Detailed information for compound 608049
Basic information
Technical information
- TDR Targets ID: 608049
- Name: N-(5-chloro-2,4-dimethoxyphenyl)-N-methyl-5,5 -dioxo-4H-thieno[4,5-c]thiochromene-2-carboxa mide
- MW: 463.954 | Formula: C21H18ClNO5S2
-
H donors: 0
H acceptors: 3
LogP: 4
Rotable bonds: 5
Rule of 5 violations (Lipinski): 1 - SMILES: COc1cc(OC)c(cc1N(C(=O)c1cc2c(s1)c1ccccc1S(=O)(=O)C2)C)Cl
- InChi: 1S/C21H18ClNO5S2/c1-23(15-9-14(22)16(27-2)10-17(15)28-3)21(24)18-8-12-11-30(25,26)19-7-5-4-6-13(19)20(12)29-18/h4-10H,11H2,1-3H3
- InChiKey: RXQJJBRAANNIDY-UHFFFAOYSA-N
Network
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Synonyms
- N-(5-chloro-2,4-dimethoxy-phenyl)-N-methyl-5,5-dioxo-4H-thieno[4,5-c]thiochromene-2-carboxamide
- N-(5-chloro-2,4-dimethoxy-phenyl)-5,5-diketo-N-methyl-4H-thieno[4,5-c]thiochromene-2-carboxamide
Targets
Known targets for this compound
| Species | Target name | Source | Bibliographic reference |
|---|---|---|---|
| Plasmodium falciparum | mitogen-activated protein kinase 2 | Starlite/ChEMBL | No references |
| Plasmodium falciparum | protein kinase 6 | Starlite/ChEMBL | No references |
| Plasmodium falciparum (isolate 3D7) | Calcium-dependent protein kinase 4 | Starlite/ChEMBL | No references |
| Plasmodium falciparum | lysine--tRNA ligase | Starlite/ChEMBL | No references |
| Plasmodium falciparum | hexose transporter | Starlite/ChEMBL | No references |
| Plasmodium falciparum | calcium-dependent protein kinase 1 | Starlite/ChEMBL | No references |
| Plasmodium falciparum (isolate 3D7) | Proline--tRNA ligase | Starlite/ChEMBL | No references |
| Homo sapiens | solute carrier family 2 (facilitated glucose transporter), member 1 | Starlite/ChEMBL | No references |
| Plasmodium falciparum | protein kinase 7 | Starlite/ChEMBL | No references |
| Leishmania mexicana | glucose transporter, lmgt2 | Starlite/ChEMBL | No references |
Predicted pathogen targets for this compound
By orthology
By sequence similarity to non orthologous known druggable targets
Obtained from network model
Ranking Plot
Putative Targets List
| Species | Potential target | Raw | Global | Species |
|---|---|---|---|---|
| Trichomonas vaginalis | purine nucleoside phosphorylase I, putative | 0.0136513 | 1 | 1 |
| Trypanosoma brucei | hypoxanthine-guanine phosphoribosyltransferase, putative | 0.00623108 | 0.119645 | 0.5 |
| Echinococcus multilocularis | purine nucleoside phosphorylase | 0.0136513 | 1 | 1 |
| Echinococcus granulosus | purine nucleoside phosphorylase | 0.0136513 | 1 | 1 |
| Leishmania major | xanthine phosphoribosyltransferase | 0.00623108 | 0.119645 | 0.5 |
| Schistosoma mansoni | purine nucleoside phosphorylase | 0.0136513 | 1 | 1 |
| Echinococcus multilocularis | purine nucleoside phosphorylase | 0.0106354 | 0.642183 | 0.593553 |
| Giardia lamblia | Purine nucleoside phosphorylase lateral transfer candidate | 0.0136513 | 1 | 1 |
| Mycobacterium leprae | Probable purine nucleoside phosphorylase DeoD (INOSINE PHOSPHORYLASE) (PNP) | 0.0136513 | 1 | 1 |
| Echinococcus multilocularis | purine nucleoside phosphorylase | 0.0136513 | 1 | 1 |
| Loa Loa (eye worm) | hypothetical protein | 0.0106354 | 0.642183 | 0.5 |
| Leishmania major | hypoxanthine-guanine phosphoribosyltransferase | 0.00623108 | 0.119645 | 0.5 |
| Echinococcus granulosus | purine nucleoside phosphorylase | 0.0136513 | 1 | 1 |
| Echinococcus multilocularis | purine nucleoside phosphorylase | 0.0136513 | 1 | 1 |
| Echinococcus granulosus | purine nucleoside phosphorylase | 0.0136513 | 1 | 1 |
| Echinococcus multilocularis | purine nucleoside phosphorylase | 0.0136513 | 1 | 1 |
| Echinococcus granulosus | purine nucleoside phosphorylase | 0.0136513 | 1 | 1 |
| Trypanosoma cruzi | hypoxanthine-guanine phosphoribosyltransferase, putative | 0.00623108 | 0.119645 | 0.5 |
