MolCode ToolBox
Distributed by CompuDrug
Customer Benefits
The modules of Molcode Toolbox software predict a wide range of experimentally unknown values of properties of compounds including physicochemical, biological, ADME-Tox, ecological pathways/ecotoxicity and adverse drug effects. The modules of Molcode ToolBox software consist of internally encoded computational models built on various datasets related to the aforementioned properties. All the models in Molcode Toolbox are specified by model`s name, CAS-number (not obligatory) and systematic name of compounds, (bio)assay, property/activity value and unit, and reference.
Brief DescriptionMolcode Toolbox is based on proprietary computational models developed by Molcode. With the Molcode Toolbox, the user can load his own compounds, modify the encoded compounds or create/optimize completely new ones, and predict/analyze specific properties of those compounds, as well as create statistical reports for later analysis. The intuitive and clear user interface allows the user to predict the desired properties of compounds in four easy steps/clicks (see "Four easy steps to start"). The expert system is built for Microsoft Windows OS and runs on Windows 2000 or later. The software is very user friendly, making all the complicated steps of QSAR modeling and development invisible to the user. Molcode also provides expert consulting help and services in the following areas:
Why choose Molcode Toolbox?
ADME module
The blood-brain barrier (BBB) is a complex membranous system of brain tissue. In drug discovery and development, the determination of BBB permeation is crucial to design new potential candidates for central nervous system and to avoid undesirable side effects of compounds acting in peripheral tissue. The blood-brain distribution is expressed as the ratio of the steady state molar concentration of a compound in the brain and in the blood: BB=Cbrain/Cblood Permeation constants of test substances were translanted to logarithmic scale (logBB) to reduce the range of the data.
The blood-brain barrier (BBB) is a complex membranous system of brain tissue. In drug discovery and development, the determination of BBB permeation is crucial to design new potential candidates for central nervous system and to avoid undesirable side effects of compounds acting in peripheral tissue. The blood-brain distribution is expressed as the ratio of the steady state molar concentration of a compound in the brain and in the blood: BB=Cbrain/Cblood Permeation constants of test substances were translanted to logarithmic scale (logBB) to reduce the range of the data.
Inhibition of Human Ether-a-go-go Related Gene (hERG) potassium ion channel. The hERG gene (KCNH2) encodes a potassium ion channel responsible for the repolarizing IKr current in the cardiac action potential. Abnormalities in this channel may lead to either Long QT or Short QT syndrome, both potentially fatal cardiac arrhythmia, due to repolarisation disturbances of the cardiac action potential. Among the drugs that can cause QT prolongation, the more common ones include antiarrhythmics, anti-psychotic agents, and certain antibiotics (including quinolones and macrolides). The inhibition values (IC50) of tested substances were converted into logarithmic form to reduce the range of the data.
Drugs bind reversibly with varying degrees of association to human plasma proteins: serum albumin (HSA), alpha-1-acid glycoprotein (AGP), and lipoproteins. Affinity constant k(HSA) ranges from 103 to 1010 M-1. Since the drug-protein complex in the plasma acts as a reservoir for the drug, the degree of binding is an important parameter in pharmacokinetic profiling. Affinity constants were translated to logarithmic scale (logkHSA) to reduce the range of the data.
Drugs bind reversibly with varying degrees of association to human plasma proteins: serum albumin (HSA), alpha-1-acid glycoprotein (AGP), and lipoproteins. Affinity constant k(HSA) ranges from 103 to 1010 M-1. Since the drug-protein complex in the plasma acts as a reservoir for the drug, the degree of binding is an important parameter in pharmacokinetic profiling. Affinity constants were translated to logarithmic scale (logkHSA) to reduce the range of the data.
