“…The number of drugs exceeds the number of targets (Fig. 5 ), except for protein kinases, indicating a lack of selectivity among protein kinase inhibitors [ 19 , 30 , 31 ]. Fig.…”
Section: Drug Targets and Bioactivity Datamentioning
DrugCentral, accessible at https://drugcentral.org, is an open-access online drug information repository. It covers over 4950 drugs, incorporating structural, physicochemical, and pharmacological details to support drug discovery, development, and repositioning. With around 20,000 bioactivity data points, manual curation enhances information from several major digital sources. Approximately 724 mechanism-of-action (MoA) targets offer updated drug target insights. The platform captures clinical data: over 14,300 on- and off-label uses, 27,000 contraindications, and around 340,000 adverse drug events from pharmacovigilance reports. DrugCentral encompasses information from molecular structures to marketed formulations, providing a comprehensive pharmaceutical reference. Users can easily navigate basic drug information and key features, making DrugCentral a versatile, unique resource. Furthermore, we present a use-case example where we utilize experimentally determined data from DrugCentral to support drug repurposing. A minimum activity threshold t should be considered against novel targets to repurpose a drug. Analyzing 1156 bioactivities for human MoA targets suggests a general threshold of 1 µM: t = 6 when expressed as − log[Activity(M)]). This applies to 87% of the drugs. Moreover, t can be refined empirically based on water solubility (S): t = 3 − logS, for logS < − 3. Alongside the drug repurposing classification scheme, which considers intellectual property rights, market exclusivity protections, and market accessibility, DrugCentral provides valuable data to prioritize candidates for drug repurposing programs efficiently.
“…The number of drugs exceeds the number of targets (Fig. 5 ), except for protein kinases, indicating a lack of selectivity among protein kinase inhibitors [ 19 , 30 , 31 ]. Fig.…”
Section: Drug Targets and Bioactivity Datamentioning
DrugCentral, accessible at https://drugcentral.org, is an open-access online drug information repository. It covers over 4950 drugs, incorporating structural, physicochemical, and pharmacological details to support drug discovery, development, and repositioning. With around 20,000 bioactivity data points, manual curation enhances information from several major digital sources. Approximately 724 mechanism-of-action (MoA) targets offer updated drug target insights. The platform captures clinical data: over 14,300 on- and off-label uses, 27,000 contraindications, and around 340,000 adverse drug events from pharmacovigilance reports. DrugCentral encompasses information from molecular structures to marketed formulations, providing a comprehensive pharmaceutical reference. Users can easily navigate basic drug information and key features, making DrugCentral a versatile, unique resource. Furthermore, we present a use-case example where we utilize experimentally determined data from DrugCentral to support drug repurposing. A minimum activity threshold t should be considered against novel targets to repurpose a drug. Analyzing 1156 bioactivities for human MoA targets suggests a general threshold of 1 µM: t = 6 when expressed as − log[Activity(M)]). This applies to 87% of the drugs. Moreover, t can be refined empirically based on water solubility (S): t = 3 − logS, for logS < − 3. Alongside the drug repurposing classification scheme, which considers intellectual property rights, market exclusivity protections, and market accessibility, DrugCentral provides valuable data to prioritize candidates for drug repurposing programs efficiently.
“…The presence of kinases, as a major target class in ONP (absent for OFM drugs and poorly represented in OFP), can be explained by the relatively newer class of protein kinase inhibitors (approved after 1997) 28 showing poorer selectivity (among kinases) compared to other drug classes. 29 This leads, in many cases, to multiple MoA kinases linked to single drugs.…”
Section: ■ Data Sets For Drug Repurposingmentioning
confidence: 99%
“…OFM drugs are linked to only seven target classes (Figure a), of which three are representative (i.e., 84% of the total number of MoA targets): enzymes (110, 47%), ion channels (55, 24%), and GPCRs (31, 13%). The presence of kinases, as a major target class in ONP (absent for OFM drugs and poorly represented in OFP), can be explained by the relatively newer class of protein kinase inhibitors (approved after 1997) showing poorer selectivity (among kinases) compared to other drug classes . This leads, in many cases, to multiple MoA kinases linked to single drugs.…”
Section: Comparative Analysis Of the Ofp Onp And
Ofm Drugsmentioning
Drug
repositioning aims to reuse “old” drugs to treat
diseases outside their approved indication(s). Composition-of-matter
patents and FDA exclusivities can hinder the immediate availability
of some drugs to be repositioned (repurposed). Here, we analyze data
from the FDA Orange Book and use current on-market patent validity
and exclusivities to classify drugs into on-patent (ONP), off-patent
(OFP), and off-market (OFM) sets. In the absence of an unanimously
accepted definition for small molecules, these sets include organic
molecules and peptides with molecular weight between 100 and 1250,
which resulted in 237 ONP drugs, 320 OFM, and 996 OFP drugs, respectively.
We discuss the differences between the three categories in terms of
primary molecular properties, chemical diversity, mechanism-of-action
target classes, and therapeutic areas and comment on the enrichment
of OFP drugs in the near future. Given the intellectual property landscape,
and in the absence of specific property rights, we suggest that drugs
should be prioritized as follows, to improve the repositioning strategy:
(i) OFP, (ii) OFM, and (iii) ONP, respectively.
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