In Silico Transcriptomic Analysis of Canadine Accumulation in Papaver Somniferum Cultivar
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Pharmacokinetic Interactions Between Herbal Medicines and Drugs: Their Mechanisms and Clinical Relevance
life Review Pharmacokinetic Interactions between Herbal Medicines and Drugs: Their Mechanisms and Clinical Relevance Laura Rombolà 1 , Damiana Scuteri 1,2 , Straface Marilisa 1, Chizuko Watanabe 3, Luigi Antonio Morrone 1, Giacinto Bagetta 1,2,* and Maria Tiziana Corasaniti 4 1 Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, Section of Preclinical and Translational Pharmacology, University of Calabria, 87036 Rende, Italy; [email protected] (L.R.); [email protected] (D.S.); [email protected] (S.M.); [email protected] (L.A.M.) 2 Pharmacotechnology Documentation and Transfer Unit, Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy 3 Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 981-8558 Sendai, Japan; [email protected] 4 School of Hospital Pharmacy, University “Magna Graecia” of Catanzaro and Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-0984-493462 Received: 28 May 2020; Accepted: 30 June 2020; Published: 4 July 2020 Abstract: The therapeutic efficacy of a drug or its unexpected unwanted side effects may depend on the concurrent use of a medicinal plant. In particular, constituents in the medicinal plant extracts may influence drug bioavailability, metabolism and half-life, leading to drug toxicity or failure to obtain a therapeutic response. This narrative review focuses on clinical studies improving knowledge on the ability of selected herbal medicines to influence the pharmacokinetics of co-administered drugs. Moreover, in vitro studies are useful to anticipate potential herbal medicine-drug interactions. -
“Biosynthesis of Morphine in Mammals”
“Biosynthesis of Morphine in Mammals” D i s s e r t a t i o n zur Erlangung des akademischen Grades Doctor rerum naturalium (Dr. rer. nat.) vorgelegt der Naturwissenschaftlichen Fakultät I Biowissenschaften der Martin-Luther-Universität Halle-Wittenberg von Frau Nadja Grobe geb. am 21.08.1981 in Querfurt Gutachter /in 1. 2. 3. Halle (Saale), Table of Contents I INTRODUCTION ........................................................................................................1 II MATERIAL & METHODS ........................................................................................ 10 1 Animal Tissue ....................................................................................................... 10 2 Chemicals and Enzymes ....................................................................................... 10 3 Bacteria and Vectors ............................................................................................ 10 4 Instruments ........................................................................................................... 11 5 Synthesis ................................................................................................................ 12 5.1 Preparation of DOPAL from Epinephrine (according to DUNCAN 1975) ................. 12 5.2 Synthesis of (R)-Norlaudanosoline*HBr ................................................................. 12 5.3 Synthesis of [7D]-Salutaridinol and [7D]-epi-Salutaridinol ..................................... 13 6 Application Experiments ..................................................................................... -
Coptis Japonica</Emphasis>
