ADCdb: the database of antibody-drug conjugates

Abstract

Antibody-drug conjugates (ADCs) are a class of innovative biopharmaceutical drugs, which, via their antibody (mAb) component, deliver and release their potent warhead (a.k.a. payload) at the disease site, thereby simultaneously improving the efficacy of delivered therapy and reducing its off-target toxicity. To design ADCs of promising efficacy, it is crucial to have the critical data of pharma-information and biological activities for each ADC. However, no such database has been constructed yet. In this study, a database named ADCdb focusing on providing ADC information (especially its pharma-information and biological activities) from multiple perspectives was thus developed. Particularly, a total of 6572 ADCs (359 approved by FDA or in clinical trial pipeline, 501 in preclinical test, 819 with in-vivo testing data, 1868 with cell line/target testing data, 3025 without in-vivo/cell line/target testing data) together with their explicit pharma-information was collected and provided. Moreover, a total of 9171 literature-reported activities were discovered, which were identified from diverse clinical trial pipelines, model organisms, patient/cell-derived xenograft models, etc. Due to the significance of ADCs and their relevant data, this new database was expected to attract broad interests from diverse research fields of current biopharmaceutical drug discovery. The ADCdb is now publicly accessible at: https://idrblab.org/adcdb/.

Graphical Abstract

Figure 1.

A typical webpage showing the general information of ADC (trastuzumab deruxtecan). Diverse pharma-information were provided, which included: ADC name, ADC synonym, aimed disease and the corresponding clinical status, ADC structures (downloadable in 2D & 3D format), key ADC components (antibody, linker & payload), the antigen of antibody, the target of payload, antibody-linker conjugate type, linker-payload combination type and a variety of external links to established molecular biological databases (PubChem, DrugMAP, TTD, DrugBank, etc.).

Figure 2.

A comprehensive set of pharma-information for studied ADC. First, the detailed ADC data were described, which included: aimed disease indications together with their corresponding clinical status, ADC’s structure describing antibody, linker and payload, diverse clinical response data (such as the clinical detail of both ADC and enrolled patient, the reported ADMET properties of ADC, administration dosages, reported adverse drug reactions and clinical primary endpoints), drug-antibody ratio of ADC, etc. Second, the pharma-information of the key components of each ADC was explicitly illustrated. (a) the pharma-information of corresponding antibody included: antibody sequence, targeted antigen, tissue-specific antigen abundances, various pharmaceutical data of this antibody (disease, clinical status, brand name, developing company); (b) the pharma-information of corresponding linker contained: linking strategies (cleavable/uncleavable), those linkers conjugated to antibody; (c) the pharma-information of payload covered: the target of any studied payload, diverse payloads conjugated to studied antibody and the drug-like properties of studied payloads (such as: molecular weight, topological polar surface area, rotatable bond count, hydrogen bond donor count and hydrogen bond acceptor count).

Figure 3.

A typical page describing the activity outline of ADC (trastuzumab deruxtecan). Such activity data included: objective response rates (ORRs) and complete remissions (CRs) of ADCs in different stages of clinical trial, inhibition levels and growth delays of ADCs in diverse disease PDX models/cell lines and half maximal inhibitory concentrations of ADCs in different disease cells. The specific activity values of ‘trastuzumab deruxtecan’ were provided, together with the corresponding activity type, unit and experimental labels (such as NCT number, PDX name, cell line and disease model), and the detailed information underlying these activities could be further accessed by simply clicking on those provided hyperlinks.

Figure 4.

A typical webpage offering the activity details of ADC (trastuzumab deruxtecan). Such activity data included: efficacy information of ADC, the clinical status, primary endpoint, patient enrollment information of the clinical study of ADC, the reported adverse drug reactions of ADC, etc. Various experimental details were also provided based on the original publications.

Figure 5.

The activity information of ADC’s key components (antibody & payload). The activity detail of an exemplar antibody (trastuzumab) was described (the binding affinity of this antibody on its antigen), and its therapeutic mechanism together with the experimental method applied to measure its antigen affinity were also systematically provided. Meanwhile, activity details of the exemplar payload (monomethyl auristatin E) were also provided. Under each activity datum, the corresponding experimental validation method (including various cell lines, diseased models and experimental details) were described. The detailed information underlying these activities could be further accessed by simply clicking on those provided hyperlinks.

Figure 6.

A typical antigen-centric panorama (using ERBB2 as an example) for establishing the correlations between diverse ADCs and different components combinations. The antigen ERBB2 was first linked to a list of its binding antibodies (indicated by ‘Y’ shape in blue color), and these linked antibodies were then connected to their resulting ADCs (denoted by the ADC icon colored by both blue and orange; which were further linked to the corresponding payload highlighted in orange and placed in the outermost layer). By placing the mouse on any of the antibodies, ADCs and payloads, their introduction would be retrieved (the name of selected antibody/ADC/payload, the isotype & antigen of studied antibody, the indication & linker of selected ADC, the targets & structure of studied payload, etc.).