TY - JOUR
AU - Chen, Y. Z.
AB - Abstract A number of proteins and nucleic acids have been explored as therapeutic targets. These targets are subjects of interest in different areas of biomedical and pharmaceutical research and in the development and evaluation of bioinformatics, molecular modeling, computer-aided drug design and analytical tools. A publicly accessible database that provides comprehensive information about these targets is therefore helpful to the relevant communities. The Therapeutic Target Database (TTD) is designed to provide information about the known therapeutic protein and nucleic acid targets described in the literature, the targeted disease conditions, the pathway information and the corresponding drugs/ligands directed at each of these targets. Cross-links to other databases are also introduced to facilitate the access of information about the sequence, 3D structure, function, nomenclature, drug/ligand binding properties, drug usage and effects, and related literature for each target. This database can be accessed at http://xin.cz3.nus.edu.sg/group/ttd/ttd.asp and it currently contains entries for 433 targets covering 125 disease conditions along with 809 drugs/ligands directed at each of these targets. Each entry can be retrieved through multiple methods including target name, disease name, drug/ligand name, drug/ligand function and drug therapeutic classification. Received July 23, 2001; Revised and Accepted August 28, 2001. INTRODUCTION Pharmaceutical agents generally exert their therapeutic effect by binding to a particular protein or nucleic acid target (1,2). So far, hundreds of proteins and nucleic acids have been explored as therapeutic targets (1). Rapid advances in genetic (3), structural (4) and functional (5) information of disease related genes and proteins not only raise strong interest in the search of new therapeutic targets, but also promote the study of various aspects of known targets including molecular mechanism of their binding agents and related adverse effects (6), and pharmacogenetic implications of sequence or proteomic variations (7), etc. The knowledge gained from such a study is important in facilitating the design of more potent, less toxic and personalized drugs. Development of advanced computational methods for bioinformatics (4), molecular modeling (8), drug design and pharmacokinetics analysis (9–11) increasingly uses known therapeutic targets to refine and test algorithms and parameters. A publicly accessible database that provides comprehensive information about these targets is therefore helpful in catering for the need and interest of the relevant communities in general and those unfamiliar with a specific therapeutic target in particular. To the best of the authors’ knowledge, such a publicly accessible database is not yet available. In this work, we introduce a Therapeutic Target Database (TTD), which contains information about the known therapeutic protein and nucleic acid targets together with the targeted disease conditions, the pathway information and the corresponding drugs/ligands directed at each of these targets. Cross-links to other databases are introduced to facilitate the access of information regarding the function, sequence, 3D structure, nomenclature, drug/ligand binding properties and related literatures of each target. The therapeutic targets collected in TTD are from a search of the available literature. It has been reported that, at present, approximately 500 therapeutic targets have been exploited in the currently available medical treatment (1). An effort has been made to collect as many of these known targets as possible. However, description of some of these targets in the literature was not specific enough to point to a particular protein or nucleic acid as the target. Hence these targets are not included in our database. DATABASE STRUCTURE AND ACCESS TTD has a web interface at http://xin.cz3.nus.edu.sg/Group/ttd/ttd.asp. The entries of this database are generated from a search of pharmacology textbooks (12,13), review articles (14–21) and a number of recent publications. Our database currently contains 433 entries of protein and nucleic