Plant Cell Reports (1988) 7:1-4 Plant Cell Reports © Springer-Verlag 1988 Alternative final steps in berberine biosynthesis in Coptisjaponica cell cultures E. Galneder 1 M. Rueffer 1, G. Wanner 1, 2, M. Tabata 1, 3, and M. H. Zenk 1 1 Lehrstuhl tar Pharmazeutische Biologie der Universitfit Mfinchen, Karlstrasse 29, D-8000 Mt~nchen 2, Federal Republic of Germany 2 Botanisches Institut der Universitfit Miinchen, Menzinger Strasse 67, D-8000 Manchen 19, Federal Republic of Germany 3 Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto 606, Japan Received October 30, 1987 - Communicated by K. Hahlbrock ABSTRACT oxidase (STOX) reported from our laboratory (Amann et al., 1984) in that the Coptis enzyme dehydrogenated In Coptis japonica cell cultures an alternative path- only (S)-canadine while other tetrahydroprotober- way has been discovered which leads from (S)-tetra- berines were reported to be inactive. In further hydrocolumbamine via (S)-canadine to berberine. The contrast to the STOX enzyme, their enzyme did not two enzymes involved have been partially purified. produce hydrogen peroxide but rather H20 as one of (S)-Tetrahydrocolumbamine is stereospecifically the reaction products. Our analysis of the Coptis transformed into (S)-canadine under formation of the system reported here led to the surprising result methylenedioxy bridge in ring A. This new enzyme was that the terminal two steps in the biosynthesis of named (S)-canad/ne synthase. (S)-Canadine in turn is berberine in 8erberis and Coptis are biochemically stereospecifically dehydrogenated to berberine by an completely different while similar at the cytological oxidase, (S)-canadine oxidase (COX), which was level. -
The Phytochemistry of Cherokee Aromatic Medicinal Plants
medicines Review The Phytochemistry of Cherokee Aromatic Medicinal Plants William N. Setzer 1,2 1 Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA; [email protected]; Tel.: +1-256-824-6519 2 Aromatic Plant Research Center, 230 N 1200 E, Suite 102, Lehi, UT 84043, USA Received: 25 October 2018; Accepted: 8 November 2018; Published: 12 November 2018 Abstract: Background: Native Americans have had a rich ethnobotanical heritage for treating diseases, ailments, and injuries. Cherokee traditional medicine has provided numerous aromatic and medicinal plants that not only were used by the Cherokee people, but were also adopted for use by European settlers in North America. Methods: The aim of this review was to examine the Cherokee ethnobotanical literature and the published phytochemical investigations on Cherokee medicinal plants and to correlate phytochemical constituents with traditional uses and biological activities. Results: Several Cherokee medicinal plants are still in use today as herbal medicines, including, for example, yarrow (Achillea millefolium), black cohosh (Cimicifuga racemosa), American ginseng (Panax quinquefolius), and blue skullcap (Scutellaria lateriflora). This review presents a summary of the traditional uses, phytochemical constituents, and biological activities of Cherokee aromatic and medicinal plants. Conclusions: The list is not complete, however, as there is still much work needed in phytochemical investigation and pharmacological evaluation of many traditional herbal medicines. Keywords: Cherokee; Native American; traditional herbal medicine; chemical constituents; pharmacology 1. Introduction Natural products have been an important source of medicinal agents throughout history and modern medicine continues to rely on traditional knowledge for treatment of human maladies [1]. Traditional medicines such as Traditional Chinese Medicine [2], Ayurvedic [3], and medicinal plants from Latin America [4] have proven to be rich resources of biologically active compounds and potential new drugs. -
Safrole and the Versatility of a Natural Biophore Lima, L
