Prostate cancer refers to uncontrolled abnormal cell growth (Cancer) within the prostate gland. The disease is a rising health concern and accounts for 3.8% of all cancer deaths globally. Uganda has one of the highest incidence rates of the disease in Africa being 5.2% and many of the diagnosed patients are found to have advanced stage prostate cancer. This study aimed to use STEAP2 protein (prostate cancer specific biomarker) for the discovery of new lead compounds against prostate cancer. To determine the most likely compound that can bind to STEAP2 protein, we docked the modelled STEAP2 3 Dimension structure against 2466 FDA (Food and Drug Administration) approved drug candidates using Autodock vina. Protein Basic Local Alignment Search Tool (BLASTp) search, Multiple Sequence Alignment (MSA), and phylogenetics were further carried out to analyse the diversity of this marker and determine its conserved domains as suitable target regions. Six promising drug candidates (ligands) were identified of which Triptorelin had the highest binding energy (-12.1 kcal/mol). Leuprolide was the second most promising candidate with a docking energy of -11.2 kcal/mol. All the top 3 of 6 drugs interacted with highly conserved residues Ser-372 and Gly-369 in close proximity with the iron binding domain that was shown to be important for catalysis of metal reduction. The two drugs had earlier been approved for treatment of advanced prostate cancer but with an elusive mode of action. Thanks to this study we now have an insight on how their interaction with STEAP2 might be important during treatment.

Prostate cancer is a rising health concern and accounts for 3.8% of all cancer deaths globally. Uganda has one of the highest incidence rates of the disease in Africa at 5.2% with the majority of diagnosed patients found to have advanced disease. This study aimed to use the STEAP2 protein (prostate cancer–specific biomarker) for the discovery of new targeted therapy. To determine the most likely compound that can bind to the STEAP2 protein, we docked the modeled STEAP2 3D structure against 2466 FDA (Food and Drug Administration)-approved drug candidates using AutoDock Vina. Protein basic local alignment search tool (BLASTp) search, multiple sequence alignment (MSA), and phylogenetics were further carried out to analyze the diversity of this marker and determine its conserved domains as suitable target regions. Six promising drug candidates (ligands) were identified. Triptorelin had the highest binding energy (−12.1 kcal/mol) followed by leuprolide (docking energy: −11.2 kcal/mol). All the top two drug candidates interacted with residues Ser-372 and Gly-369 in close proximity with the iron-binding domain (an important catalyst of metal reduction). The two drugs had earlier been approved for the treatment of advanced prostate cancer with an elusive mode of action. Through this study, further insight into figuring out their interaction with STEAP2 might be important during treatment.