| Schistosoma mansoni | purine nucleoside phosphorylase | 0.0136513 | 1 | 1 |
| Echinococcus multilocularis | purine nucleoside phosphorylase | 0.0136513 | 1 | 1 |
| Mycobacterium tuberculosis | Probable purine nucleoside phosphorylase DeoD (inosine phosphorylase) (PNP) | 0.0136513 | 1 | 1 |
| Trypanosoma cruzi | hypoxanthine-guanine phosphoribosyltransferase, putative | 0.00623108 | 0.119645 | 0.5 |
| Onchocerca volvulus | Purine nucleoside phosphorylase homolog | 0.0136513 | 1 | 1 |
| Plasmodium vivax | hypoxanthine-guanine phosphoribosyltransferase, putative | 0.00623108 | 0.119645 | 0.5 |
| Echinococcus granulosus | purine nucleoside phosphorylase | 0.0136513 | 1 | 1 |
| Echinococcus granulosus | purine nucleoside phosphorylase | 0.0136513 | 1 | 1 |
| Mycobacterium ulcerans | purine nucleoside phosphorylase | 0.0136513 | 1 | 1 |
| Toxoplasma gondii | hypoxanthine-xanthine-guanine phosphoribosyl transferase HXGPRT | 0.00623108 | 0.119645 | 0.5 |
| Trypanosoma cruzi | hypoxanthine-guanine phosphoribosyltransferase, putative | 0.00623108 | 0.119645 | 0.5 |
| Echinococcus multilocularis | purine nucleoside phosphorylase | 0.0136513 | 1 | 1 |
| Echinococcus granulosus | purine nucleoside phosphorylase | 0.0136513 | 1 | 1 |
| Trypanosoma cruzi | hypoxanthine-guanine phosphoribosyltransferase, putative | 0.00623108 | 0.119645 | 0.5 |
| Echinococcus granulosus | purine nucleoside phosphorylase | 0.0136513 | 1 | 1 |
| Plasmodium falciparum | hypoxanthine-guanine phosphoribosyltransferase | 0.00623108 | 0.119645 | 0.5 |
| Trypanosoma brucei | hypoxanthine-guanine phosphoribosyltransferase | 0.00623108 | 0.119645 | 0.5 |
| Echinococcus granulosus | inosine guanosine and xanthosine phosphorylase | 0.0106354 | 0.642183 | 0.593553 |
| Brugia malayi | purine nucleoside phosphorylase I, inosine and guanosine-specific family protein | 0.0136513 | 1 | 1 |
| Echinococcus multilocularis | purine nucleoside phosphorylase | 0.0106354 | 0.642183 | 0.593553 |
| Trypanosoma brucei | hypoxanthine-guanine phosphoribosyltransferase | 0.00623108 | 0.119645 | 0.5 |
Activities
| Activity type | Activity value | Assay description | Source | Reference |
|---|---|---|---|---|
| Activity (functional) | NOVARTIS: Antimalarial liver stage activity measured as a greater than 50% reduction in Plasmodium yoelii schizont area in HepG2-A16-CD81 cells at 10uM compound concentration, determined by immuno-fluorescence. | ChEMBL. | 22096101 | |
| CC50 (functional) | > 55.65 uM | Huh7 cytotoxicity for Pf inhibitors | Novartis-GNF Malaria Box. | No reference |
| CC50 | > 55.65 uM | NOVARTIS: Cytotoxicity against human hepatocellular carcinoma cell line (Huh7) | ChEMBL. | 18579783 |
| EC50 (functional) | = 78.2 nM | MMV: Inhibition of Plasmodium falciparum 3D7 (EC50). | ChEMBL. | No reference |
| EC50 (functional) | = 93.6 nM | MMV: Inhibition of Plasmodium falciparum K1 (EC50). | ChEMBL. | No reference |
| EC50 (functional) | = 0.113 uM | PF proliferation inhibition 3D7 | Novartis-GNF Malaria Box. | No reference |
| EC50 (functional) | = 0.113 uM | NOVARTIS: Inhibition of Plasmodium falciparum 3D7 (drug-susceptible) proliferation in erythrocyte-based infection assay | ChEMBL. | 18579783 |
| EC50 (functional) | = 0.1793 uM | W2 Pf proliferation inhibition | Novartis-GNF Malaria Box. | No reference |
| EC50 (functional) | = 0.1793 uM | NOVARTIS: Inhibition of Plasmodium falciparum W2 (drug-resistant) proliferation in erythrocyte-based infection assay | ChEMBL. | 18579783 |
| Growth Inhibition (functional) | = 6.301 % | MMV: Measure of pLDH activity as indication of parasite viability. Gametocytogenesis of 3D7 Plasmodium falciparum strain was induced in vitro and asexual parasites were depleted with N-acetylglucosamine. Gametocytes were treated with dihydroartemisinin, epoxomicin, methylene blue, primaquine, puromycin or chloroquine in 96-well plates and the pLDH activity was evaluated using a modified Makler protocol. Mosquito infectivity was measured by the standard membrane feeding assay. | ChEMBL. | No reference |