Artigo Safrole and the Versatility of a Natural Biophore Lima, L. M.* Rev. Virtual Quim., 2015, 7 (2), 495-538. Data de publicação na Web: 31 de dezembro de 2014 http://www.uff.br/rvq Safrol e a Versatilidade de um Biofóro Natural Resumo: Safrol (1) obtido de óleos essenciais de diferentes espécies vegetais tem ampla aplicação na indústria química como precursor sintético do butóxido de piperonila, piperonal e de fármacos como a tadalafila, cinoxacina e levodopa. Do ponto vista toxicológico, é considerado uma hepatotoxina por mecanismo de bioativação metabólica conduzindo a formação de intermediários eletrofílicos, e tem sido descrito como inibidor de diferentes isoenzimas da família CYP450. A versatilidade de sua estrutura, permitindo várias transformações químicas, e a natureza biofórica de sua unidade benzodioxola ou metilenodioxifenila conferem-lhe características singulares, que o tornam atrativo material de partida para a síntese de compostos com distintas atividades farmacológicas. Exemplos selecionados de compostos bioativos, naturais e sintéticos, contendo o sistema benzodioxola serão comentados, incluindo aqueles provenientes de contribuição específica do LASSBio®. Palavras-chave: Safrol; benzodioxola; metilenodioxi; CYP450; bióforo; compostos bioativos. Abstract Safrole (1), obtained from essential oils from different plant species, has wide application in the chemical industry as a synthetic precursor of piperonyl butoxide, piperonal and drugs such as tadalafil, cinoxacin and levodopa. From the toxicological point of view, it is considered a hepatotoxin through metabolic bioactivation, leading to the formation of electrophilic metabolites, and has been described as an inhibitor of different CYP450 isoenzymes. The versatility of its structure, allowing various chemical transformations, and the biophoric nature of its benzodioxole or methylenedioxy subunit, give it unique features and make it an attractive starting material for the synthesis of compounds with different pharmacological activities. -
Dr. Duke's Phytochemical and Ethnobotanical Databases Chemicals Found in Papaver Somniferum
Dr. Duke's Phytochemical and Ethnobotanical Databases Chemicals found in Papaver somniferum Activities Count Chemical Plant Part Low PPM High PPM StdDev Refernce Citation 0 (+)-LAUDANIDINE Fruit -- 0 (+)-RETICULINE Fruit -- 0 (+)-RETICULINE Latex Exudate -- 0 (-)-ALPHA-NARCOTINE Inflorescence -- 0 (-)-NARCOTOLINE Inflorescence -- 0 (-)-SCOULERINE Latex Exudate -- 0 (-)-SCOULERINE Plant -- 0 10-HYDROXYCODEINE Latex Exudate -- 0 10-NONACOSANOL Latex Exudate Chemical Constituents of Oriental Herbs (3 diff. books) 0 13-OXOCRYPTOPINE Plant -- 0 16-HYDROXYTHEBAINE Plant -- 0 20-HYDROXY- Fruit 36.0 -- TRICOSANYLCYCLOHEXA NE 0 4-HYDROXY-BENZOIC- Pericarp -- ACID 0 4-METHYL-NONACOSANE Fruit 3.2 -- 0 5'-O- Plant -- DEMETHYLNARCOTINE 0 5-HYDROXY-3,7- Latex Exudate -- DIMETHOXYPHENANTHRE NE 0 6- Plant -- ACTEONLYDIHYDROSANG UINARINE 0 6-METHYL-CODEINE Plant Father Nature's Farmacy: The aggregate of all these three-letter citations. 0 6-METHYL-CODEINE Fruit -- 0 ACONITASE Latex Exudate -- 32 AESCULETIN Pericarp -- 3 ALANINE Seed 11780.0 12637.0 0.5273634907250652 -- Activities Count Chemical Plant Part Low PPM High PPM StdDev Refernce Citation 0 ALKALOIDS Latex Exudate 50000.0 250000.0 ANON. 1948-1976. The Wealth of India raw materials. Publications and Information Directorate, CSIR, New Delhi. 11 volumes. 5 ALLOCRYPTOPINE Plant Father Nature's Farmacy: The aggregate of all these three-letter citations. 15 ALPHA-LINOLENIC-ACID Seed 1400.0 5564.0 -0.22115561650586155 -- 2 ALPHA-NARCOTINE Plant Jeffery B. Harborne and H. Baxter, eds. 1983. Phytochemical Dictionary. A Handbook of Bioactive Compounds from Plants. Taylor & Frost, London. 791 pp. 17 APOMORPHINE Plant Father Nature's Farmacy: The aggregate of all these three-letter citations. 0 APOREINE Fruit -- 0 ARABINOSE Fruit ANON. -
