Leading Edge Predictors for Drug Discovery

CSLogWS Home

CSLogD Home

CSLogP Home

CSpKa Home

CSBBB Home

CSPB Home

CSGenoTox Home

CSHIA Home

Download a Pre-print
about CSHIA

CSHIA

     ...Dataset Profile

Dataset Used in Generating the CSHIA Model

Sources for Experimental Oral Absorption Values:


The percent human intestinal absorption (%HIA, oral absorption) values and associated drugs structures used in the generation and testing of the CSHIA predictor were taken from the sources given in the list below.  Drugs which are believed to undergo active or facilitated transport were removed from consideration and were not used for either model development or validation.   The members of the tetracycline family are an exception and were included in the dataset even though they are suspected to undergo carrier-mediated transport. The tetracyclines were included because their participation in active transport mechanisms has not been experimentally demonstrated.  Nonetheless, all drugs from different sources with reported values were compared. In the vast majority of cases(98%) reported or used % oral absorption values among the sources were in excellent agreement for drugs undergoing passive transport.


    (1) Zhao Y. H. et al, J. Pharm. Sci. 90, 749 (2001)

    (2) Zmuidinavicus D. et al, J. Pharm. Sci. 92, 621 (2003)

    (3) Klopman G. et al, Eur. J. Pharm. Sci., 17, 253 (2002)

    (4) PDF (Physician Desk Reference), Publ. Thompson (2003)

    (5) Dolly C. Ed., Therapeutic Drugs, 2nd Ed, Publ. Churchill Livingstone (1999)

CSHIA Compound Profile

Drug like / non-drug like designations:


The drug compound profiles given below are for the commercially available drugs used in CSHIA development and testing.  425 drugs were used in model development and 203 drugs for external validation testing.  The average value for sum of the H-bond donors and acceptors was approximately eight (8) with 82% of the drugs with their sum less than or equal to ten (10).  The range of the donor-acceptor sum was from 1 to 59. 


(see CSpKa Dataset Profile for an explination of the, "Rule of Fives")


The predominant structural feature in the training set is the aromatic ring system, followed by unsaturated N-heterocyclic systems. Both types of ring systems are associated with fused ring formations in the majority of compounds.


A table of compound heterogeneity and plots of the major groups and ring types are given below.

CSHIA  Representative Compounds

Follow the link below to a set of 30 representative compounds of the 203 used in external validation testing of CSHIA.  Each structure is given along with a comparison of known experimental values and their predicted % oral absorption value from external validation.

Go to: CSHIA  Compounds

Back to: CSHIA  Home Page

search
links
user login
contact us

To contact us:

Phone: (888) 636-8777

Fax: 781-275-5197

Email:  sales@chemsilico.com

Copyright © 2003 ChemSilico LLC All Rights Reserved

Terms and Conditions of Use | Privacy Policy

ChemSilico is a registered trademark of ChemSilico LLC, Tewksbury, MA 01876