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Table S2  Phenotypes recorded against S. mansoni adults at 1 µM in vitro with those hit compounds that arose in screens against schistosomula | Unnamed: 1 | Unnamed: 2 | Unnamed: 3 | Unnamed: 4 | Unnamed: 5
[NAME] | HIT and phenotype or NO HITa | 50% [NAME] (LD50) of hit compound, if availableb | Therapy/Target (if known) | Hit Compound Availability | GO / NO GO  to animal model based on speed of phenotype appearance, phenotype severity, and available LD50 and clinical data
2,3,29-triacetoxy-24-nor-1,3,5,7-friedelatetraene | HIT: Slow after 7 h progressing to slow, dark, sexes separate after 24 h; dying by 4 d (1/2) |  |  |  | NO GO at this time: chemically related to celastrol but with weaker phenotype
Alexidine hydrochloride | NO HIT (2/2) |  |  |  | NO GO
Amitriptyline hydrochloride | NO HIT (2/2) |  |  |  | NO GO
Amphotericin b | NO HIT (2/2) |  |  |  | NO GO
[NAME] | HIT: on sides after 24 h progressing to dark, on sides by 3 d (2/2) | LD50 (oral-mouse): 148 mg/kg; LD50 (IP-mouse): 400 mg/kg | Antibiotic produced by Streptomyces griseolus | Various  vendors | GO
Benztropine mesylate | NO HIT (2/2) |  |  |  | NO GO
Bithionol | HIT:  [NAME], on sides after 24 h progressing to slow, dark, on sides by 3 d (2/2) | LD50 (oral-mouse): 760 mg/kg; LD50 (IP-mouse): 100 mg/kg | Known flukicide. No apparent effect on schistosome egg counts in patients (Farag et al., 1988. Am. [NAME]. Med. Hyg. 91:240) | Sigma-Aldrich | NO GO at this time: literature suggests lack of efficacy
Celastrol | HIT:  slow, dark shrunken by 24 h progressing to slow, dark, death by 48 h (2/2) | For celastrol-methylether: LD50 (oral-mouse): 8 g/kg; LD50 (IP-mouse): 200 mg/kg; no effect to mice after  3 mg/kg p.o. ([NAME], 2001; Prog Neuropsychopharmacol Biol Psychiatry. 25:1341) | Antioxidant, anti-inflammatory, possible treatment for neurodegenerative disease; a quinone methide triterpene derived from the medicinal plant Tripterygium wilfordii | http://www.gaiachem.com/prods.html | NO GO: death of mice within one day of a single 10 mg/ kg i.p. dose (R. Swenerton, unpubl.)
Chlorpromazine hydrochloride | HIT: Overactive after 7 h without progression (2/2) | LD50 (oral -rat): 225mg/kg; LD50 (oral -rat):141 mg/kg;  LD50 (oral - mouse): 135mg/kg;  LD50 (oral - mouse): 376mg/kg | Treatment of schizophrenia, control nausea and vomiting;  a sedative; controls the manifestations of manic depression. | Various  vendors | NO GO at this time: lacks a death phenotype outcome in addition to likely CNS effects
[NAME] hydrochloride | WEAK HIT: Transient overactivity  up to 24 h (2/2) |  |  |  | NO GO
Clofoctol | NO HIT (2/2) |  |  |  | NO GO
[NAME] citrate | NO HIT (1/1) |  |  |  | NO GO
Clomipramine hydrochloride | WEAK HIT: Transient overactivity up to 24 h (1/2) |  |  |  | NO GO
Cyclobenzaprine hydrochloride | WEAK HIT: Transient overactivity up to 24 h (1/2) |  |  |  | NO GO
Cyclosporin A | STRONG HIT: Overactive after 7 h progressing to slow on sides by 3 d (1/2) | LD50 (oral-mouse): 2329 mg/kg; LD50 (IP-rat): 147 mg/kg | Known anthelmintic/schistosomicide/anti-protozoal. An immunesuppressant. | http://www.rspharmchem.com/cyclosporin-a.htm | NO GO: an immunosuppressant
Cytochalasin q | NO HIT (2/2) |  |  |  | NO GO
[NAME] acid | STRONG HIT: Slow, dark, on sides after 7 h progressing to death by 3 d (2/2) | LD50 (oral-mouse): 962 mg/kg | [NAME] (Usnea spp.) | http://www.gaiachem.com/prods.html | GO
