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About ADMET
ADMET
ADME is an abbreviation in pharmacokinetics and pharmacology for "absorption, distribution, metabolism, and excretion," and describes the disposition of a pharmaceutical compound within an organism. The four criteria all influence the drug levels and kinetics of drug exposure to the tissues and hence influence the performance and pharmacological activity of the compound as a drug. ADME sometimes takes the potential or real toxicity of compound into account together, namely ADME-Tox or ADMET. [Wikipedia]
Absorption
For a compound to reach a tissue, it usually must be taken into the bloodstream - often via mucous surfaces like the digestive tract (intestinal absorption) - before being taken up by the target cells. Factors such as poor compound solubility, gastric emptying time, intestinal transit time, chemical instability in the stomach, and inability to permeate the intestinal wall can all reduce the extent to which a drug is absorbed after oral administration. Absorption critically determines the compound's bioavailability. Drugs that absorb poorly when taken orally must be administered in some less desirable way, like intravenously or by inhalation. Routes of administration is an important consideration. [Wikipedia]
Distribution
The compound needs to be carried to its effector site, most often via the bloodstream. From there, the compound may distribute into muscle and organs, usually to differing extents. After entry into the systemic circulation, either by intravascular injection or by absorption from any of the various extracellular sites, the drug is subjected to numerous distribution processes that tend to lower its plasma concentration. Distribution is defined as the reversible transfer of a drug between one compartment to another. Some factors affecting drug distribution include regional blood flow rates, molecular size, polarity and binding to serum proteins, forming a complex. Distribution can be a serious problem at some natural barriers like the blood–brain barrier. [Wikipedia]
Metabolism
Compounds begin to break down as soon as they enter the body. The majority of small-molecule drug metabolism is carried out in the liver by redox enzymes, termed cytochrome P450 enzymes. As metabolism occurs, the initial (parent) compound is converted to new compounds called metabolites. When metabolites are pharmacologically inert, metabolism deactivates the administered dose of parent drug and this usually reduces the effects on the body. Metabolites may also be pharmacologically active, sometimes more so than the parent drug. [Wikipedia]
Excretion
Compounds and their metabolites need to be removed from the body via excretion, usually through the kidneys (urine) or in the feces. Unless excretion is complete, accumulation of foreign substances can adversely affect normal metabolism. There are three main sites where drug excretion occurs. The kidney is the most important site and it is where products are excreted through urine. Biliary excretion or fecal excretion is the process that initiates in the liver and passes through to the gut until the products are finally excreted along with waste products or feces. The last main method of excretion is through the lungs. [Wikipedia]
Toxicity
When the compound has poor ADME properties, it may induce unsatisfied efficacy or even toxicity in body. The molecular mechanisms underlying drug toxicity in clinic are mostly unrevealed; however, the unexpected drug-protein interactions (both on-target and off-target) are one of the key factors. Drug-induced toxicity related proteins (DITRPs) are proteins that mediate toxicities through their binding to drugs or reactive metabolites. Collection of these proteins facilitates better understanding of the molecular mechanisms of drug-induced toxicity.
About Pathway
ADMET Pathway
ADMET pathways illustrate the whole life span of drug, from absorption into body to excretion out of body, in a way of drug/metabolite-protein interaction network. Normally, six pathways are available for each drug: an ADMET combo pathway that gives the framework of pharmacokinetics and five detailed pathways particular for each of the ADMET processes. Unlike other pharmacokinetics pathways, the ADMETNet pathways emphasize on how drug behaves in body with the help of proteins. This includes a buddle of proteins that aid drug absorption into gastrointestinal tract and vessel, drug penetration across cell membrane and distribution into different tissues, drug metabolism into active metabolites or other byproducts in liver, drug excretion out of body via all routes, and drug-induced toxicity. Key pharmacokinetics parameters are also presented in the pathways when available.
Pathway Interpretation
Pathway Legends:
Reaction, Transportation
Small Molecule Drug
Metabolites
Induction
Inhibition
Feces
Urine
Body Fluid
Cell Membrane
Transporters
Carriers
CYP Emzymes
Other Enzymes
Targets
Toxicity Related Protein
Drug-Carrier Compound
Toxicity
Transporters:
E_BBM_E
Represent transporters on the Brush Border Membrane of Enterocyte for Exporting drug from the cell.
E_BBM_I
Represent transporters on the Brush Border Membrane of Enterocyte for Importing drug to the cell.
E_BLM_E
Represent transporters on the BasoLateral Membrane of Enterocyte for Exporting drug from the cell.
E_BLM_I
Represent transporters on the BasoLateral Membrane of Enterocyte for Importing drug to the cell.
K_BBM_E
Represent transporters on the Brush Border Membrane of Renal tubular epithelial cell (Kidney) for Exporting drug from the cell.
K_BBM_I
Represent transporters on the Brush Border Membrane of Renal tubular epithelial cell (Kidney) for Importing drug to the cell.
K_BLM_E
Represent transporters on the BasoLateral Membrane of Renal tubular epithelial cell (Kidney) for Exporting drug from the cell.
K_BLM_I
Represent transporters on the BasoLateral Membrane of Renal tubular epithelial cell (Kidney) for Importing drug to the cell.
K_Others
Represent transporters which expressed in Kidneys while their subcellular localizations are unknown.
H_SM_E
Represent transporters on the Sinusoidal Membrane of Hepatocyte for Exporting drug from the cell.
H_SM_I
Represent transporters on the Sinusoidal Membrane of Hepatocyte for Importing drug to the cell.
H_CM_E
Represent transporters on the Canalicular Membrane of Hepatocyte for Exporting drug from the cell.
H_CM_I
Represent transporters on the Canalicular Membrane of Hepatocyte for Importing drug to the cell.
H_Others
Represent transporters which expressed in Hepatocyte while their subcellular localizations are unknown.
P_LM_E
Represent transporters on the Lateral Membrane of Placenta for Exporting drug from the cell.
P_LM_I
Represent transporters on the Lateral Membrane of Placenta for Importing drug from the cell.
P_Others
Represent transporters which expressed in Placenta while their subcellular localizations are unknown.
B_LM_E
Represent transporters on the Lateral Membrane of Brain for Exporting drug from the cell.
B_LM_I
Represent transporters on the Lateral Membrane of Brain for Importing drug from the cell.
B_Others
Represent transporters which expressed in Brain while their subcellular localizations are unknown.
Inhi_trans
Represent transporters which expressed in other tissues/cells and act as Inhibitors.
Indu_trans
Represent transporters which expressed in other tissues/cells and act as Inducers.
Sub_trans
Represent transporters on the Substrate which expressed in other tissues/cells.
Others
Represent transporters which expressed in other tissues/cells while their relationships with drug are unknown.
Guideline
About Browse
The Browse allows rapid data retrieval in four modes: by drug, by drug category, by protein, and by ADMET class.

