ChemGPS-VolSurf GPSVS in Clinical PK Property Modeling

ChemGPS-VolSurf (GPSVS) in Clinical PK Property Modeling 

We established [54] that, in conjunction with 2D-based descriptors, ChemGPS can provide global chemical space coordinates by performing extensive comparisons with GRID-based principal properties for heteroaromatic compounds [59], principal properties ( z-scores ) of a-amino acids [60], as well as by comparison to several local PCA models. The initial ChemGPS map turned out to be 9-dimensional [54]. 

FDA s biopharmaceutics classification system, BCS [5], serves as a guide for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms. BCS relies on two ADME properties, passive permeability and solu- 

GPSVS2 explains, to a lesser degree, water solubility. Because most efforts to model solubility have been focused on its relationship with logP [9], GPSVS2 was compared not only to Abraham s solubility dataset [32] (794 compounds), but also to the Pomona logP dataset [63] (7954 compounds). GPSVS2 scores correlated directly to measured logP values (P = 0.61), and to water solubility (P = 0.68). 

PGA models are usually interpreted by comparing descriptor loadings (their contribution) to the latent variables, which relate to physical meaning. However, in GPSVS, the first two components are directly related to measured properties. 

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