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. 2021 Jul 16;12(8):1428-1441.
doi: 10.1039/d1md00138h. eCollection 2021 Aug 18.

Will the chemical probes please stand up?

Ctibor Škuta  1 , Christopher Southan  2 , Petr Bartůněk  1
Affiliations

Will the chemical probes please stand up?

Ctibor Škuta et al. RSC Med Chem. .

Abstract

In 2005, the NIH Molecular Libraries Program (MLP) undertook the identification of tool compounds to expand biological insights, now termed small-molecule chemical probes. This inspired other organisations to initiate similar efforts from 2010 onwards. As a central focus of the Probes & Drugs portal (P&D), we have standardised, integrated and compared sets of declared probe compounds harvested from 12 different sources. This turned out to be challenging and revealed unexpected anomalies. Results in this work address key questions including; a) individual and total structure counts, b) overlaps between sources, c) comparisons with selected PubChem sources and d) investigating the probe coverage of druggable targets. In addition, we developed new high-level scoring schemes to filter collections down to probes of higher quality. This generated 548 high-quality chemical probes (HQCP) covering 447 distinct protein targets. This HQCP collection has been added to the P&D portal and will be regularly updated as established sources expand and new ones release data.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Physico-chemical properties distribution (top: molecular weight, middle: calculated log P, bottom: TPSA) for experimental probes (blue), calculated probes (orange) and small-molecule approved drugs set from ChEMBL (green) (x: property range, y: compounds percentage). The properties were calculated by RDKit.
Fig. 2
Fig. 2. The number of associated targets for probes (blue) and the small-molecule approved drugs set from ChEMBL (green) (x: axis number of targets, y: compounds percentage). Only compounds with at least one associated target were included encompassing 4257 probes and 2005 approved drugs.
Fig. 3
Fig. 3. A bar chart showing the target families distribution separately for all (green), experimental (blue) and calculated (orange) probes (x: target family, y: number of targets). The assignments are based on the ChEMBL and Guide to Pharmacology target classification.
Fig. 4
Fig. 4. Venn diagram of P&D targets against selected human UniProt cross-references and two Pharos TDLs.
See this image and copyright information in PMC

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