Step 1: Select a mode (eg. 'By Protein') from the left dropdown menu.

Step 2: Select a specific mode (eg. 'Transporter') from the right dropdown menu to tailored options.

Step 3: The corresponding result will be listed, and clicking on the certain Uniprot AC will lead you to the information page.

Please note: other characters are not allowed except following characters:
                          'A-Z', 'a-z', '0-9', '_', '-', ' '.
About Quick Search
The Quick Search allows searching drug or protein with keyword of drug name, drug ID of BADD, DrugBank ID, Molecular Formula, ADT number, CAS number, KEGG ID, PubChem ID, protein name, gene symbol, Uniprot AC, Entrez gene ID and Ensembl gene ID.

Step 1: Select 'Drug' or 'Protein' from the dropdown menu.

Step 2: Enter the keyword you want to search, eg. 'Abacavir'. You can choose 'Fuzzy Search' or 'Accurate Search' to extend the number of result or get the accurate result.

Step 3: Click the Submit button to initiate searching.

Step 4: The corresponding result will be listed, and clicking on the certain drug name or structure will lead you to the information page.

Please note: other characters are not allowed except following characters:
                          'A-Z', 'a-z', '0-9', '_', '-', ' '.
About Advance Search
The Advance Search allows searching drug or protein with the combination of different kinds of keywords.

Step 1: Select 'Drug' or 'Protein' from the first dropdown menu.

Step 2: Select protein type (eg. 'Enzyme'), ADMET class (eg. 'M') or drug category from the latter dropdown menus or check boxes, and/or enter protein name, gene symbol (eg. 'CYP') or drug name in the corresponding textbox.

Step 3: Click the Submit button to initiate searching.

Step 4: The corresponding result will be listed, and clicking on the certain Uniprot AC will lead you to the information page.

Please note: other characters are not allowed except following characters:
                          'A-Z', 'a-z', '0-9', '_', '-', ' '.
About SMILES Search
The SMILES Search allows searching drug with a SMILES string.