Caco-2 cells are derived from human epithelial colon adenocarcinoma and retain many morphological and functional properties of the intestinal enterocytes. Caco-2 cell monolayer assay provides information about the drug absorption potential at near physiological conditions. Permeability is represented by the apparent permeability coefficient (Papp) measured in nm/s. The apparent permeability coefficients were translated to logarithmic scale (logPapp) to reduce the range of the data.
PAMPA is an easily automated in vitro drug absorption assay is based on the use of a filter-immobilized artificial lipid (phosphatidylcholine) membrane. Several experimental conditions (different membrane lipid compositions or multiple pH measurements) have been proposed for the determination of artificial membrane permeability values. Permeability is represented by the apparent permeability coefficient (Papp) measured in nm/s. The apparent permeability coefficients were translated to logarithmic scale (logPapp) to reduce the range of the data.
PAMPA is an easily automated in vitro drug absorption assay is based on the use of a filter-immobilized artificial lipid (phosphatidylcholine) membrane. Several experimental conditions (different membrane lipid compositions or multiple pH measurements) have been proposed for the determination of artificial membrane permeability values. Permeability is represented by the apparent permeability coefficient (Papp) measured in nm/s. The apparent permeability coefficients were translated to logarithmic scale (logPapp) to reduce the range of the data.
Physiologically-based pharmacokinetic module
Blood - air partition coefficient, ratio of concentrations achieved between blood and air at equilibrium, is an important physicochemical property for understanding the pulmonary uptake and distribution of volatile chemicals in blood. Blood - air partition coefficient constitutes an integral component in the development of physiologically based pharmacokinetic (PBPK) models. PBPK models allow to correlate and predict toxicokinetics of chemicals in human tissues and thereby contribute to drug discoveries and anesthesiological and toxicological studies. The values of partition coefficient of tested substances were translated to logarithimic scale to reduce the range of the data.
Brain – air partition coefficient, ratio of concentrations achieved between brain and air at equilibrium, is an important physicochemical property for understanding the pulmonary uptake and distribution of volatile chemicals in brain. Brain - air partition coefficient constitutes an integral component in the development of physiologically based pharmacokinetic (PBPK) models. PBPK models allow to correlate and predict toxicokinetics of chemicals in human tissues and thereby contribute to drug discoveries and anesthesiological and toxicological studies. The values of partition coefficient of tested substances were translated to logarithimic scale to reduce the range of the data.
Fat – air partition coefficient, ratio of concentrations achieved between fat and air at equilibrium, is an important physicochemical property for understanding the pulmonary uptake and distribution of volatile chemicals in fat. Fat - air partition coefficient constitutes an integral component in the development of physiologically based pharmacokinetic (PBPK) models. PBPK models allow to correlate and predict toxicokinetics of chemicals in human tissues and thereby contribute to drug discoveries and anesthesiological and toxicological studies. The values of partition coefficient of tested substances were translated to logarithimic scale to reduce the range of the data.
Kidney – air partition coefficient, ratio of concentrations achieved between kidney and air at equilibrium, is an important physicochemical property for understanding the pulmonary uptake and distribution of volatile chemicals in kidney. Kidney - air partition coefficient constitutes an integral component in the development of physiologically based pharmacokinetic (PBPK) models. PBPK models allow to correlate and predict toxicokinetics of chemicals in human tissues and thereby contribute to drug discoveries and anesthesiological and toxicological studies. The values of partition coefficient of tested substances were translated to logarithimic scale to reduce the range of the data.
Liver – air partition coefficient, ratio of concentrations achieved between liver and air at equilibrium, is an important physicochemical property for understanding the pulmonary uptake and distribution of volatile chemicals in liver. Liver - air partition coefficient constitutes an integral component in the development of physiologically based pharmacokinetic (PBPK) models. PBPK models allow to correlate and predict toxicokinetics of chemicals in human tissues and thereby contribute to drug discoveries and anesthesiological and toxicological studies. The values of partition coefficient of tested substances were translated to logarithimic scale to reduce the range of the data.
