A recent study has described the new DrugCentral2021 database, which is a public resource that serves the scientific community by providing up-to-date information on active pharmaceutical ingredients.
DrugCentral
The DrugCentral database was first created in 2018 and integrates a broad spectrum of drug resources related to the chemical structures, biological activities, regulatory data, pharmacology and drug formulations. Since its creation in 2018, DrugCentral has strengthened its utility by being cross-referenced by resources such as UniProt and UniChem. The two published DrugCentral papers have been cited over 160 times and the databases accompanying website is accessed around 8,000 times a month, demonstrating its utility in the scientific community.
The recent study provides an update to the database, adding newly approved drugs by the FDA and EMA up to 31 March 2020. Drugs approved by the Japan Pharmaceuticals and Medical Device Agency (PMDA) were also monitored and added. Moreover, an important component of drug discovery and repositioning is understanding of a drug’s pharmacokinetic (PK) properties. In this regard, the researchers behind DrugCentral2021 introduced critically reviewed information on PK properties, thereby increasing the clinical pharmacology-related information coverage for drugs included in the database.
As evidenced by the COVID-19 pandemic, sudden outbreaks can rapidly impact global health. This pandemic has accelerated the need to rely on computational models capable of identifying and advancing novel therapeutics for clinical evaluation to speed up drug discovery. Therefore, the latest DrugCentral2021 update provides researchers with information on drug repositioning categories and machine learning models that are capable of predicting anti-SARS-CoV-2 activities to prioritize compounds against COVID-19.
Current Content of DrugCentral2021
The DrugCentral update includes the addition of 109 newly approved drugs and two molecules (mefuparib and EIDD-2801) with anti-SARS-CoV-2 potential to the original 4,531 that were indexed in 2018. Compared to the 2018 edition, the researchers observed an increase in the number of approved subtypes of biologics, such as antibody-drug conjugates (60% increase), oligonucleotides (50% increase) and monoclonal antibodies (30% increase). Moreover, around half of the drugs processed in this update were orphan drugs, highlighting the therapeutic gain in the group of rare diseases that has happened in the last couple of years.
The current update also adds 1,379 new bioactivity datapoints from ChEMBL and the Guide to Pharmacology. The researcher’s knowledge-based system sorts human proteins into four categories, according to their ‘target development level’ (TDL):
- Tclin are MoA-designated drug targets via which approved drugs act.
- Tchem are proteins that are not Tclin, but are known to bind small molecules with high potency.
- Tbio includes proteins that have Gene Ontology.
- Tdark, currently includes around 31% of the human proteome that were manually curated at the primary sequence level in UniProt, but do not meet any of the Tclin, Tchem or Tbio criteria.
Overall, DrugCentral2021 includes 669 Tchem, 219 Tbio and 14 Tdark proteins linked to 3859, 607 and 39 bioactivity points, respectively.
This update also included mapping new and existing drugs in DrugCentral into the latest versions of the World Health Organization Anatomic, Therapeutic and Chemical classification system (WHO ATC), the FDA Established Pharmacologic Class (EPC), the Medical Subject Headings (MeSH) and ChEBI pharmacological classifications using the researchers adaptive mapping schemes. Among novel drugs, 78 were linked to 136 pharmacologic classifications.
New data and functionality of DrugCentral2021
The current version of DrugCentral includes a recently published drug repositioning categorisation scheme, according to which drugs are sorted based on their market availability and rights according (repetition) the intellectual property. This scheme includes three distinct categories:
- OFP, or off-patent, which are on-market drugs with expired patents or exclusivities.
- ONP, or on-patent, which are on-market drugs covered by current patents and exclusivity protections.
- OFM, or off-market, which includes all previously marketed drugs that have been discontinued or withdrawn.
In total the researchers categorised 996 drugs as OFP, 320 as OFM and 237 as ONP. This classification scheme allows researchers to inform their decisions with respect to drug repositioning based on the existing intellectual property landscape.
The DrugCentral2021 update also includes nine measured properties that describe PK such as, absorption, distribution, metabolism, excretion and toxicity (ADMET). This data was termed ADMET-PK and was retrieved from five authoritative references.
Sex differences in adverse events were also in this update, since research has suggested that there is a sex bias in medical treatment. Creating an interface that highlights sex differences in adverse events may facilitate further analyses in this space, and may reveal essential drug actions to help pave the way for personalised medicine.
To aid in the investigation of the SARS-CoV-2 virus, the DrugCentral2021 update also included a web server named REDIAL-2020, which works to efficiently estimate anti-SARS-CoV-2 activities from molecular structure. This server contains a suite of machine learning models that represent various experimental assays related to live virus infectivity, viral entry and virus replication. It is hoped that this will support the process of drug discovery and repositioning for COVID-19.
Summary
DrugCentral2021 is an up-to-date public resource for drug discovery and repurposing. The new update increased existing datasets and also incorporated drug repositioning categories, ADMET-PK data, sex differences in adverse events as well as a server to aid COVID-19 drug discovery specifically. The researchers will continue to update the database as new drug regulatory approvals are published and they are planning to launch a chemical substructure and similarity search function within the next six months.
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