Step 1: Enter the SMILES string in the textbox.

Step 2: Select the 'Accurate' or 'Fuzzy' to obtain the drug with tha same structure or drugs which containing the searching structure.

Step 3: Click the Submit button to initiate searching.

Step 4: The corresponding result will be listed and sorted by structure similarity.

About Structure Search
The Structure Search allows drawing or uploading a chemical structure in the JSDraw panel, converting the structure into canonical SMILES string automatically, and searching drug with the SMILES string.

Step 1: Draw or upload the drug structure in the JSDraw panel.

Step 2: Select the 'Accurate' or 'Fuzzy' to obtain the drug with tha same structure or drugs which containing the searching structure.

Step 3: Click the Submit button to initiate searching.

Step 4: The corresponding result will be listed and sorted by structure similarity.

Note: This tool is powered by power JSDraw.
About ID Mapping
The ID Mapping allows mapping one of the following identifiers or items between each other:
Drug Name, BADD DID, ATC, CAS RN, TTD ID, ChEBI ID, PubChem CID, ChemSpider ID, DrugBank ID, KEGG ID, Protein Name, Uniprot AC, Uniprot ID, Gene Symbol, Entrez Gene ID, Ensemble Gene ID, PDB ID, EMBL ID, STRING ID, Reactome ID, PharmGKB Drug, PharmGKB Pathway, SMPDB Action Pathway, and SMPDB Metabolism Pathway.

Step 1: Enter identifiers, separated by semicolons, in the form field.

Step 2: Select source type and target type from the dropdown menus.

Step 3: Click the Go button to initiate searching.

Statistics
Drug Statistics
Number of approved small molecular drugs
1,541
Number of drugs with transporter data
722
Number of drugs with carrier data
170
Number of drugs with enzyme data
1,016
Number of drugs with target data
1,389
Number of drugs with toxicity related protein data
248
Protein Statistics
Number of proteins
1,974
Number of transporters
175
Number of carriers
19
Number of enzymes
304
Number of targets
1,492
Number of toxicity related proteins
352
Number of drug-protein pairs
13,459
ADMET Statistics
Number of proteins involved in drug absorption
132
Number of proteins involved in drug distribution
187
Number of proteins involved in drug metabolism
304
Number of proteins involved in drug excretion
132
Number of proteins involved in drug toxicity
352
Number of proteins involved in drug efficacy
1,492
Pathway Statistics
Number of pathways
7,159
Number of ADMET combo pathways
1,541
Number of absorption pathways
1,541
Number of distribution pathways
1,541
Number of metabolism pathways
747
Number of excretion pathways
1,541
Number of toxicity pathways
248
ADMET Parameter Statistics
Number of ADMET parameters
35
Number of drug-ADMET parameters
21,769
Citing
Citing ADMETNet
Xu Q, Liu K, Lin XM, Qin YM, Chen LS, Cheng J, Zhong MD, He QS, Li YB, Wang TW, Pan JB, Peng ML, Yao LX, Ji ZL. (2017) ADMETNet: the knowledgebase of pharmacokinetics and toxicology network. Journal of Genetics and Genomics. doi: 10.1016/j.jgg.2017.04.005.
Related References
ADReCS
Cai MC, Xu Q, Pan YJ, Pan W, Ji N, Li YB, Jin HJ, Liu K, Ji ZL. (2015) ADReCS: an ontology database for aiding standardization and hierarchical classification of adverse drug reaction terms. Nucleic Acids Res. 43(Database issue): D907-D913.
DITOP
Zhang JX, Huang WJ, Zeng JH, Huang WH, Wang Y, Zhao R, Han BC, Liu QF, Chen YZ, Ji ZL. (2007) DITOP: drug-induced toxicity related protein database. Bioinformatics. 23: 1710–1712.
PaGenBase
Pan JB, Hu SC, Shi D, Cai MC, Li YB, Zou Q, Ji ZL. (2013) PaGenBase: a pattern gene database for the global and dynamic understanding of gene function. PLoS ONE. 8(12): e80747.
Credits & Contact
Please feel free to contact Professor Zhiliang Ji with respect to any details pertaining to ADMETNet.
Address
School of Life Sciences, Xiamen Univesity, Xiamen 361102, Fujian, P.R.China
Phone
+86-592-2182897
Fax
+86-592-2182897
Email
appo@xmu.edu.cn (Prof. ZL Ji)
Lab Webpage
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