Digitonin | HIT: Slow, dark after 24 h without progression (1/2) | LD50 (oral-mouse): 90 mg/kg; LD10 (IP-mouse): 20 mg/kg | A glycoside obtained from Digitalis purpurea; used as a detergent to solubilizes lipids; mutagen . | Various  vendors | NO GO: a mutagen
Dihydrocelastryl diacetate | HIT: sexes separate, dark after 24 h progressing to slow, dying after 3 d (2/2) |  | Related to Celastrol |  | NO GO:  chemically related to celastrol which is toxic
Dihydrogambogic acid | HIT: slow, on sides after 3 d (1/2) |  | A xanthone derived from the resin of the Garcinia hanburyi | http://www.gaiachem.com/prods.html | NO GO: chemically related to gambogic acid, but with a weaker phenotype
Dihydrorotenone | NO HIT (2/2) |  |  |  | NO GO
[NAME] hydrochloride | HIT: Overactive after 7 h without progression (2/2) | LD50 (oral-mouse): 180 mg/kg; LD50 (IP-mouse): 79 mg/kg | A tricyclic antidepressant of the dibenzazpine type to treat depression,  anxiety and, topically, pruritus associated with eczema. | Various  vendors | NO GO: chemically related to imipramine but with a lower LD50
Dyclonine hydrochloride | NO HIT (1/1) |  |  |  | NO GO
Epoxygedunin | NO HIT (1/1) |  |  |  | NO GO
Ergonovine maleate | NO HIT (1/1) |  |  |  | NO GO
Ethinyl estradiol | HIT:  Overactive after 24 h progressing  to dark, slow by 4 d (1/2) | LD50 (oral-mouse): 950 mg/kg; LD50 (IP-mouse): 250 mg/kg | Treatment of  vasomotor symptoms associated with  menopause, female hypogonadism, prostatic carcinoma-palliative therapy of advanced disease, breast cancer, oral contraceptive, and emergency contraceptive. | http://www.caymanchem.com/ | NO GO : a hormone
Fluoxetine hydrochloride | WEAK HIT: Transient overactivity up tp 24 h (2/2) |  |  |  | NO GO
Gambogic acid | STRONG HIT: Slow, on sides by 7 h progressing to slow, dark on sides, shrunken by 24 h and dying by 4 d (2/2) | LD50 (IV- mouse): 43 - 48 mg/kg (Gou et al., 2006). Basic & Clinical Pharmacology & Toxicology 2006, 99, 178–184.   LD50 (subcut-mouse): 354 mg/kg; LD50 (IP-rat): 88 mg/kg | Xanthone derived from the resin of the Garcinia hanburyi | http://www.gaiachem.com/prods.html | GO
Gramicidin | NO HIT (2/2) |  |  |  | NO GO
Hycanthone | HIT: on sides, slow after 48 h progressing to shrunken, dying by 4 d (2/2) | LD50 (oral-mouse): 1120 mg/kg; LD50 (subcut-mouse): 270 mg/kg | Thioxanthene derivative of lucanthone with anti-schistosomal activity and potential antineoplastic activity; Effective against S. mansoni and S. haematobium; Ineffective against S. japonicum. Hepatotoxic. | Sigma-Aldrich | NO GO: former drug therapy but hepatotoxic
Imipramine hydrochloride | HIT: Overactive after 7 h without progression (2/2) | LD50 (oral-mouse): 275 mg/kg; LD50 (IP-mouse): 104 mg/kg | Trucyclic antidepressant of the dibenzazapine class,  Norepinephrine-Reuptake Inhibitor; Adrenergic Uptake Inhibitor | Sigma-Aldrich | NO GO at this time: possible CNS effects
Isorotenone | NO HIT (2/2) |  |  |  | NO GO
Lasalocid sodium | STRONG HIT:  [NAME], dark, on sides after 7 h  progressing to dying, teg. blebs by 4 d (2/2) | LD50 (oral -mouse): 146 mg/kg;  LD50 (IP-mouse): 64 mg/kg | Cationic ionophore antibiotic  from Streptomyces lasaliensis that, among other effects, dissociates the calcium fluxes in muscle fibers.  A coccidiostat, especially in poultry. | Obtained upon specific request from Alpharma Inc. | GO
Methomyl | NO HIT (1/1) |  |  |  | NO GO
Miconazole nitrate | NO HIT (1/1) |  |  |  | NO GO
Monensin sodium (monensin a is shown) | HIT: Slow, on sides after 48 h without progression (1/2) | LD50 (oral-mouse): 44 mg/kg; TDLo (oral-mouse): 409 mg/kg/13W-C | Ionophore used as antiprotozoal, antibacterial, antifungal | Calbiochem,  [NAME] | NO GO: chemically related to lasalocid with lower IP LD50