Muscle – air partition coefficient, ratio of concentrations achieved between muscle and air at equilibrium, is an important physicochemical property for understanding the pulmonary uptake and distribution of volatile chemicals in muscle. Muscle - air partition coefficient constitutes an integral component in the development of physiologically based pharmacokinetic (PBPK) models. PBPK models allow to correlate and predict toxicokinetics of chemicals in human tissues and thereby contribute to drug discoveries and anesthesiological and toxicological studies. The values of partition coefficient of tested substances were translated to logarithimic scale to reduce the range of the data.
Rat fat – air partition coefficient, ratio of concentrations achieved between fat and air at equilibrium, is an important physicochemical property for understanding the pulmonary uptake and distribution of volatile chemicals in fat. Fat - air partition coefficient constitutes an integral component in the development of physiologically based pharmacokinetic (PBPK) models. PBPK models allow to correlate and predict toxicokinetics of chemicals in rat tissues and thereby contribute to drug discoveries and anesthesiological and toxicological studies. The values of partition coefficient of tested substances were translated to logarithimic scale to reduce the range of the data.
Rat liver – air partition coefficient, ratio of concentrations achieved between liver and air at equilibrium, is an important physicochemical property for understanding the pulmonary uptake and distribution of volatile chemicals in liver. Liver - air partition coefficient constitutes an integral component in the development of physiologically based pharmacokinetic (PBPK) models. PBPK models allow to correlate and predict toxicokinetics of chemicals in rat tissues and thereby contribute to drug discoveries and anesthesiological and toxicological studies. The values of partition coefficient of tested substances were translated to logarithimic scale to reduce the range of the data.
Rat Muscle – air partition coefficient, ratio of concentrations achieved between muscle and air at equilibrium, is an important physicochemical property for understanding the pulmonary uptake and distribution of volatile chemicals in muscle. Muscle - air partition coefficient constitutes an integral component in the development of physiologically based pharmacokinetic (PBPK) models. PBPK models allow to correlate and predict toxicokinetics of chemicals in rat tissues and thereby contribute to drug discoveries and anesthesiological and toxicological studies. The values of partition coefficient of tested substances were translated to logarithimic scale to reduce the range of the data.
Anti-ishemia and neuroprotection module
The adenosine A3 receptors are G-protein-coupled receptors that are involved in neuromodulation. In paritcular, A3 receptors play role in pathophysiological pathways during hypoxic stress and other cellular damage. The activation of receptor results in general hypotension and mast-cells degranulation. Selective antagonists are used in clinical practice as anti-inflammatory, neuroprotective and antiasthmatic agents. The inhibition values (Ki) of substances were translated to the logarithmic scale to reduce the range of the data.
Aspartate-specific cysteinyl proteases or caspases have been identified as being key mediators of apoptosis, necrosis and inflammation of mammalian cells. Failure of apoptosis is responsible for a variety of diseases for example tumour development, brain ischemia, myocardial infraction, Huntington`s disease, and Alzheimer`s disease and autoimmune diseases. The inhibition values (IC50) were translated to the logarithmic scale to reduce the range of the data.
Cardiac and vasocontraction module
Opening of the L-type voltage dependent calcium channels causes influx of extracellular Ca2+. This process is responsible for the regulation of many physiological functions, including smooth and cardiac muscle contraction. Calcium channel antagonists (1,4-dihydropyridine derivatives) are used for treatment of cardiovascular diseases such as hypertension and spastic smooth muscle disorders. The IC50 values of tested substances were translated to the logarithmic scale to reduce the range of the data.
Antidepression module
Selective norepinephrine (SNRI) and serotonin reuptake inhibitors (SSRI) are a class of antidepressant used in the treatment of major depression, attention deficit hyperactivity disorder, obsessive-compulsive disorder, chronic pain disorder, and for the relief of menopausal symptoms. The SSRIs potently and selectively inhibit the presynaptic serotonin transporter, thereby increasing serotonin availability at the synapse. IC50 values of SNRIs and SSRIs were translated to the logarithmic scale to reduce the range of the data.
