Wombat

News Clippings, Motoring Channel Staff, Web Wombat, 11 February, 2005. 

Common wombat, Vombatus ursinus 0.15 (95% Cl of 0.12-0.19) mg/kg BW LD50, free-ranging 11... 

In an effort to understand if HAMs are, in any way, different from LAMs (low activity molecules), we extended this survey to compounds published between 1991 and 2002, as indexed in WOMBAT [26]. This database [27] contains 4927 unique structures with at least one measured activity better than 1 nM (HAMs), and 34028 unique structures with at least one activity less than 1 XM (LAMs). Between HAMs and LAMs, 1080 molecules are common, that is, they have at least one activity above 1 nM and at least one activity below 1 XM. This is not uncommon for, for example, highly selective molecules. We did not exclude these from either set since we monitor trends, not exact figures. We studied these trends using 2-D-(two-dimensional) descriptors, that is, descriptors that do not use information related to the three-dimensional characteristics of model compounds. These descriptors can be classified as follows ... 

To further investigate the qualities of small, but active compounds, we performed a query in WOMBAT [26] for molecules with activity better than 10 nM and MW < 200. 

By applying the results from Table 2.3 to the work presented in Tables 2.1 and 2.2, we can further examine the proportion of high-activity and low-activity molecules with leadlike properties, that is, MW < 460, LogP —4 to 4.2, ELogSw > —5, RTB < 10, RNG < 4, HDO < 5 and HAG < 9 [62]. There are 21.7% HAMs and 41% LAMs that meet the computational leadlike criteria (Table 2.4). The probability of finding HAMs in WOMBAT is rather low in the leadlike space, and is higher outside the R05-compliant space (see Hi/Lo ratios in Table 2.4). While this may not hold true across all chemical space, it does strengthen the conclusion that HAMs are decorated with... 

Fig. 2.4 Biological activity versus ELogP for four targets from WOMBAT S-HTja [N = 2306), /x-opioid (N = 1202), dihydrofolate reductase (DHFR, N = 2351) and phosphodiesterase 4 (PDE4, N = 1221). The numbers indicate the amount of data points visible in each plot the X-axis is ElogP, and the Y-axis combines K and IC50 values in inverse logio units.

I., Banda, M., Simon, Z., Mracec, M., Oprea, T.I. WOMBAT World of molecular bioactivity. In Chemoinform-atics in Drug Discovery, Oprea, T.I. 

WOMBAT 2004.1 is available from Sunset Molecular Discovery, Santa Fe, New Mexico,... 

I 9 WOMBAT World of Molecular Bioactivity Tab. 9.1 Examples of annotated databases... 

Fig. 9.1 Bioactivity distribution pie charts in WOMBAT 2004.1, classified by target type. The size of the pie chart is proportional to the representation of each target class in the database.

Example 1. A question that arises often in preclinical pharmaceutical research is how well does an observed biological activity measured in animals match the same activity in humans. WOMBAT 2004.1 contains 29 263 entries with human as the biological species and 27 229 entries as rat . Their intersection, 2339 records, contains measurements from the same research groups, as the query selects only records where only human and rat activities were reported in the same paper. After trimming the dataset to force the same target and the same activity type (e.g., Kj or IC50), we are... 

Tab. 9.4 Rat versus human bioactivity data comparison using entries from WOMBAT.2004.1 N is the number of compounds, R is the correlation coefficient, and is the fraction of explained variance...

Being an annotated database, WOMBAT continues to evolve in time - not only with the addition of more entries but also with updates and restructuring of the biological and chemical information, which is subject to change even after the data is captured. The... 

---