| IC50 (functional) | = 298.3 nM | MMV: IC50 determined against P. falciparum Dd2-luc strain using a Malaria Sybr Green I Fluorescence assay. Starting conditions were 1% trophozoite synchronised parasites at 2% haematocrit. Fluorescence detection completed after 48hr incubation at 37 degrees C under 1% O2, 3% CO2 and balance N2. | ChEMBL. | No reference |
| IC50 (functional) | > 12000 nM | ST_JUDE_LEISH: Cytotoxicity against transgenic Leishmania Mexicana promastigotes LmGT2 that are glucose transport deficient and complemented with the L. Mexicana glucose transporter 2. Activity is measured by by DNA content using SYBR green in vitro | ChEMBL. | No reference |
| IC50 (functional) | > 12000 nM | ST_JUDE_LEISH: Cytotoxicity against transgenic Leishmania Mexicana promastigotes LmGLUT1 that are glucose transport deficient and complemented with the human glucose transporter GLUT1. Activity is measured by DNA content using SYBR green in vitro | ChEMBL. | No reference |
| IC50 (functional) | > 12000 nM | ST_JUDE_LEISH: Cytotoxicity against transgenic Leishmania Mexicana promastigotes LmPfHT that are glucose transport deficient and complemented with the Plasmodium falciparum hexose transporter. Activity is measured by by DNA content using SYBR green in vitro | ChEMBL. | No reference |
| IC50 (functional) | > 0.5 uM | MMV: Modified 3H-Hyoxanthine uptake assay; RPMI 1640 (Invitrogen cat#23400-013) without Sodium Bicarbonate (NaHCO3). | ChEMBL. | No reference |
| IC50 (functional) | > 0.5 uM | MMV: 3H-Hyoxanthine uptake assay; RPMI 1640 (Invitrogen cat#11875-093) with Sodium Bicarbonate (NaHCO3) 2000 mg/mL. | ChEMBL. | No reference |
| IC50 (functional) | > 0.5 uM | MMV: 3H-Hyoxanthine uptake assay; 5% O2, 5% CO2 in N2. | ChEMBL. | No reference |
| IC50 (functional) | > 0.5 uM | MMV: Modified 3H-Hyoxanthine uptake assay; 1% O2, 5% CO2 in N2. | ChEMBL. | No reference |
| IC50 (functional) | > 1 uM | MMV: MAP2K Protein kinase inhibition assay using recombinant PfMAP2K, protein substrate, ATP and KinaseGlo to measure % inhibition at 1 uM MMV box compound. Final concentrations were 1 uM ATP, 0.5 mM DTT, 1 mM MgCl2, 0.5 mg/mL BSA, and 10 ug/ml MAP2 in a buffer of 50 mM HEPES (pH 7.0). 0.5 mg/mL histone III-S served as the substrate (13); 100 uM AMP-PNP, an ATP analog, was used as a control inhibitor. Incubation time was 4 hours. | ChEMBL. | No reference |
| IC50 (functional) | > 1 uM | MMV: CDPK1 Protein kinase inhibition assay using recombinant PfCDPK1, syntide 2 peptide substrate, ATP and KinaseGlo to measure % inhibition at 1 uM MMV box compound. | ChEMBL. | No reference |
| IC50 (functional) | > 1 uM | MMV: PK6 Protein kinase inhibition assay using recombinant PfPK6, Myelin Basic Protein (MBP) substrate, ATP and KinaseGlo to measure % inhibition at 1 uM MMV box compound. Final concentrations were 1.5 uM ATP, 5 mM MnCl2, and 15 ug/ml PK6 in a buffer of 100 mM Tris-HCl (pH 7.5). 50 ug/mL MBP was provided as the substrate; 10 uM staurosporine was used as a control inhibitor. Incubation time was 3 hours and 40 minutes.The catalytic activity of each kinase was considered proportional to ATP consumed, as determined from measurements of residual [ATP] with the luciferase-based reagent Kinase-Glo (Promega) following incubation. Luminescence (proportional to residual [ATP]) was measured on the plate readers FLx800 (BioTek Instruments, Winooski, VT, USA) and MicroBeta2. | ChEMBL. | No reference |
| IC50 (functional) | > 1 uM | MMV: CDPK4 Protein kinase inhibition assay using recombinant PfCDPK4, syntide2 peptide substrate, ATP and KinaseGlo to measure % inhibition at 1 uM MMV box compound. | ChEMBL. | No reference |
