What is ADMET Predictor™?

ADMET Predictor is sophisticated, yet very easy to use, computer software for advanced predictive modeling of ADMET properties. The "ADMET" acronym is commonly used in the pharmaceutical industry to indicate all the phenomena associated with Absorption, Distribution, Metabolism, Elimination, and Toxicity of chemical substances in the human body. ADMET Predictor not only rapidly estimates a number of vital ADMET properties (listed below) from molecular structures, but is also capable of building predictive models of new properties from user's data via its integrated ADMET Modeler™ module. The program predictions can be further utilized as inputs for our software products GastroPlus™ and MedChem Studio™, or used internally by a flexible screening filter ADMET Risk that can include any combination of predicted properties.

What makes ADMET Predictor unique?

• ACCURACY: its predictive models have been consistently ranked as the most accurate by independent third party comparisons (see the "Publications" link for details).
• SPEED: it can process up to 250,000 compounds per hour on a notebook PC.
• EASE OF USE: using the program is as simple as opening a file containing molecular structures.
• OUTPUT OPTIONS: it provides a variety of output channels to store, transfer, or visualize its results quickly and efficiently.
• BATCH CAPABILITY: it has a built-in batch mode and can run as a Pipeline Pilot™ component.

What does it predict?

Physico-Chemical and Biopharmaceutical Module

• pK_a (ionization constants; a multiprotic model)
• Human effective permeability in jejunum (Peff)
• MDCK apparent permeability (Papp)
• NEW! Corneal permeability
• Solubility
  • - Native solubility (solubility in pure water)
  • - Native pH at saturation in pure water
  • - Intrinsic solubility in pure water
  • - Salt solubility factor
  • - Water solubility at user-specified pH
  • - NEW! Solubility in the simulated gastrointestinal fluids: FaSSGF, FaSSIF, and FeSSIF
• Supersaturation ratio (a tendency to supersaturate in water)
• logP (two models: artificial neural network ensemble and Moriguchi)
• logD (estimation of octanol-water distribution coefficient at user-defined pH)
• Diffusion coefficient in water (Hayduk-Laudie formula)
• Molal volume (Schroeder formula)
• Blood-brain barrier permeation
• Human plasma protein binding as percent unbound
• Human volume of distribution
• Blood-to-plasma concentration ratio
• Activity models
• - Inhibition of HIV integrase mediated strand transfer
• - Inhibition of HIV integrase mediated 3' processing

Toxicity Module

• Estrogen receptor toxicity (two models: qualitative and, if toxic, quantitative ratio of IC₅₀ estradiol/IC₅₀ compound)
• Maximum recommended therapeutic dose (MRTD)
• NEW! Environmental bioconcentration factor (a.k.a. bioaccumulation factor)
• Fathead minnow lethality as LC₅₀
• NEW! Allergenic skin sensitization
• NEW! Acute toxicity in rats as LD₅₀
• Carcinogenicity in rats as TD₅₀
• Carcinogenicity in mice as TD₅₀
• Qualitative filter of mutagenicity in 10 strains of salmonella bacteria
• hERG-encoded K⁺ channel affinity as pIC₅₀
• Acute toxicity in Tetrahymena Pyriformis as pIGC₅₀ (growth inhibition)
• Human liver adverse effects of drugs as the binary likelihood of causing elevation in diagnostic liver enzymes: alkaline phosphatase, SGOT, SGPT, LDH, and GGT.

Enslein Metabolism Module

• Michaelis-Menten kinetic K_m constants for hydroxylation reaction catalyzed by five CYP P450 enzymes: 1A2, 2C9, 2C19, 2D6, 3A4 (five models)
• Michaelis-Menten kinetic V_max constants for hydroxylation reaction catalyzed by five CYP P450 enzymes: 1A2, 2C9, 2C19, 2D6, 3A4 (five models)
• Intrinsic clearance, CL_int, resulting from metabolic activity of five CYP P450 enzymes: 1A2, 2C19, 2C9, 2D6, and 3A4 (five models)
• General inhibitory properties against four CYP P450 enzymes: 1A2, 2C9, 2D6, and 3A4 (four models)
• Specific inhibitory properties against 3A4-mediated metabolism of midazolam and testosterone (two models)
• Specific inhibitory constant K_i against 3A4-mediated metabolism of midazolam and testosterone (two models)
• Classification of whether a molecule will be glucuronidated by one of the seven isoforms of the Uridine 5'-Diphosphate-Glucuronosyltransferase (UGT): 1A1, 1A3, 1A4, 1A6, 1A9, 1A10, and 2B7.

Simulation Module

• Fraction absorbed in human (by simulation at 1 mg, 10 mg, 100 mg, and 1000 mg dose levels)
• Optimal dose in human, in mg, matching desired efficacious concentration in blood plasma

Customizable ADMET Risk filter

• An analog of the Lipinski's Rule of Five, but more flexible and discriminating

If your quantity of interest is not listed above, then you can use the integrated ADMET Modeler module to easily build and append an appropriate predictive model to ADMET Predictor!

What other features does the program offer?

Descriptor Sensitivity Analysis

• Interpretation of model predictions in structural terms for guided design of molecule's derivatives with desired ADMET properties

Associative modeling

• Extending the scope of ADMET predictions using your own data, without the need to retrain the underlying models (a.k.a. "LIBRARY Mode")

Detailed Structure Depiction

• Graphical map of atomic charge, polarizability, E-state, and reactivity distributions

2D Graphing

• Distribution histograms, and correlation graphs

4D Data Mining

• Data display in a rotatable 3D scatter plot. Individual points may be colored by a fourth variable.
• An integrated Miner3D graphics component.

What input formats does it support?

• SMILES strings (2D predictive models only)
• ISIS/Base™ Structure Data Format (SDF)
• ISIS/Base Reaction Data Format (RDF)
• ISIS/Draw™ Molecular Structure Format (MOL)
• ChemDraw™ Structure Molfile (MOL)
• Tripos/SYBYL™ Structure Format (MAC)

Compatibility

• ADMET Predictor comes now with fully integrated ADMET Modeler module - a software application for building powerful predictive models based on Artificial Neural Networks, Support Vector Machines, Multiple Linear Regression, and Kernel Partial Least Squares.
• ADMET Predictor outputs are 100% compatible with GastroPlus - a software application developed by Simulations Plus for simulating the oral absorption, distribution, metabolism and excretion of drugs.
• MedChem Studio - our intuitive cheminformatics platform can run ADMET Predictor as its module providing on-the-fly property predictions.
• Input and output of ADMET Predictor are fully compatible with SDF, RDF and MOL file formats used by ISIS/Base and ISIS/Draw.
• ADMET Predictor can be run in batch mode from command line, which makes it suitable for incorporation into automated data flow control software, such as Pipeline Pilot. (A suitable Pipeline Pilot component is distributed with the program.)
• ADMET Predictor easily interfaces with ACD/PhysChem Batch™ software for the purpose of predicting the ionization constants (pK_a).

ISIS/Base and ISIS/Draw are trademarks of MDL(R) Information Systems, Inc. Pipeline Pilot is a trademark of SciTegic, a wholly owned subsidiary of Accelrys, Inc. ACD/PhysChem Batch is a trademark of Advanced Chemistry Development, Inc.