Drug Discovery Filtering

The simple structure-based filters integrated into JChem for Office are useful in the early phase of drug discovery to eliminate compounds, which will probably fall out on screening tests. These filters in general return TRUE, if a structure satisfies all filtering criteria.

The property names and filtering criteria are as follows:

LipinskiRuleof53of4

Returns TRUE if the molecule passes 3 of the following 4 criteria:

  • Molweight ≤ 500

  • LogP ≤ 5

  • Number of H-Donor atoms ≤ 5

  • Number of H-Acceptor atoms ≤ 10

LipinskiRuleof54of4

Returns TRUE if the molecule passes all of the following 4 criteria:

  • Molweight ≤ 500

  • LogP ≤ 5

  • Number of H-Donor atoms ≤ 5

  • Number of H-Acceptor atoms ≤ 10

Reference: Lipinski C.A.; et al; Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings.; Adv. Drug. Del. Rev.; 2001; 46, 3–26.

LeadLikeness

When designing leadlike combinatorial libraries, do not exceed the following property values:

  • Molweight: ≤ 450

  • LogD (on pH 7.4) ≥ -4 and ≤ 4

  • Number of Rings: ≤ 4

  • Number of Rotatable Bonds ≤ 10

  • Number of H-Donor atoms ≤ 5

  • Number of H-Acceptor atoms ≤ 8

Reference: Oprea, T.I. et al.; Is There a Difference between Leads and Drugs? A Historical Perspective; J. Chem. Inf. Comput. Sci., 2001, 41, 1308-1315.

GhoseFilter

  • Molweight ≥ 160 and ≤ 480

  • Number of Atoms ≥ 20 and ≤ 70

  • LogP between -0.4 and 5.6

  • Refractivity ≥ 40 and ≤ 130

Reference: Ghose, A. K. et al., A Knowledge-Based Approach in Designing Combinatorial or Medicinal Chemistry Libraries for Drug Discovery. 1. A Qualitative and Quantitative Characterization of Known Drug Databases. J. Comb. Chem., 1999, 1(1), 55-68.

MueggeFilter

  • Molweight ≥ 200 and ≤ 600

  • Number of Rings ≤ 7

  • Number of C Atoms ≥ 5 and (Number of Atoms-Number of C Atoms-Number of H Atoms) ≥ 2

  • Number of Rotatable Bonds ≤15

  • Number of H-Donor atoms ≤ 5

  • Number of H-Acceptor atoms ≤ 10

  • LogP ≥ -2 and ≤ 5

  • PSA ≤ 150

VeberFilter

Compounds, which meet only these two criteria will have a high probability of good oral bioavailability in the rat:

  • Number of Rotatable Bonds < 12

  • Polar Surface Area < 140 A²

Reference: Veber, Daniel F. et al; Molecular Properties That Influence the Oral Bioavailability of Drug Candidates, J. Med. Chem., 2002, 45(12), 2615-2623.

Bioavailability

  • Molweight ≤ 500

  • LogP ≤ 5

  • Number of H-Donor atoms ≤ 5

  • Number of H-Acceptor atoms ≤ 10

  • Number of Rotatable Bonds ≤ 10

  • Polar Surface Area ≤ 200

  • Number of Fused Aromatic Rings ≤ 5

This function works slightly differently if at least six from these criteria are TRUE for a molecule, then JCBioavailability returns TRUE, otherwise FALSE.