| IC50 (functional) | > 1 uM | MMV: PK7 Protein kinase inhibition assay using recombinant PfPK7, ATP and KinaseGlo to measure % inhibition at 1 uM MMV box compound. Final concentrations were 1 uM ATP, 2 mM DTT, 20 mM MgCl2, 2 mM MnCl2, 0.01% BSA, and 6 ug/ml PK7, in a buffer of 20 mM Tris-HCl (pH 7.5). The enzyme itself was the only substrate present (since autophosphorylation occurs); 100 uM 1NA-PP1 was used as a control inhibitor. Incubation time was 3 hours. | ChEMBL. | No reference |
| IC50 (functional) | > 2.5 uM | MMV: ProRS recombinant Plasmodium falciparum Prolyl-tRNA-synthetase, assay with yeast tRNA, ATP, and proline and 3 uM MMV malaria box compound, assay read out with kinase glo as % inhibition. | ChEMBL. | No reference |
| IC50 (functional) | > 2.5 uM | MMV: KRS recombinant Plasmodium falciparum Lysyl-tRNA-synthetase, assay with yeast tRNA, ATP, and lysine and 3 uM MMV malaria box compound, assay read out with kinase glo as % inhibition. | ChEMBL. | No reference |
| IC50 (functional) | = 4.35778665542603 uM | MMV: Inhibition of Trypanosoma brucei rhodesiense (STIB 900) (HAT in vitro). | ChEMBL. | No reference |
| IC50 (functional) | = 15.749921798706055 uM | MMV: Inhibition of Trypanosoma cruzi (Tulahuen C4 LacZ) (Chagas in vitro). | ChEMBL. | No reference |
| IC50 (functional) | = 15.7499217987061 uM | MMV: Inhibition of Trypanosoma cruzi (Tulahuen C4 LacZ) (Chagas in vitro). | ChEMBL. | No reference |
| IC50 (functional) | = 16.2279415130615 uM | MMV: Inhibition of Trypanosoma brucei brucei (Squib 427) (HAT in vitro). | ChEMBL. | No reference |
| IC50 (functional) | = 21.53440284729 uM | MMV: Inhibition of Leishmania infantum (MHOM/MA/BE/67) in vitro. | ChEMBL. | No reference |
| IC50 (functional) | = 21.53440284729004 uM | MMV: Inhibition of Leishmania infantum (MHOM/MA/BE/67) in vitro. | ChEMBL. | No reference |
| IC50 (functional) | > 30 uM | MMV: Primary screening was performed with each compound at a 30 uM final concentration and in triplicate in sealed 96-well polystyrene microtiter plates. Parasite inocula (100 ul) comprising 20000 parasites/ml were added to each well and grown at 37 degrees C in a humidified atmosphere of 5% CO2 for 72 h. Positive controls consisted of metronidazole at 1 mg/ml. The growth of E. histolytica trophozoites in each well was determined microscopically by measuring the diameters of the confluent cells in drug-containing wells relative to those in the nega- tive-control wells. | ChEMBL. | No reference |
| IC50 (functional) | > 30 uM | MMV: A total of 100ul of inoculum was added to each well (parasite/cell ratio, ~10:1; final volume, 200 ul). Six hours after inoculation, nonadherent parasites were removed, and 100 ul of complete DMEM (1% penicillin-streptomycin, 3% FBS) supplemented with inhibitors at different concentrations (2-fold serial dilutions starting from 30 uM) was added to all except the negative-control wells. Positive controls, consisting of pyrimethamine (PYR) and sulfadiazine (SDZ) (20-mg/ml stocks in DMSO), were tested at a 2mg/ml final concentration. Each test was performed in triplicate. | ChEMBL. | No reference |
| IC50 | > 32 uM | MMV: Cytotoxicity against human fibroblasts (MRC-5) cells. | ChEMBL. | No reference |
| IFI promiscuity index | = 0.02778 | IFI promiscuity index | Novartis-GNF Malaria Box. | No reference |
| Inhibition (functional) | = -25.679967297513308 % | MMV: Cryptosporidium parvum oocysts (Iowa Strain) were prepared for use by treatment with 10 mM HCl (37 degrees C, 10 min) followed by 2 mM sodium taurocholate in phosphate-buffered saline (PBS) with Ca2+ and Mg2+ (16 degrees C, 10 min) in order to stimulate excystation. The high-throughput screen was carried out by inoculating >90% confluent human ileocecal adenocarcinoma (HCT-8) cells (ATCC) with ~5.5 x 10^3 primed oocysts per well. Experimental compounds or DMSO (vehicle) were added three hours after infection, and cells were incubated for 48 hours. | ChEMBL. | No reference |
