ADMET Predictor® User Manual
ADMET Predictor® User Manual
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2.4. PhysChem and Biopharm Properties

2.4. PhysChem and Biopharm Properties

Models in the PhysChem attribute group are enabled by the Physicochemical and Biopharmaceutical license. Its contributions to the overall ADMET Risk are captured in the Absorption Risk model ([Absn_Risk]).

The group includes models for:

  • ionization (pKa)

  • S+Acidic_pKa, S+Mixed_pKa, S+Basic_pKa, S+pK50 and microstate analysis for visualizing microscopic ionization relationships and generating ionization profiles as a function of pH.

  • partition coefficients

  • gas:water partition coefficient (Henry's Law constant; logHLC).

  • octanol-water partition coefficient: our implementation of Moriguchi's model (MlogP) and our own model (S+logP)

  • octanol-water partition coefficient as a function of pH (S+logD).

  • solubility

  • aqueous solubility of in pure water (S+Sw) and at a specified pH (S+S_pH).

  • pH at saturation (S+pH_satd), intrinsic solubility (S+S_Intrins) and solubility factor for salts (SolFactor).

  • solubility in simulated fasted gastric fluid (S+FaSSGF), in simulated fasted intestinal fluid (S+FaSSIF) and simulated fed intestinal fluid (S+FeSSIF).

  • melting point in degrees Celsius (S+MP)

  • tendency to form supersaturated solutions (SupSatn).

  • free energy of self solvation (DG_SelfSolv) and free energy of hydration (DG_Hydration) (optional).

  • permeability

  • effective jejunal permeability (S+Peff and optional SimplePeff)

  • permeability through Madin-Darby canine kidney cell layers (S+MDCK and S+MDCK-LE).

  • permeability through PAMPA membranes (S+PAMPA)

  • diffusion coefficient (DiffCoef) as well as skin and corneal permeability (Perm_Skin and Perm_Cornea)

  • blood-brain barrier penetration and retention (BBB_Filter and logBB)

  • pharmacokinetic parameters:

  • fraction unbound to protein in human plasma (fup_hum)

  • fraction unbound to protein in rat plasma (fup_rat)

  • fraction unbound to protein in mouse plasma (fup_mou)

  • fraction unbound to protein in dog plasma (fup_dog)

  • fraction unbound to protein in monkey plasma (fup_mky; combines cynomolgus and rhesus data)

  • human volume of distribution at the steady state (Vd)

  • ratio of blood to human plasma (RBP_hum)

  • ratio of blood to plasma in rat (RBP_rat)

  • ratio of blood to plasma in mouse (RBP_mou)

  • ratio of blood to plasma in dog (RBP_dog)

  • ratio of blood to plasma in monkey (RBP_mky)

  • fraction unbound to human microsomes (fumic_hum)

  • fraction unbound to rat microsomes (fumic_rat)

  • fraction unbound to mouse microsomes (fumic_mou)

  • fraction unbound to dog microsomes (fumic_dog)

  • fraction unbound to monkey microsomes (fumic_mky)

  • fraction unbound to human hepatocytes (S+fuhep)

  • metabolic clearance mechanism (S+CL_Metab)

  • renal clearance mechanism (S+CL_Renal)

  • hepatic uptake clearance mechanism (S+CL_Uptake)

  • multi-class model of primary clearance mechanism: metabolic, renal, hepatic uptake (S+CL_Mech)

  • score used to designate primary clearance mechanism (ECCS_Risk and ECCS_Class)