Appendix Human and Rat Liver Cytochromes P450: Functional
Appendix Human and Rat Liver Cytochromes P450: Functional Markers, Diagnostic Inhibitor Probes, and Parameters Frequently Used in P450 Studies Maria Almira Correia The tables in this appendix summarize the rel different P450 isoforms included in its evaluation ative functional selectivities of substrates and as well as the range of substrate/inhibitor concen inhibitors for the major human and rat liver trations tested. Second, substrates and inhibitors C3^ochrome P450 isoforms (P450s). These hepatic determined to be "relatively selective" for a human isoforms are well recognized to catalytically par liver isoform, may not necessarily be so for its rat ticipate in the metabolism of chemically diverse liver ortholog, and vice versa. Third, the relative endo- and xenobiotics including drugs, and in the metabolic contribution of a P450 isoform to the case of human liver P450s to thus contribute to in vivo hepatic metabolism of a given drug is directly clinically adverse drug-drug interactions. Conse proportional to the relative hepatic microsomal quently, these P450s are the targets of intense abundance of that isoform and its affinity for that scrutiny in the pharmaceutical screening of exist compound, irrespective of its in vitro high meta ing or novel chemical agents of potential clinical bolic profile assessed under "optimized" condi relevance for drug development. At a more basic tions. This issue arises because recent advances in level, these tables provide information on estab recombinant P450 technology have made unprece lished and/or potential diagnostic tools for the dented amounts of purified human liver enzymes identification and/or characterization of the meta readily available for comparative in vitro charac bolic role of each individual P450 in the disposition terization of drug metabolism, at relative P450 of an as yet uncharacterized xeno- or endobiotic. -
Dr. Duke's Phytochemical and Ethnobotanical Databases List of Chemicals for Chronic Venous Insufficiency/CVI
Dr. Duke's Phytochemical and Ethnobotanical Databases List of Chemicals for Chronic Venous Insufficiency/CVI Chemical Activity Count (+)-AROMOLINE 1 (+)-CATECHIN 5 (+)-GALLOCATECHIN 1 (+)-HERNANDEZINE 1 (+)-PRAERUPTORUM-A 1 (+)-SYRINGARESINOL 1 (+)-SYRINGARESINOL-DI-O-BETA-D-GLUCOSIDE 1 (-)-ACETOXYCOLLININ 1 (-)-APOGLAZIOVINE 1 (-)-BISPARTHENOLIDINE 1 (-)-BORNYL-CAFFEATE 1 (-)-BORNYL-FERULATE 1 (-)-BORNYL-P-COUMARATE 1 (-)-CANADINE 1 (-)-EPICATECHIN 4 (-)-EPICATECHIN-3-O-GALLATE 1 (-)-EPIGALLOCATECHIN 1 (-)-EPIGALLOCATECHIN-3-O-GALLATE 2 (-)-EPIGALLOCATECHIN-GALLATE 3 (-)-HYDROXYJASMONIC-ACID 1 (-)-N-(1'-DEOXY-1'-D-FRUCTOPYRANOSYL)-S-ALLYL-L-CYSTEINE-SULFOXIDE 1 (1'S)-1'-ACETOXYCHAVICOL-ACETATE 1 (2R)-(12Z,15Z)-2-HYDROXY-4-OXOHENEICOSA-12,15-DIEN-1-YL-ACETATE 1 (7R,10R)-CAROTA-1,4-DIENALDEHYDE 1 (E)-4-(3',4'-DIMETHOXYPHENYL)-BUT-3-EN-OL 1 1,2,6-TRI-O-GALLOYL-BETA-D-GLUCOSE 1 1,7-BIS(3,4-DIHYDROXYPHENYL)HEPTA-4E,6E-DIEN-3-ONE 1 Chemical Activity Count 1,7-BIS(4-HYDROXY-3-METHOXYPHENYL)-1,6-HEPTADIEN-3,5-DIONE 1 1,8-CINEOLE 1 1-(METHYLSULFINYL)-PROPYL-METHYL-DISULFIDE 1 1-ETHYL-BETA-CARBOLINE 1 1-O-(2,3,4-TRIHYDROXY-3-METHYL)-BUTYL-6-O-FERULOYL-BETA-D-GLUCOPYRANOSIDE 1 10-ACETOXY-8-HYDROXY-9-ISOBUTYLOXY-6-METHOXYTHYMOL 1 10-GINGEROL 1 12-(4'-METHOXYPHENYL)-DAURICINE 1 12-METHOXYDIHYDROCOSTULONIDE 1 13',II8-BIAPIGENIN 1 13-HYDROXYLUPANINE 1 14-ACETOXYCEDROL 1 14-O-ACETYL-ACOVENIDOSE-C 1 16-HYDROXY-4,4,10,13-TETRAMETHYL-17-(4-METHYL-PENTYL)-HEXADECAHYDRO- 1 CYCLOPENTA[A]PHENANTHREN-3-ONE 2,3,7-TRIHYDROXY-5-(3,4-DIHYDROXY-E-STYRYL)-6,7,8,9-TETRAHYDRO-5H- -