Neostigmine bromide | NO HIT (2/2) |  |  |  | NO GO
Niclosamide | STRONG HIT: Slow, shrunken  after 7 h progressing to dying, teg. blebs by 2 d (2/2) | LD50 (oral-mouse): 1500 mg/kg; LD50 (IP-mouse): 210 mg/kg ([NAME] et al., 1983; Pharmac. Ther. 19:245) | Known anthelmintic/molluscicide. Prevents penetration of schistosome cercariae. | Sigma-Aldrich | GO: however, limited oral bioavailability
Nigericin sodium | HIT: Slow, on sides after 24 h progressing to slow, dark, shrunken by 3 d (2/2) | LD50 (IP-mouse): 48 mg/kg | An antibiotic derived from Streptomyces hygroscopicus; | Sigma-Aldrich | NO GO: chemically related to lasalocid but with a lower oral LD50
Perseitol | NO HIT (1/1) |  |  |  | NO GO
(-)-Physostigmine | NO HIT (2/2) |  |  |  | NO GO
Praziquantel | STRONG HIT: Extremely shrunken, dark, slow, tegumental blebs by 7 h progressing to dying by 48 h (2/2) | LD50 (oral-mouse): 2454 mg/kg; LD50 (IP-mouse): 376 mg/kg | Known anthelmintic and current therapy for schistosomiasis | Various  vendors | CURRENT DRUG THERAPY: used as 'gold standard' drug in infected mice
[NAME] hydrochloride | NO HIT (1/1) |  |  |  | NO GO
Promazine hydrochloride | HIT: Overactive after 7 h without progression (2/2) | LD50 (subcut-mouse): 300 mg/kg; LD50 (IM-mouse): 28 mg/kg; LD50 (oral-rat): 400 mg/kg; LDLo (IP-rat): 356 mg/kg | A phenothiazine with antipsychotic, antiemetic; neuroleptic effects. Action similar to chlorpromazine w/ less antipsychotic activity; | Sigma-Aldrich | NO GO at this time: lacks a death phenotype outcome in addition to likely CNS complications
Pyrromycin | NO HIT (1/1) |  |  |  | NO GO
Pyrvinium pamoate | HIT:  Teg bleb by 24 h progressing to death by 4 d (2/2) |  | A  gastro-intestinal anthelmintic | Sigma-Aldrich | NO GO at this time: does not cross GI tract
[NAME] b | STRONG HIT:  [NAME], dark, slow after 7 h progressing to teg. blebs and death by 24 h (2/2) |  | Antibacterial, cytotoxic activity; from bark extract of Pilidiostigma tropicum ([NAME]) from north Queensland, Australia.  Low micromolar (2 - 30 µM) in vitro LD50 values  against human hepatocellular carcinoma and mammary adenocarcinoma cell lines ([NAME] et al., [NAME] (2006) 12:703.) | http://www.gaiachem.com/prods.html | NO GO at this time: toxicity suggested
Ribostamycin sulfate | NO HIT (2/2) |  |  |  | NO GO
Salinomycin, sodium | HIT:  [NAME], on sides after 24 h progressing  to slow, dark, on sides by 4 d (1/2) | LD50 (oral-mouse): 500 mg/kg; LD50 (IP-mouse): 25 mg/kg | Prevention of coccidiosis in broiler chickens | Sigma-Aldrich | NO GO: chemically related to lasalocid with but a lower i.p. LD50
Sanguinarine chloride | NO HIT (2/2) |  |  |  | NO GO
Sisomicin sulfate | NO HIT (1/1) |  |  |  | NO GO
Taxol | NO HIT (2/2) |  |  |  | NO GO
[NAME] | NO HIT (2/2) |  |  |  | NO GO
Tomatine | NO HIT (2/2) |  |  |  | NO GO
Triflupromazine hydrochloride | WEAK HIT: Transient overactivity up to 24 h(1/2) |  |  |  | NO GO
Triptonide | Hit: Slow after 24 h progressing to slow, dark, on sides by 3 d (1/2) |  | Anti-spermatogenic (male antifertility drug); isolated from multiglycosides of Tripterygium wilfordii; immunosuppressive |  | NO GO at this time:  based on properties
(±)-Verapamil hydrochloride | NO HIT (1/1) |  |  |  | NO GO
a  Brackets indicate the number of experiments  performed for each compound. |  |  |  |  | 5 compounds prioritized for efficacy tests in murine model.
b LD50 data  are variously available from http://www.inchem.org/,  http://hazard.com/,  http://www.drugbank.ca/ or as otherwise stated.