | 92.9 | + | + | 259.3 |
| Phenytoin | 5,5-diphenyl-2,4-imidazolidinedione, 5,5-Diphenylhydantoin sodium salt | 630-93-3 | anticonvulsant | 2.47 | -9 | 6.1 | - | - | 60.05 |
| Pipamperone | 1′-[4-(4-fluorophenyl)-4-oxobutyl]-[1,4′-bipiperidine]-4′-carboxamide | 1893-33-0 | antipsychotic | 2.32 | 8.96 | 85.7 | - | + | 250 |
| PP 06424439 | (3R)-1-[2-[1-(4-chloro-1H-pyrazol-1-yl)cyclopropyl]-3H-imidazo[4,5-b]pyridin-5-yl]-3-piperidinyl]-1-pyrrolidinyl-methanone | 1469284-79-4 | triglyceride and cholesterol lowering | 2.7 | 4.1 | 24.1 | - | - | 8217 |
| Prochlorperazine | 2-chloro-10-[3-(4-methylpiperazin-1-yl)propyl]-10H-phenothiazine | 58-38-8 | antipsychotic | 4.88 | 8.39 | 94.2 | + | + | 42.41 |
| Procyclidine | 1-cyclohexyl-1-phenyl-3-(pyrrolidin-1-yl)propan-1-ol | 77-37-2 | anticholinergic | 4.7 | 13.84 | 214 | + | + | 1470 |
| Ritanserin | 6-(2-{4-[bis(4-fluorophenyl)methylidene]piperidin-1-yl}ethyl)-7-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one | 87051-43-2 | serotonin receptor agonist | 5.02 | 8 | 89.2 | - | + | 13.39 |
| Rolipram | 4-[3-(cyclopentyloxy)-4-methoxyphenyl]pyrrolidin-2-one | 61413-54-5 | antidepressant | 2.15 | -1.9 | 9.9 | - | - | 300 |
| SB222200 | (S)-3-methyl-2-phenyl-N-(1-phenylpropyl)-4-quinolinecarboxamide-174635-69-9 | 174635-69-9 | antihistamine | 2.17 | 9.57 | 98.2 | + | + | 14.94 |
| S-methyl-isothiourea | methyl carbamimidothioate | 867-44-7 | iNOS inhibitor | 1.47 | 9.83 | 98.8 | - | - | ND |
| Suloctidil | (1R,2S)-2-(octylamino)-1-[4-(propan-2-ylsulfanyl)phenyl]propan-1-ol | 54767-75-8 | vasodilator | 5.54 | 9.76 | 126 | + | + | 6.82 |
| Trifluoperazine | 10-[3-(4-methylpiperazin-1-yl)propyl]-2-(trifluoromethyl) -10H-phenothiazine | 117-89-5 | antipsychotic, antiemetic | 4.87 | 8.39 | 94.1 | + | + | 6.87 |
| Uridine | 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl) oxolan-2-yl]-1,2,3,4-tetrahydropyrimidine-2,4-dione | 58-96-8 | pyrimidine analog | -1.98 | -3 | 3.9 | - | - | ND |
| Xylometazoline | 2-[(4-tert-butyl-2,6-dimethylphenyl)methyl]-4,5-dihydro-1H-imidazole | 526-36-3 | decongestant | 3.2 | 10.29 | 129 | + | + | 44.32 |
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 database 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. LPLA2 IC50 denotes the concentration at which 50% of the LPLA2 dependent 1-O-acyl N-acetylsphingosine synthase activity is observed.