Provided in the TissueDistributionDBs  and UniProt  databases. The determination of this feature depends upon a greater level of total protein (five ) distributed in a distinct tissue or perhaps a larger target concentration in that tissue than the average protein concentration. To explore the off-target collateral effect, the third feature was adopted, which can be the number of human similarity proteins. This was determined by counting the amount of equivalent proteins which can be outside the target protein loved ones for the studied drug target . This was calculated making use of BLAST similarity screening using the cutoff worth of evalue 0.005  for the human proteome system furnished within the UniProt database . The differential PAK6 custom synthesis expression in the target is the fourth function, that is capable of reflecting the expression variations of the P2X3 Receptor custom synthesis corresponding target in between diseased and healthier populations for particular diseases [74,889]. The expression data had been gathered from TTD  and calculated by using the HG-U133 Plus 2.0 platform which was determined by the Gene Expression Omnibus database . Collectively, these 36 attributes are worthwhile and meaningful in revealing human protein rotein interaction information for any offered target, like their connectivity, organization, robustness, and stability inside the human PPI network  plus the ontarget and off-target pharmacology of the studied targets [85,95]. These two aspects are important to enhancing potency for characterizing the underlying mechanisms of NTI drugs [2,96]. In preceding publications, like our previous analysis ,2. Components and methods 2.1. NTI drugs collection and linked targets and indications identification The NTI approved drugs and their related drug targets and indications have been obtained via the following measures. 1st, 1,921 FDA authorized drugs with their connected indications had been systematically collected and identified from the orange book in the US FDA . Then, all the corresponding diseases were standardized by the ICD-11 codes (the most recent version on the International Classification of Ailments) . Subsequent, the corresponding targets of your approved drugs were authorized by the therapeutic target database (TTD) , and 506 corresponding targets of your approved drugs had been confirmed. Third, a systematic literature critique of all these drugs was performed to confirm their TI value by looking the PubMedJ. Yin, X. Li, F. Li et al.Computational and Structural Biotechnology Journal 19 (2021) 2318Table 1 FDA authorized NTI drugs of cancer and cardiovascular disease with each other with their standardized indication, ICD-11 code, and target. ADRA1: Adrenergic receptor alpha 1; ADRA2: Adrenergic receptor alpha two; ADRB1: Adrenergic receptor beta-1; ADRB2: Adrenergic receptor beta-2; ADRB3: Adrenergic receptor beta-3; ATIII: Antithrombin-III; BCL-2: Apoptosis regulator BCL-2; F2: coagulation aspect II; F10: Activated coagulation factor X; DHFR: Dihydrofolate reductase; TOP1: DNA topoisomerase I; TOP2: DNA topoisomerase II; EGFR: Epidermal development factor receptor; ESR: Estrogen receptor; hDNA: Human deoxyribonucleic acid; IMPDH1: Inosine-50 -monophosphate dehydrogenase 1; IFNA2: Interferon-alpha 2; NET: Norepinephrine transporter; PDGFRB: Platelet-derived development aspect receptor; RET: Proto-oncogene c-Ret; RRM2: Ribonucleoside-diphosphate reductase M2; mTOR: Serine/threonine-protein kinase mTOR; SPT ATPase: Sodium/potassium-transporting ATPase; TMP1: Thymidylate synthase; TUB: Tubulin; c-Ki.