Pseudoxandra Sclerocarpa Maas, Colombian Medicinal Plant: a Review [Pseudoxandra Sclerocarpa Maas, Planta Medicinal Colombiana: Una Revisión]
Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas ISSN: 0717-7917 [email protected] Universidad de Santiago de Chile Chile Salazar, J. Rodrigo; Torres, Patrício; Serrato, Blanca; Dominguez, Mariana; Alarcón, Julio; Céspedes, Carlos L. Insect Growth Regulator (IGR) effects of Eucalyptus citriodora Hook (Myrtaceae) Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas, vol. 14, núm. 5, 2015, pp. 403-422 Universidad de Santiago de Chile Santiago, Chile Available in: http://www.redalyc.org/articulo.oa?id=85641105006 How to cite Complete issue Scientific Information System More information about this article Network of Scientific Journals from Latin America, the Caribbean, Spain and Portugal Journal's homepage in redalyc.org Non-profit academic project, developed under the open access initiative © 2015 Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas 14 (4): 308 – 316 ISSN 0717 7917 www.blacpma.usach.cl Revisión | Review Pseudoxandra sclerocarpa Maas, Colombian medicinal plant: a review [Pseudoxandra sclerocarpa Maas, planta medicinal colombiana: una revisión] Jazmin Prieto1, Diego Cortes2, Luisauris Jaimes3, Claudio Laurido4, Raul Vinet5 & José L. Martínez6 1Universidad Nacional de Colombia, sede Palmira 2Facultad de Farmacia, Universidad de Valencia, España 3Facultad de Ciencias de la Educación, Universidad de Carabobo, Valencia, Venezuela 4Facultad de Química y Biología, Universidad de Santiago de Chile 5Facultad de Farmacia, Universidad de Valparaíso, and Centro Regional de Estudios en Alimentos Saludables, Valparaíso, Chile 6Vicerrectoría de Investigación, Desarrollo e Innovación, Universidad de Santiago de Chile Contactos | Contacts: José L. MARTÍNEZ - E-mail address: [email protected] Abstract: The Annonaceae family is one of the largest, with 130 genre and 2500 species, consisting of trees, shrubs and a few vines. -
Proquest Dissertations
u Ottawa l.'Univcrsilc cnnndicnnc C.'inadn's linivcrsily FACULTE DES ETUDES SUPERIEURES l==l FACULTY OF GRADUATE AND ET POSTOCTORALES U Ottawa POSDOCTORAL STUDIES L'UniversitG canadienne Canada's university Renee Leduc TOTEURWEniS'SErAUTHOROrfHESiS" M.Sc. (Biology) GRADE/DEGREE Department of Biology "F7CUITOC6LTD!PARTE¥OT^^ Phytochemical Variation in Canadian Hydrastis canadensis L. (Goldenseal) and the In vitro Inhibition of Human Cytochrome P450-mediated Drug Metabolism by H. canadensis and Other Botanicals TITRE DE LA THESE / TITLE OF THESIS Dr. John T. Amason TJiRECTEURpRiC^ Dr. Robin J. Maries CO-DIRECTEUR"(CO-DIRECfRICE) DE LATHISE / THl¥s"CO^"UPERVlSOR EXAMINATEURS (EXAMINATRICES) DE LA THESE / THESIS EXAMINERS Dr. Jeremy Kerr Dr. Paul Caitling Dr. Naomi Cappuccino Gary W. Slater Le Doyen de la Faculte des etudes superieures et postdoctorales / Dean of the Faculty of Graduate and Postdoctoral Studies PHYTOCHEMICAL VARIATION IN CANADIAN HYDRASTIS CANADENSIS L. (GOLDENSEAL) AND THE IN VITRO INHIBITION OF HUMAN CYTOCHROME P450-MEDIATED DRUG METABOLISM BY H. CANADENSIS AND OTHER BOTANICALS RENEEIRENE LEDUC Thesis submitted to the Faculty of Graduate and Postdoctoral Studies University of Ottawa in partial fulfillment of the requirements for the M.Sc. degree in the Ottawa-Carleton Institute of Biology These soumise a Faculte des etudes superieures et postdoctorales Universite d'Ottawa en vue de I'obtention de la maitrise es sciences L'lnstitut de biologie d'Ottawa-Carleton © Renee I. Leduc, Ottawa, Canada, 2007 Library and Bibliotheque -