acid targets found from the literature. These targets cover 125 different disease conditions, which are described in the database. Drugs and ligands directed at each of these targets are searched and included in the database. A total of 809 different drugs and ligands are listed in the database. The TTD database web interface is shown in Figure 1. This database is searchable by target name or drug/ligand name. It can also be accessed by selection of disease name, drug/ligand function or drug therapeutic classification from the list provided in the corresponding selection field. Searches involving any combination of these five search or selection fields are also supported. The lists of disease names, drug/ligand functions and drug classifications are given in Tables 1, 2 and 3, respectively. The search is case insensitive. In a query, a user can specify full name or any part of the name in a text field, or choose one item from a selection field. Wild characters of ‘%’ and ‘_’ are supported in text field. Here, ‘_’ represents any one character and ‘%’ represents a string of characters of any length. For example, input of ‘phosphatase’ in the target name field finds entries containing ‘phosphatase’ in their name, such as Cdc25A phosphatase or tyrosine phosphatase. On the other hand, input of ‘Cdc25_ phosphatase’ finds entries with names like Cdc25A phosphatase, Cdc25B phosphatase and Cdc25C phosphatase. Likewise, input of Cdc% phosphatase finds the same entries as above. In this case, ‘%’ represents ‘25A’, ‘25B’, ‘25C’, respectively. The result of a typical search is illustrated in Figure 2. In this interface, all the therapeutic targets that satisfy the search criteria are listed along with the disease conditions to be treated, drugs or ligands directed at the target, and the drug class. More detailed information of a target can be obtained by clicking the corresponding target name. The result is displayed in an interface shown in Figure 3. From this interface, one finds target name, corresponding disease condition and cross-link to Karolinska disease database (http://www.kib.ki.se/), target function in pathway and corresponding natural ligand, known drugs or ligands directed at the target, drug function (such as inhibitor, antagonist and blocker, etc.), drug therapeutic classification, and additional cross-links to other databases that provide useful information about the target. The functional properties of an identified target can be obtained through cross-linking to the On-line Medical Dictionary (OMD) database (http://www.graylab.ac.uk/omd/) and the SWISS-PROT database (22). The target sequence can be retrieved from cross-link to the SWISS-PROT database. The available 3D structure of this target can be accessed through cross-linking to the Protein Data Bank (PDB) database (23). For an enzymatic target, its nomenclature can be obtained from cross-link to the Enzyme Data Bank (24). Ligand-binding properties may be obtained from cross-link to the Computed Ligand Binding Energy database (CliBE) (http://xin.cz3.nus.edu.sg/group/CLiBE.asp). The related literature can be accessed from cross-link to the relevant entries in the PubMed database (25). As the research in proteomics (26) and pathways (27) progresses, the relevant information can be incorporated or the corresponding databases can be cross-linked to TTD to provide more comprehensive information about the drug targets and their relationship to other biomolecules and cellular processes. * To whom correspondence should be addressed. Tel: +65 874 6877; Fax: +65 774 6756; Email: yzchen@cz3.nus.edu.sg View largeDownload slide Figure 1. The web interface of TTD. Five types of search mode are supported. This database is searchable by target name, disease name, drug/ligand name, drug/ligand function, drug classification or any combination of these. View largeDownload slide Figure 1. The web interface of TTD. Five types of search mode are supported. This database is searchable by target name, disease name, drug/ligand name, drug/ligand function, drug classification or any combination of these. View largeDownload slide Figure 2. The interface of a search result on TTD. All the targets