Page 169 - EJMO-9-2

Eurasian Journal of
Medicine and Oncology Genetic insights into CAD drug targets

proteins. In this PPI network, TNF, LPL, FES, and DHX36 3.10. Molecular docking
have multiple interaction pathways with other proteins, To further evaluate the binding interactions between
indicating their central roles in the network. For the PPI the candidate target genes and the predicted drugs, we
network constructed using GeneMANIA, in addition to performed a molecular docking analysis (Figure 7). The
the four core genes, the network also included 20 potential results indicated that all small molecule compounds
interacting genes (Figure 6B). Functional analysis of this were able to enter the binding domains of the target
network demonstrated that these genes play important proteins, with binding energies ranging from −4.9684 to
roles in metabolism and immune regulation, consistent −7.3132 kcaL/moL (Table 4). Notably, the lovastatin–FES
with previous enrichment analysis results, further complex (−7.3132 kcaL/moL) and the (3s)-3-cyclopentyl-
confirming their potential mechanisms in diseases such as 6-methyl-7-[(4-methylpiperazin-1-Yl)sulfonyl]-3,4-
CA. dihydro-2h-1,2,4-benzothiadiazine 1,1-dioxide–DHX36
complex (−7.0794 kcal/mol) demonstrated, particularly
3.9. Candidate drug prediction low binding energies, indicating highly stable interactions.
We utilized the DSigDB database to predict potential drugs
for the candidate target genes, adjusting p-values to list the 4. Discussion
top 20 drugs (Table 3). Alendronate and lovastatin emerged The development of novel therapeutic drugs for CA faces
as significant compounds associated with FES, whereas numerous challenges, primarily due to the incomplete
stearic acid and IBMX were identified as important drugs understanding of the disease’s underlying mechanisms.
related to TNF and LPL. Furthermore, (3s)-3-cyclopentyl- In this study, we identified nine druggable genes that may
6-methyl-7-[(4-methylpiperazin-1-Yl)sulfonyl]-3,4- influence CA outcomes based on various druggability
dihydro-2h-1,2,4-benzothiadiazine 1,1-dioxide was analyses. Among them, four genes (DHX36, FES, LPL,
recognized as a key compound linked to DHX36. and TNF) demonstrated strong evidence of colocalization

Table 3. Candidate target prediction of the top 20 drugs
Drug names p Adjusted p Target genes
Lovastatin (Boss Pharma) 0.000 0.002 FES; LPL; TNF
Alendronate sodium (Boss Pharma) 0.000 0.019 FES; TNF
Cerivastatin (Boss Pharma) 0.000 0.019 FES; LPL; TNF
Simvastatin and niacin (Boss Pharma) 0.000 0.019 FES; LPL; TNF
Stearic acid (Boss Pharma) 0.000 0.019 LPL; TNF
(-)-Epigallocatechin gallate (Boss Pharma) 0.000 0.019 FES; LPL; TNF
IBMX (Boss Pharma) 0.000 0.020 LPL; TNF
Artemisinin (Boss Pharma) 0.000 0.020 FES; TNF
Nicotinic acid (Boss Pharma) 0.000 0.020 LPL; TNF
Mevalonic acid (Boss Pharma) 0.000 0.020 FES; TNF
22-Hydroxycholesterol (CTD 00000121) 0.000 0.020 LPL; TNF
MK 886 (CTD 00002517) 0.000 0.021 LPL; TNF
Zoledronic acid (Boss Pharma) 0.000 0.021 FES; TNF
Picrotoxinum (Boss Pharma) 0.000 0.021 FES; TNF
Orlistat (CTD 00002339) 0.000 0.021 LPL; TNF
(3s)-3-Cyclopentyl-6-methyl-7-[(4-methylpiperazin-1-Yl) sulfonyl]-3,4-dihydro-2h-1,2,4-benzothiadiazine 0.000 0.021 DHX36; TNF
1,1-dioxide (Boss Pharma)
Coenzyme A (Boss Pharma) 0.000 0.021 FES; LPL
Benzbromarone (CTD 00005480) 0.000 0.021 LPL; TNF
T0901317 (CTD 00003912) 0.000 0.021 LPL; TNF
Beta-carotene (Boss Pharma) 0.000 0.021 FES; TNF
22-Hydroxycholesterol (CTD 00000121) 0.000 0.020 LPL; TNF

Volume 9 Issue 2 (2025) 161 doi: 10.36922/ejmo.7387