Around half of all drugs in clinical development fail to commercialize because of poor ADME and toxicity properties. There is increasing interest in the early prediction of ADME properties, in order to increase the success rate of compounds
reaching development. Using the PreADME the result of ADME prediction can be used as the most outstanding and practical guidance for the early drug discovery.
Molecular descriptor calculation tool predicts various physicochemical properties concerned with drug
discovery, such as logP and water solubility and calculates diverse descriptors calculation tools for
QSAR
(quantitative structure-activity relationship).
Drug-likeness prediction tool is for chemical library design and ADME prediction tool predicts ADME
(Absorption, Distribution, Metabolism and Excretion)properties.
There are two versions of PreADME application: PC-based PreADME and Web-based PreADME. PC-based
PreADME is a commercial product and Web-based PreADME is a trial version for PC-based PreADME.
PC-based PreADME interfaces
PC-based PreADME is easy to use with user-friendly interfaces and
handles large numbers of compounds.
A molecular set for colleting molecules you are interested in A data table window for editing and entering chemical data Over 900 2D molecular descriptors including constitutional, electrostatic, physicochemical,geometrical
and topological descriptors Prediction for solubility in pure water and solubility in buffer system. Fast computation: 200,000 compounds/hour (Pentium 4 1.6GHz, 256 RAM) Screening of drug-like compounds from drug candidates by rule-based predictions Prediction of ADME properties related to absorption and distribution of molecules
- Permeability through Caco-2 cell and MDCK cell
- Blood-brain barrier permeability
- Human intestinal absorption (HIA)
- Skin permeability
- Plasma protein binding Chemical library design by using descriptors and ADME items
Windows 98/Me/2000/XP/2003 server Prerequirement : Ms .net Framework 1.1 Pentium 133MHz higher Hard(15MB), RAM(128MB)
1) Descriptor Calculation: Over 1000 Molecular Descriptors Constitutional descriptors (148)
No. donors, acceptors, rotatable bonds .....
Atom counts, Bond counts, Ring counts......
41 diverse functional indicators.....
structure checking descriptors (No. components, No. inorganic atoms.....
23 Reactive group responsible for in vitro false positive..... Electrostatic descriptors (78)
MPEOE atomic charge
Maximum and minimum partial charge of element
Charged parital surface area descriptors
Geometrical descriptors (16)
VDW volume, surface
Hbond donor, acceptors, (+) and (-) charged group surface area
Topological polar surface area Physicochemical descriptors (10)
logP, logD
logS(pure water solubility), logSb(buffer solubility)
boiling point, melting point, vapor pressure
refractivity, polarizability, solvation free energy AlogP98 atomic types (120) Topological descriptors (688)
Autocorrelation
(Mass, MPEOE charge, Electronegativity, E-state, AlogP98, VDW radius, Polarizability)
Adjacency and distance matrix based descriptors
BCUT descriptors
(Mass, MPEOE charge, Electronegativity, E-state, AlogP98, VDW radius, Polarizability)
Kier & Hall molecular connectivity
Kappa & Kappa alpha descriptors
Information content descriptors
Galvez topological charge indices
Electrotopological state indices (E-state) - Atom types and Hydrogen types
Information contents related descriptors
AI topological indices
Drug-likeness prediction tools of
PreADME
In recent years, compounds to synthesize and estimate potential
for drug through combinatorial chemistry and high throughput
screening have rapidly increased in drug discovery.
As the above cause, need for minimizing extremely time-consuming steps of synthesis and biological screening is of important interest
and need for good tools for predicting drug-likeness has also
increased.
One of tools for predicting drug-likeness, discriminating between
drug-like compounds and non-drug compounds uses widely.
PreADME provides five drug-like rules: Rule of Five (Lipinski’s rule), Lead-like rule, CMC-like rule, MDDR-like rule and WDI-like rule.
Predicting ADME properties at an early stage of drug discovery and development process is very
important to remove compounds with poor pharmacokinetic properties and minimize extremely expense-
and time-consuming steps. Therefore, Computational ADME prediction currently is considered a valuable
tool for successful lead optimization.
PreADME includes absorption (Caco-2 cell & MDCK cell permeability, human intestinal absorption and skin permeability) and distribution (brain-blood barrier penetration and plasma protein binding) prediction tools. To develop these prediction models, genetic functional approximation and back-propagation neural network were used.
Absorption Prediction
Currently, in vitro methods such as Caco-2 or MDCK monolayers permeability or in vivo methods of
HIA (Human Intestinal Absorption) are widely used to estimate oral absorption. Using PreADME, you can predict Caco-2 cell permeability (PCaco-2 ×10-6 cm/sec), MDCK cell permeability (PMDCK×10-6 cm/sec) and HIA (%) with computational method. In addition, Skin permeability
(Kp cm/hr) prediction tool is provided. This is important property in the pharmaceutical, cosmetic and
agrochemical fields.
Distribution Prediction
ADME prediction tools of PreADME
PreADME provides blood-brain barrier (BBB) penetration and plasma protein binding prediction tools. Both properties are related to distribution of drugs.
BBB penetration prediction is crucial in pharmaceutical sphere because CNS-active compounds must pass across it and CNS-inactive compounds mustn’t do it in order to avoid of CNS side effects. Using PreADME, you can predict [Brain]/[Blood], where [Brain] and [Blood] are the steady-state concentration of radiolabeled compounds in brain and peripheral blood and in vivo data on rates.
Plasma protein binding prediction tool predicts percent drug bound in plasma protein as in vitro data on human. This is important because a degree of plasma protein binding of a drug influences not only the drug’s action but also its disposition and efficacy.
The Opening Screen of Web-based PreADME
Web-based PreADME is the trial version for PC-based
PreADMET. First, you have to register in order to evaluate
PreADME at http://preadmet.bmdrc.org/ After register, you
can log in and use PreADME web version.
Web-based PreADME also provides Molecular Descriptor
Calculation, Drug-likeness Prediction, ADME Prediction And
toxicity prediction. You can calculate properties for only one
chemical structure at a time and download the prediction result. Data file formats available on web-based PreADME are *.mol for upload and *.sdf for download.
The next version of PreADME is PreADMET and will include the below:
Over 1400 3D Molecular descriptors Chemical Structure Drawing tool Convert 2D structure into 3D structureToxicity Prediction
- Mutagenicity
- Carcinogenicity Combinatorial Library Builder Diverse Chemical Library Design tool
PreADME
Home>Products&Sercvicet>PreADME
PC-based PreADME interfaces
A molecular set for colleting molecules you are interested in
Constitutional descriptors (148) 
Electrostatic descriptors (78) 
Physicochemical descriptors (10) 
AlogP98 atomic types (120) 
Topological descriptors (688) 