Selective norepinephrine (SNRI) and serotonin reuptake inhibitors (SSRI) are a class of antidepressant used in the treatment of major depression, attention deficit hyperactivity disorder, obsessive-compulsive disorder, chronic pain disorder, and for the relief of menopausal symptoms. The SSRIs potently and selectively inhibit the presynaptic serotonin transporter, thereby increasing serotonin availability at the synapse. IC50 values of SNRIs and SSRIs were translated to the logarithmic scale to reduce the range of the data.
Anticonvulsant module
Benzodiazepines (BZDs) are anxiolytics and hypnotic-sedative drugs which exert their pharmacological actions via interactions with a discrete neuronal site on the GABAA Receptor-Benzodiazepine Receptor-Chloride Ion Channel Complex. BZD receptor agonists and GABA receptor agonists are positive allosteric effectors to each other, e.g. BZD binding induces the GABA receptor to shift from a low affinity state to a high affinity state. IC50 values of tested substances were translated to the logarithmic scale to reduce the range of the data.
Chemotherapy (anti-tumor, anti-leukemia) module
The ubiquitin–proteasome ATP-dependent pathway is involved in the development of a number of diseases, such as cancer, Alzheimer’s, Parkinson’s, diabetes, etc. It has been demonstrated that chemically different cell-permeable proteasome inhibitors are able to induce apoptosis abundantly in p53-defective leukemic cell lines as well as in myelogenic and lymphatic leukemic cells. The inhibition values (IC50) of substances were translated to the logarithmic scale to reduce the range of the data.
Platelet-derived growth factor (PDGF) and its corresponding receptor tyrosine kinase (PDGFR) have become important targets for inhibition of the proliferation of endothelial cells, the main component of blood vessels. Uncontrolled formation of blood vessel (angiogenesis) is a characteristic of cancer. The compounds such as 4-piperazinylquinazoline, 3-arylquinolines, phenylaminopyramidines and 1-phenylbenzimidazoles have been reported as selective inhibitors of PDGFR. The inhibition values (IC50) of tested substances were converted into logarithmic scale to reduce the range of the data.
The cyclin-dependent kinases (CDKs) are key regulators of the cell cycle. Abnormal expression of CDK-2 has been detected in colorectal, ovarian, breast, and prostate cancers. CDK-2 inhibitors have been shown to induce apoptosis in different tumor cell lines acting as potential anticancer therapeutics. The inhibition values (IC50) of tested substances were translated to logarithmic scale to reduce the range of the data.
The cyclin-dependent kinases (CDKs) are key regulators of the cell cycle. Abnormal expression of CDK-2 has been detected in colorectal, ovarian, breast, and prostate cancers. CDK-2 inhibitors have been shown to induce apoptosis in different tumor cell lines acting as potential anticancer therapeutics. The inhibition values (IC50) of tested substances were translated to logarithmic scale to reduce the range of the data.
Alzheimer disease module
Alzheimer’s disease is a progressive, neurodegenerative disorder, which results in memory loss and behavioral abnormalities, and is characterized by the accumulation of β-amyloid peptides and neurofibrillary tau protein tangles in neural tissues and vessels. The serine/threonine kinase cdk5/p25 complex is responsible for hyperphosphorylation of tau and formation of neurofibrillary tangles. The inhibition values (IC50) of cdk5/p25 complex inhibitors were converted into logarithmic scale to reduce the range of the data.
