Today, we released P&D 02.2021 with several major updates including our brand new P&D probe-likeness score integrated together with scores from Probe Miner and Chemical Probes Portal, total redesign of the compound detail view, and two new focused compound sets.
P&D probe-likeness score (PDP score) is a value, ranging from 0 to 100%, calculated for compounds labelled as probes for each of their directly annotated human target of interest (if specified). It consists of 6 parameters (partial scores): potency, selectivity, cell-potency, control compound, orthogonal probe and structural alerts, and a synergy part of the score. Finally, the PDP score is simply a sum of all of its parts. If a PDP score for a compound-target pair is larger than 70% (not equal or larger, but LARGER), the compound is labelled as P&D approved. The score is designed in a way that the 70% threshold can't be surpassed if the compound is not potent, cell-potent on target and selective at the same time. You can easily filter all P&D approved chemical probes using the P&D approved tag. If you want to know the exact setting of the PDP score and its parameters, you can find it in the FAQ section.
However, PDP score is not the only probe score you can find at the P&D portal. From the current version, we also integrated the Probe Miner score (PMI score) and Chemical Probes Portal Ratings for use in cells (CPO cells) and organisms (CPO organisms). For better comparability, all score values are normalized to range from 0% to 100%, e.g., 3 out of 4 stars in CPO ratings is converted to 75%. All integrated scores can be easily used to filter/order compounds by clicking on the score or through the search field. For example, to filter all probes with at least 3 out of 4 stars at Chemical Probes Portal with P&D approved probes is as simple as this. Since there can be multiple multiple values for PMI and PDP scores, evaluating each target pair separately, the highest of these values for each compound is used for filtering needs.
The compound detail pages went through a total redesign to include all data associated with the compound with a focus on probe/probe-like compounds. Apart from sections all compound detail pages share, such as targets, compound sets and external links, chemical probe pages include probe-specific sections including probe scores, control compound, orthogonal probes (probes for the same target/s not sharing the same scaffold with structural similarity up to 40%) ordered by their PDP score and similar probes (probes for the same target not in orthogonal probes).
Apart from all major data sources being updated to their last versions (ChEMBL 28, Guide to Pharmacology 2021.1 or DrugBank 5.1.8) and many updated compound sets, we also added two brand new focused compound sets to our collection: IPPI - DB and Nuisance compounds in cellular assays.
IPPI - DB (Inhibitors of Protein-Protein Interaction Database), developed and maintained at Institut Pasteur, is a database of modulators of protein-protein interactions. It contains exclusively small molecules and therefore no peptides. The data are retrieved from the literature either peer-reviewed scientific articles or world patents.
Nuisance compounds in cellular assays is a set of compounds extracted from a paper of the same name published by Jayme L. Dahlin in Cell Chemical Biology in Feb 2021. The supplemental information contained a set of more than 1,200 compounds that exhibit assay interference or undesirable mechanisms of bioactivity (“nuisance compounds”) that are routinely encountered in cellular assays, including phenotypic and high-content screening assays. Apart from the set itself, we also systematically integrated different "nuisance" classes into our structural alerts. They can be now easily used to filter compounds tagged as luciferase inhibitors, tubulin modulators, compounds optically interfering with the assay, and many others.
As the last thing, we also added two new sources to our external links. First, we added links to the COCONUT database (COlleCtion of Open Natural Products) which is an open-source project for Natural Products (NPs) storage, search and analysis, combining data from more than 50 open natural product resources. Second, we used a set of in-stock compounds kindly provided to us by Chemspace (the largest online catalogue of small molecules) to link to this resource and also to tag all matched compounds in P&D as available (we also use data from Mcule, MolPort and up-to-date commercial compound sets).
We hope you find the new data and features useful, and if you have any suggestions for new functions or compound sets we could integrate into our database, please, let us know through the contact form or through our Twitter account (@probesanddrugs).