| Inhibition (functional) | = -25.6799672975133 % | MMV: Cryptosporidium parvum oocysts (Iowa Strain) were prepared for use by treatment with 10 mM HCl (37 degrees C, 10 min) followed by 2 mM sodium taurocholate in phosphate-buffered saline (PBS) with Ca2+ and Mg2+ (16 degrees C, 10 min) in order to stimulate excystation. The high-throughput screen was carried out by inoculating >90% confluent human ileocecal adenocarcinoma (HCT-8) cells (ATCC) with ~5.5 x 10^3 primed oocysts per well. Experimental compounds or DMSO (vehicle) were added three hours after infection, and cells were incubated for 48 hours. | ChEMBL. | No reference |
| Inhibition (functional) | = -16.250930504534416 % | MMV: P. berghei-infected blood was withdrawn from mice by cardiac pucture before being immediately added to ookinete culture medium containing test compounds. 26 hr later, GFP-positive ookinetes were identified and counted by automated microscopy. All compounds were tested in 4 independent experiments and data presented here is the mean. | ChEMBL. | No reference |
| Inhibition (functional) | = -16.2509305045344 % | MMV: P. berghei-infected blood was withdrawn from mice by cardiac pucture before being immediately added to ookinete culture medium containing test compounds. 26 hr later, GFP-positive ookinetes were identified and counted by automated microscopy. All compounds were tested in 4 independent experiments and data presented here is the mean. | ChEMBL. | No reference |
| Inhibition (functional) | = -14.8848786343722 % | MMV: P. falciparum NF54 functionally mature Stage V gametocytes were incubated for 24 hr in the presence of the test compounds. Gamete formation was then triggered by addition of 2uM xantheurenic acid and temperature decrease to ~20C. Female gamete formation was recorded 24 hr later by automated microscopy detection of surface labelling of female gametes with a Cy3-conjugated antibody reactive to Pfs25. All compounds were tested in 4 independent experiments and data presented here is the mean. | ChEMBL. | No reference |
| Inhibition (functional) | = 3 % | MMV: Malaria Box compounds were tested for inhibition of the human ether a go-go related gene (hERG), Kv11.1 channel, using IonWorks 384-well patch clamp electrophysiology at 1.1uM (3 independent assay plates up to 12 cells per concentration). | ChEMBL. | No reference |
| Inhibition (functional) | = 6.97 % | MMV: Screen against Mtb, single point, non replicating, at 25uM | ChEMBL. | No reference |
| Inhibition (functional) | = 7.68240494075156 % | MMV: P. falciparum NF54 functionally mature Stage V gametocytes were incubated for 24 hr in the presence of the test compounds. Gamete formation was then triggered by addition of 2uM xantheurenic acid and temperature decrease to ~20C. Male gamete exflagellation was recorded and analysed by automated microscopy after 20 min. All compounds were tested in 4 independent experiments and data presented here is the mean. | ChEMBL. | No reference |
| Inhibition (functional) | = 38 % | MMV: Screen against Mtb, single point, replicating, at 25uM | ChEMBL. | No reference |
| Inhibition (functional) | = 41 % | MMV: Malaria Box compounds were tested for inhibition of the human ether a go-go related gene (hERG), Kv11.1 channel, using IonWorks 384-well patch clamp electrophysiology at 11.1uM (3 independent assay plates up to 12 cells per concentration). | ChEMBL. | No reference |
| Inhibition (functional) | = 100 % | MMV: Inhibition of Plasmodium falciparum 3D7 at 5uM compound concentration. | ChEMBL. | No reference |