that satisfy the specified search criteria are listed along with disease, drug/ligand name and drug classification. View largeDownload slide Figure 2. The interface of a search result on TTD. All the targets that satisfy the specified search criteria are listed along with disease, drug/ligand name and drug classification. View largeDownload slide Figure 3. Interface of the detailed information of target in TTD. Information related to disease, drug/ligand, pathway and some of the cross-database shortcuts are provided. In the case of one target having multi ligands, the ligands are separated with ‘│’, as well as their functions and CAS numbers. View largeDownload slide Figure 3. Interface of the detailed information of target in TTD. Information related to disease, drug/ligand, pathway and some of the cross-database shortcuts are provided. In the case of one target having multi ligands, the ligands are separated with ‘│’, as well as their functions and CAS numbers. Table 1. Disease names listed in TTD (synonyms of disease names are also included to facilitate searching) Acute lymphoblastic leukemia  Erectile dysfunction  Neuropathic  Addiction  Fever  Obesity  Advanced pancreatic tumor  Fungal infection  Obstructive pulmonary disease  Affective disorder  Gastric tumor  Ocular hypertension/glaucoma  AIDS  Glaucoma  Oral  Allergic rhinitis  Gout  Osteoporosis  Allergy  Heart disease  Ovarian  Alzheimer’s  Heart failure  Pain  Analgesic  Helminth infection  Parkinson’s  Anesthesia  Hepatitis C  Peptic ulcer  ANF degradation  Herpes  Phaeochromocytoma  Angiogenesis  High blood glucose level  Platelet adhesion  Anxiety  High blood sugar level  Platelet disease  Arthritis  High cholesterol  Posterior pituitary disorder  Asthma  Hirsutism  Postsurgical  Autoimmune disease  Hormone-dependent tumors  Prostate adenocarcinoma  B cell  Human African trypanosomiasis  Prostate tumor  Bacterial infection  Hypertension  Prostatic hyperplasia  Baldness  Hyperthyroidism  Psychiatric illness  Blood coagulation  Hypocalcaemia  Psychomotor  Bone Loss  Immune response  Reproduction  Brain ischaemia  Immunodeficiency  Respiration  Breast  In transplantation, etc.  Rheumatoid  Calcium deficiency  Inflammation  Riboflavin deficiency  Cancer  Influenza A and B  Schizophrenia  Carcinoid syndrome  Insomnia  Seizure  Cardiac failure  Irritable bowel syndrome  Smoking  Cardiovascular disease  Kidney failure  Smooth muscle  Chronic myelogenous leukemia  Leukemia  Solid tumor  Cognitive dysfunction  Liposarcoma  Thiamine deficiency  Colon  Liver  Tuberculosis  Common cold  Local anesthetic  Urinary tract infection  Common roundworm  Lung  Urticaria  Congestive heart failure  Lupus  Uterus contraction  Cystic fibrosis  Malaria  Vascular disease  Dementia  Malignant pain  Viral infection  Depression  Melanoma  Visceral  Diabetes  Metastasis  Vitamin A deficiency  Diabetic retinopathy  Migraine  Vitamin B12 deficiency  Diarrhea  Morning sickness  Vitamin B6 deficiency  Drug dependence  Motion sickness  Vitamin C deficiency  Drug induced  Motor disorder  Vitamin D deficiency  Dry eye  Movement disorder  Vomiting  Dysrhythmic  Nasal congestion  Zollinger-Ellison syndrome  Emphysema  Neurodegeneration    Epilepsy  Neurological symptom    Acute lymphoblastic leukemia  Erectile dysfunction  Neuropathic  Addiction  Fever  Obesity  Advanced pancreatic tumor  Fungal infection  Obstructive pulmonary disease  Affective disorder  Gastric tumor  Ocular hypertension/glaucoma  AIDS  Glaucoma  Oral  Allergic rhinitis  Gout  Osteoporosis  Allergy  Heart disease  Ovarian  Alzheimer’s  Heart failure  Pain  Analgesic  Helminth infection  Parkinson’s  Anesthesia  Hepatitis C  Peptic ulcer  ANF degradation  Herpes  Phaeochromocytoma  Angiogenesis  High blood glucose level  Platelet adhesion  Anxiety  High blood sugar level  Platelet disease  Arthritis  High cholesterol  Posterior pituitary disorder  Asthma  Hirsutism  Postsurgical  Autoimmune disease  Hormone-dependent tumors  Prostate adenocarcinoma  B cell  Human African trypanosomiasis  Prostate tumor  Bacterial infection  Hypertension  Prostatic hyperplasia  Baldness  Hyperthyroidism  Psychiatric illness  Blood coagulation  Hypocalcaemia  Psychomotor  Bone Loss  Immune response  Reproduction  Brain ischaemia  Immunodeficiency  Respiration  Breast  In transplantation, etc.  