Dr. Duke's Phytochemical and Ethnobotanical Databases List of Chemicals for Tinnitus
Dr. Duke's Phytochemical and Ethnobotanical Databases List of Chemicals for Tinnitus Chemical Activity Count (+)-ALPHA-VINIFERIN 1 (+)-AROMOLINE 1 (+)-BORNYL-ISOVALERATE 1 (+)-CATECHIN 1 (+)-EUDESMA-4(14),7(11)-DIENE-3-ONE 1 (+)-HERNANDEZINE 2 (+)-ISOLARICIRESINOL 1 (+)-NORTRACHELOGENIN 1 (+)-PSEUDOEPHEDRINE 1 (+)-SYRINGARESINOL-DI-O-BETA-D-GLUCOSIDE 1 (+)-T-CADINOL 1 (-)-16,17-DIHYDROXY-16BETA-KAURAN-19-OIC 1 (-)-ALPHA-BISABOLOL 1 (-)-ANABASINE 1 (-)-APOGLAZIOVINE 1 (-)-BETONICINE 1 (-)-BORNYL-CAFFEATE 1 (-)-BORNYL-FERULATE 1 (-)-BORNYL-P-COUMARATE 1 (-)-CANADINE 1 (-)-DICENTRINE 1 (-)-EPICATECHIN 2 (-)-EPIGALLOCATECHIN-GALLATE 1 (1'S)-1'-ACETOXYCHAVICOL-ACETATE 1 (E)-4-(3',4'-DIMETHOXYPHENYL)-BUT-3-EN-OL 1 1,7-BIS-(4-HYDROXYPHENYL)-1,4,6-HEPTATRIEN-3-ONE 1 1,8-CINEOLE 4 Chemical Activity Count 1-ETHYL-BETA-CARBOLINE 2 10-ACETOXY-8-HYDROXY-9-ISOBUTYLOXY-6-METHOXYTHYMOL 1 10-DEHYDROGINGERDIONE 1 10-GINGERDIONE 1 12-(4'-METHOXYPHENYL)-DAURICINE 1 12-METHOXYDIHYDROCOSTULONIDE 1 13',II8-BIAPIGENIN 1 13-HYDROXYLUPANINE 1 13-OXYINGENOL-ESTER 1 16,17-DIHYDROXY-16BETA-KAURAN-19-OIC 1 16-HYDROXY-4,4,10,13-TETRAMETHYL-17-(4-METHYL-PENTYL)-HEXADECAHYDRO- 1 CYCLOPENTA[A]PHENANTHREN-3-ONE 16-HYDROXYINGENOL-ESTER 1 2'-O-GLYCOSYLVITEXIN 1 2-BETA,3BETA-27-TRIHYDROXYOLEAN-12-ENE-23,28-DICARBOXYLIC-ACID 1 2-METHYLBUT-3-ENE-2-OL 2 2-VINYL-4H-1,3-DITHIIN 1 20-DEOXYINGENOL-ESTER 1 22BETA-ESCIN 1 24-METHYLENE-CYCLOARTANOL 2 3,3'-DIMETHYLELLAGIC-ACID 1 3,4-DIMETHOXYTOLUENE 2 3,4-METHYLENE-DIOXYCINNAMIC-ACID-BORNYL-ESTER 1 3,4-SECOTRITERPENE-ACID-20-EPI-KOETJAPIC-ACID -
A Computational Tool for Pathway-Based Rational Drug Repositioning Supplementary Information
gene2drug: a Computational Tool for Pathway-based Rational Drug Repositioning Supplementary Information Francesco Napolitano1, Diego Carrella1, Barbara Mandriani1, Sandra Pisonero1, Diego Medina1, Nicola Brunetti-Pierri1,2, and Diego di Bernardo1,3 1Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli (NA), 80078, Italy. 2Department of Translational Medicine, Federico II University, 80131 Naples, Italy 3Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, 80125 Naples, Italy. List of Figures S1 Relation between PPI network-based and pathway based approaches. Given a therapeutic gene and the set of pathways it is annotated to according to the different databases, the other genes in the same pathways are topologically closer to it in the PPI network as compared to randomly chosen genes. The average shortest path from the selected gene to other pathway members is reported on the y axis for each database. 3 S2 Size of intersection between existent evidence scores in the STITCH database (subset matched against the Cmap database) as a percentage of the total number of evidences. Numbers on the diagonal represent how many times a drug-target evidence exists divided by the total number of reported pairs. A \combined score" always exist if one of the other evidences exist, thus \combined score" covers 100% of the pairs. Conversely, an \experimental" score is only present for 14% of the pairs. The \Text mining" evidence strongly drives the \combined score" covering 61% of all the known protein-target interactions in STITCH. 4 S3 Relative luminescence units (RLU) in Hepa1-6 cells transfected with a plasmid ex- pressing the luciferase gene under the control of the GPT promoter and incubated with various concentrations of fulvestrant.