| IZ | = 0 mm | MMV: Selection for compounds that exhibit enhanced toxicity in combination with artemisinin. Assay utilized the disc diffusion method with the observance of a clear zone indicating inhibition of growth. Synthetic complete medium containing 3% glycerol as a carbon source (SCG) was used in each assay. 10 uL of each compound was added to a paper disc which was placed on SCG and SCG+Artemisinin (0.2 uM) plates seeded with 10e6 yeast cells (WC081 strain: Mat a, leu2 delta 0, lys2 delta 0, ura3 delta 0, his3 delta 1, pdr1 delta::HIS3, pdr3 delta::kanMX4, derived from BY4742, regulators of Multi-drug resistance transporters have been deleted to enhance toxicity of compounds). Plates were incubated at 30 degrees C for 5 days and clear zones were measured. Compounds that produced a larger clear zone in the presence of artemisinin was considered to have an additive interaction with artemisinin. Results are reported as diameter of clear zone on SCG+artemisinin plates - diameter of clear zone on SCG plates without artemisinin. | ChEMBL. | No reference |
| Potency (functional) | 20.5962 uM | PUBCHEM_BIOASSAY: Nrf2 qHTS screen for inhibitors. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID493153, AID493163, AID504648] | ChEMBL. | No reference |
| Ratio (functional) | = 1 | MMV: Compounds (1uM) were screened in a 72hr growth assay monitored by flow cytometry both in the presence and absence of supplemental isopentenyl pyrophosphate (IPP) 200uM. Compounds which fail to show anti-malarial activity when chemically rescued by IPP are therefore specific to the apicoplast. The values are expressed as the ratio of the corresponding activity with and without IPP, respectively. | ChEMBL. | No reference |
| Relative Growth (functional) | = -0.2428 | MMV: Growth assays were conducted using the prototrophic S. cerevisiae strain JHY222. Each MMV compound (0.1 mM) was tested in minimal media containing ethanol and glycerol as carbon sources (Yeast Nitrogen Base, Ethanol, Glycerol; YNBEG). The growth rate in the presence of each MMV compound was calculated as follows: (i) the first 10 OD readings were averaged and subtracted from all OD readings of the corresponding curve to set the baseline of the growth curve to zero, and (ii) the area under the curve (AUC) was then calculated as the sum of all OD readings. AUC was calculated following 180 OD readings, corresponding to roughly 45 h of growth. A relative growth value was calculated as follows: AUC(DRUG) - AUC(DMSO)/AUC(DMSO); where AUC(DMSO) represents growth measured in a DMSO control well that was on the same microtiter plate of the drug-treated culture. A relative growth value near zero means the compound had little or no effect on growth, whereas a value near -1 means the compound strongly or completely inhibited growth. | ChEMBL. | No reference |
| Relative Growth (functional) | = -0.2124 | MMV: Growth assays were conducted using the prototrophic S. cerevisiae strain JHY222. Each MMV compound (0.1 mM) was tested in rich media containing dextrose as a carbon source (Yeast Extract, Peptone, Dextrose; YPD). The growth rate in the presence of each MMV compound was calculated as follows: (i) the first 10 OD readings were averaged and subtracted from all OD readings of the corresponding curve to set the baseline of the growth curve to zero, and (ii) the area under the curve (AUC) was then calculated as the sum of all OD readings. AUC was calculated following 80 OD readings corresponding to roughly 20 h of growth. A relative growth value was calculated as follows: AUC(DRUG) - AUC(DMSO)/AUC(DMSO); where AUC(DMSO) represents growth measured in a DMSO control well that was on the same microtiter plate of the drug-treated culture. A relative growth value near zero means the compound had little or no effect on growth, whereas a value near -1 means the compound strongly or completely inhibited growth. | ChEMBL. | No reference |