Rheumatoid  Calcium deficiency  Inflammation  Riboflavin deficiency  Cancer  Influenza A and B  Schizophrenia  Carcinoid syndrome  Insomnia  Seizure  Cardiac failure  Irritable bowel syndrome  Smoking  Cardiovascular disease  Kidney failure  Smooth muscle  Chronic myelogenous leukemia  Leukemia  Solid tumor  Cognitive dysfunction  Liposarcoma  Thiamine deficiency  Colon  Liver  Tuberculosis  Common cold  Local anesthetic  Urinary tract infection  Common roundworm  Lung  Urticaria  Congestive heart failure  Lupus  Uterus contraction  Cystic fibrosis  Malaria  Vascular disease  Dementia  Malignant pain  Viral infection  Depression  Melanoma  Visceral  Diabetes  Metastasis  Vitamin A deficiency  Diabetic retinopathy  Migraine  Vitamin B12 deficiency  Diarrhea  Morning sickness  Vitamin B6 deficiency  Drug dependence  Motion sickness  Vitamin C deficiency  Drug induced  Motor disorder  Vitamin D deficiency  Dry eye  Movement disorder  Vomiting  Dysrhythmic  Nasal congestion  Zollinger-Ellison syndrome  Emphysema  Neurodegeneration    Epilepsy  Neurological symptom    View Large Table 2. Drug functions listed in TTD (synonyms of drug functions are also included to facilitate searching) Activator  Cofactor  Agonist  Immunotoxin  Alkylator  Inactivator  Antagonist  Inhibitor  Antibody  Intercalator  Antisense  Opener  Blocker  Stimulator  Chain breaker  Substrate  Coenzyme  Vaccine  Activator  Cofactor  Agonist  Immunotoxin  Alkylator  Inactivator  Antagonist  Inhibitor  Antibody  Intercalator  Antisense  Opener  Blocker  Stimulator  Chain breaker  Substrate  Coenzyme  Vaccine  View Large Table 3. Drug classifications listed in TTD (synonyms of drug classifications are also included to facilitate searching) Anesthetic  Antimalarial  Lipid-lowering  Anti-allergic  Antimotility  Local anesthetic  Anti-allergy  Anti-neurodegenerative  Lupus  Anti-androgen  Anti-obesity  Nasal decongestion  Anti-angiogenic  Antiplatelet  Neurological  Anti-asthmatic  Antipsychotic  Opioid overdose  Antibacterial  Antipyretic  Osteoporosis  Anticancer  Antirheumatoid  Ovulation induction  Anti-cholesterol  Antiseptics  Pain-killer  Anticoagulant  Antiviral  Parkinson’s  Anticonvulsant  Anxiolytic  Platelet  Antidepressant  Anxiotic  Procoagulant  Antidiabetic  Arthritis  Psychomotor stimulant  Antidiarrheal  Bronchodilator  Psychostimulant  Antidiuretic  Cardiotonic  Psychotomimetic  Antidysrhythmic  Contraceptive  Respiratory stimulant  Anti-emetic  Convulsant  Sedative  Anti-emetics  Depressant  Supplement  Antiepileptic  Diuretics  Uterine contractant  Antifungal  Drug dependence  Uterine relaxant  Anti-gastric secretion  Erectile dysfunction  Vasodilator  Antihelminthic  Glaucoma treatment  Vitamin  Anesthetic  Antimalarial  Lipid-lowering  Anti-allergic  Antimotility  Local anesthetic  Anti-allergy  Anti-neurodegenerative  Lupus  Anti-androgen  Anti-obesity  Nasal decongestion  Anti-angiogenic  Antiplatelet  Neurological  Anti-asthmatic  Antipsychotic  Opioid overdose  Antibacterial  Antipyretic  Osteoporosis  Anticancer  Antirheumatoid  Ovulation induction  Anti-cholesterol  Antiseptics  Pain-killer  Anticoagulant  Antiviral  Parkinson’s  Anticonvulsant  Anxiolytic  Platelet  Antidepressant  Anxiotic  Procoagulant  Antidiabetic  Arthritis  Psychomotor stimulant  Antidiarrheal  Bronchodilator  Psychostimulant  Antidiuretic  Cardiotonic  Psychotomimetic  Antidysrhythmic  Contraceptive  Respiratory stimulant  Anti-emetic  Convulsant  Sedative  Anti-emetics  Depressant  Supplement  Antiepileptic  Diuretics  Uterine contractant  Antifungal  Drug dependence  Uterine relaxant  Anti-gastric secretion  Erectile dysfunction  Vasodilator  Antihelminthic  Glaucoma treatment  Vitamin  View Large References 1 Drews,J. 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TI - TTD: Therapeutic Target Database
JF - Nucleic Acids Research
DO - 10.1093/nar/30.1.412
DA - 2002-01-01
UR - https://www.deepdyve.com/lp/oxford-university-press/ttd-therapeutic-target-database-DhDK7ygXOQ
SP - 412
EP - 415
VL - 30
IS - 1
DP - DeepDyve
ER -