DrugMAP 2.0: molecular atlas and pharma-information of all drugs

Abstract

The escalating costs and high failure rates have decelerated the pace of drug development, which amplifies the research interests in developing combinatorial/repurposed drugs and understanding off-target adverse drug reaction (ADR). In other words, it is demanded to delineate the molecular atlas and pharma-information for the combinatorial/repurposed drugs and off-target interactions. However, such invaluable data were inadequately covered by existing databases. In this study, a major update was thus conducted to the DrugMAP, which accumulated (a) 20831 combinatorial drugs and their interacting atlas involving 1583 pharmacologically important molecules; (b) 842 repurposed drugs and their interacting atlas with 795 molecules; (c) 3260 off-targets relevant to the ADRs of 2731 drugs and (d) various types of pharmaceutical information, including diverse ADMET properties, versatile diseases, and various ADRs/off-targets. With the growing demands for discovering combinatorial/repurposed therapies and the rapidly emerging interest in AI-based drug discovery, DrugMAP was highly expected to act as an indispensable supplement to existing databases facilitating drug discovery, which was accessible at: https://idrblab.org/drugmap/.

Graphical Abstract

Figure 1.

An overview of this update of DrugMAP. In previous version, the molecular atlas was primarily composed of the pharmacokinetic data of medications (blue) and their interactions with three types of molecules: drug therapeutic target (DTT, orange), drug transporter (DTP, red), and drug-metabolizing enzyme (DME, green). In current version, DrugMAP was integrated with the combinatorial drug (CBD, strongblue), repurposed drug (RPD, skyblue), off-target effect of drug (DOT, purple) and disease (brown) information for all drugs.

Figure 2.

A typical CBD page showing combinatorial drug in DrugMAP. (A) general information of drug, such as drug name, synonyms and therapeutic class; (B) the list of CBDs containing this drug, at the top of this module, a heatmap of the normalized CBD synergy score is provided, the color of which was determined by the synergy score calculated from the HSA, Loewe, Bliss and ZIP models normalized via Min-Max Scaling; (C) detailed CBD page, opened by clicking on the CBD ID, provided details on the molecular atlas and the structures of the constituent drugs.

Figure 3.

A schematic illustration of repurposed drugs (RPD) and disease page in DrugMAP. (A) a typical RPD page provided the general information of drugs, and illustrated a list of repurposed diseases as well as the molecular atlas of RPD consisting of repurposed drugs; (B) a disease page, accessed by clicking on disease ID, which not only provided the name, definitions, and hierarchy of disease, but also described information about the mapping of the disease ontology to reputable existing databases. The molecular interaction atlas of the disease was also provided.

Figure 4.

A typical page of the drug's off-target (DOT) in DrugMAP. (A) the general information of each DOT; (B) the molecular atlas module of DOT, which not only provided a detailed list of drugs affected by the DOT and those drugs affecting the DOT and their modes of action, but also provided an interactive interaction network where the user could hover the mouse over the nodes and the interactions to view detailed information about the molecules and interactions.

Figure 5.

The schematic representation of the enriched pharma-information of drug in DrugMAP. (A) the general information of a medication, which included drug name, synonym, structure and so on; (B) a comprehensive list of diverse ADMET features of the drugs, providing an exhaustive description of the drug's 15 ADMET attributes such as absorption, bioavailability, clearance and so on, along with the corresponding literatures; (C) detailed information regarding the ADRs and ADR-associated DOTs of this particular drug.