| Relative Growth (functional) | = -0.1342 | MMV: Growth assays were conducted using the prototrophic S. cerevisiae strain JHY222. Each MMV compound (0.1 mM) was tested in minimal media containing dextrose as a carbon source (Yeast Nitrogen Base, Dextrose; YNBD). The growth rate in the presence of each MMV compound was calculated as follows: (i) the first 10 OD readings were averaged and subtracted from all OD readings of the corresponding curve to set the baseline of the growth curve to zero, and (ii) the area under the curve (AUC) was then calculated as the sum of all OD readings. AUC was calculated following 80 OD readings, corresponding to roughly 20 h of growth. A relative growth value was calculated as follows: AUC(DRUG) - AUC(DMSO)/AUC(DMSO); where AUC(DMSO) represents growth measured in a DMSO control well that was on the same microtiter plate of the drug-treated culture. A relative growth value near zero means the compound had little or no effect on growth, whereas a value near -1 means the compound strongly or completely inhibited growth. | ChEMBL. | No reference |
| Toxicity (functional) | = 0 | MMV: Toxicity @ 2.5 uM to newly transformed Schistosoma mansoni somules after 24 h on a scale of 0 (none) - 4 (most) as judged visually: includes short descriptors of effects (PMID:19597541). Caffrey group UCSF. | ChEMBL. | No reference |
| Toxicity (functional) | = 0 | MMV: Toxicity @ 2.5 uM to newly transformed Schistosoma mansoni somules after 72 h on a scale of 0 (none) - 4 (most) as judged visually: includes short descriptors of effects (PMID:19597541). Caffrey group UCSF. | ChEMBL. | No reference |
| Toxicity (functional) | = 0 | MMV: Toxicity @ 2.5 uM to newly transformed Schistosoma mansoni somules after 48 h on a scale of 0 (none) - 4 (most) as judged visually: includes short descriptors of effects (PMID:19597541). Caffrey group UCSF. | ChEMBL. | No reference |
Phenotypes
Whole-cell/tissue/organism interactions
| Species name | Source | Reference | Is orphan |
|---|---|---|---|
| Trypanosoma brucei gambiense | |||
| Plasmodium falciparum | ChEMBL23 | 18579783 | |
| Trypanosoma cruzi | ChEMBL23 |
Many chemical entities in TDR Targets come from high-throughput screenings with whole cells or tissue samples, and not all assayed compounds have been tested against a single a single target protein, probably because they get ruled out during screening process. Even if these compounds may have not been of interest in the original screening, they may come as interesting leads for other screening assays. Furthermore, we may be able to propose drug-target associations using chemical similarities and network patterns.
Annotated phenotypes:
We have no manually annotated phenotypes for this drug.
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In TDR Targets, information about phenotypes that are caused by
drugs, or by genetic manipulation of cells (e.g. gene knockouts or
knockdowns) is manually curated from the literature. These
descriptions help to describe the potential of the target for drug
development. If no information is available for this gene or if the
information is incomplete, this may mean that i) the papers
containing this information either appeared after the curation
effort for this organism was carried out or they were inadvertently
missed by curators; or that ii) the curation effort for this
organism has not yet started.
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External resources for this compound
- ChEMBL: CHEMBL585264
- Search by Novartis-GNF Malaria Box
Bibliographic References
No literature references available for this target.
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