Inhibition of Glycogen Synthase Kinase-3 (GSK-3α and GSK-3β) These protein kinases catalyze the phosphorylation of various proteins involved in the mechanisms that regulate the metabolism and functioning of cells. Glycogen Synthase Kinase-3 (GSK-3) is a multifunctional serine/threonine kinase ubiquitously expressed in mammalian tissues. It is involved in multiple physiological processes including the cell cycle regulation, response to DNA damage, insulin action on glycogen synthesis, HIV-1 Tat-mediated neurotoxicity, hyperphosphorylation of tau, circadian rhythm, and others. The inhibition values (IC50) of tested substances were converted into logarithmic scale to reduce the range of the data.
Inhibition of Glycogen Synthase Kinase-3 (GSK-3α and GSK-3β) These protein kinases catalyze the phosphorylation of various proteins involved in the mechanisms that regulate the metabolism and functioning of cells. Glycogen Synthase Kinase-3 (GSK-3) is a multifunctional serine/threonine kinase ubiquitously expressed in mammalian tissues. It is involved in multiple physiological processes including the cell cycle regulation, response to DNA damage, insulin action on glycogen synthesis, HIV-1 Tat-mediated neurotoxicity, hyperphosphorylation of tau, circadian rhythm, and others. The inhibition values (IC50) of tested substances were converted into logarithmic scale to reduce the range of the data.
Alzheimer’s disease is a progressive, neurodegenerative disorder, which results in memory loss and behavioral abnormalities, and is characterized by the accumulation of β-amyloid peptides and neurofibrillary tau protein tangles in neural tissues and vessels. β-amyloid peptides are generated by sequential proteolytic cleavage of amyloid precursor protein (APP) by the action of β- and γ-secretases. Several γ-secretase inhibitors have been shown to reduce the formation of the toxic β-amyloid peptides. The inhibition values (IC50) of tested substances were converted into logarithmic scale to reduce the range of the data.
Obesity and diabetis module
Inhibition of Glycogen Synthase Kinase-3 (GSK-3α and GSK-3β) These protein kinases catalyze the phosphorylation of various proteins involved in the mechanisms that regulate the metabolism and functioning of cells. Glycogen Synthase Kinase-3 (GSK-3) is a multifunctional serine/threonine kinase ubiquitously expressed in mammalian tissues. It is involved in multiple physiological processes including the cell cycle regulation, response to DNA damage, insulin action on glycogen synthesis, HIV-1 Tat-mediated neurotoxicity, hyperphosphorylation of tau, circadian rhythm, and others. The inhibition values (IC50) of tested substances were converted into logarithmic scale to reduce the range of the data.
Inhibition of Glycogen Synthase Kinase-3 (GSK-3α and GSK-3β) These protein kinases catalyze the phosphorylation of various proteins involved in the mechanisms that regulate the metabolism and functioning of cells. Glycogen Synthase Kinase-3 (GSK-3) is a multifunctional serine/threonine kinase ubiquitously expressed in mammalian tissues. It is involved in multiple physiological processes including the cell cycle regulation, response to DNA damage, insulin action on glycogen synthesis, HIV-1 Tat-mediated neurotoxicity, hyperphosphorylation of tau, circadian rhythm, and others. The inhibition values (IC50) of tested substances were converted into logarithmic scale to reduce the range of the data.
REACH properties. Toxicity module
The bacterial reversed mutation assay (Ames Test) is used to detect point mutations, which involve substitution, addition or deletion of one or a few DNA base pairs. The test uses bacterial culture of amino acid-dependent strain of Salmonella typhimurium (TA98 or TA100), which is exposed to the test substance in the presence and in the absence of an exogenous metabolic activation system [cofactor-supplemented post-mitochondrial fraction (S9) prepared from the liver]. Mutagenic compounds cause an increase in the number of revertant colonies relative to the background level. The mutagenic potencies of tested substances are expressed as log(revertants/nmol). For nonmutagenic compounds, the potency is arbitrarily coded as -100.
MolCode ToolBox is operating under Windows computing platform.
If you need more information about our product, please e-mail CompuDrug International at abc@compudrug.com
 |
CompuDrug - Your Expert in Chemical Informatics
