SRD5A1 (Steroid 5 Alpha-Reductase 1)

Pharmacovigilance and clinical reports show that a subset of patients treated with finasteride or dutasteride may experience persistent psychiatric and sexual adverse effects, known as post-finasteride syndrome. The current findings underscore the need for careful patient counseling, systematic monitoring, and further translational studies integrating genetics, neuroendocrine markers, and standardized psychiatric outcomes to identify individuals at risk and advance personalized medicine in this field.

Thus, SRD5A2 has clinical relevance in BPH, prostate cancer and other androgen-mediated conditions. However, limitations of SRD5A2-targeted therapies need to be overcome for future strategies to enhance the efficacy of 5ARI-based treatments.

Bioinformatic analysis revealed that SRD5A1, a critical enzyme in androgen metabolism, is downregulated by the BRD4 inhibitor JQ1. This finding was validated using I-BET151, another BRD4 inhibitor, which also suppressed SRD5A1 expression in PCa cell lines. Furthermore, treatment with dutasteride (Duta), an SRD5A family inhibitor, significantly reduced both cell proliferation and invasion...Co-administration of BRD4 and SRD5A1 inhibitors yielded a more pronounced suppression of AR expression. These findings highlight the pivotal role of SRD5A1 in PCa progression and suggest that combinatorial inhibition of BRD4 and SRD5A1 may provide a more effective strategy for attenuating AR expression and halting disease development.

ADMET predictions indicated low oral bioavailability and potential CYP2D6 interactions. While DDAs show promise as SRD5A1 inhibitor scaffolds, their primary environmental presence as disinfectants necessitates caution regarding endocrine disruption risks.

Our findings suggest that alkaloids in TWP may exert multi-target synergy to disrupt key survival pathways driving cisplatin resistance in ovarian cancer. These mechanistic insights not only rationalize its observed anti-tumor activity but also support its potential clinical repurposing from an approved anti-inflammatory drug to an oncology therapeutic.

PAH appears to inhibit CRC by targeting SRD5A1, thereby promoting autophagy through the PI3K/AKT pathway. This offers new perspectives for both the diagnosis and treatment of CRC.

3D-QSAR modeling identified hydrophobic features as critical for inhibition, while correlation analyses confirmed relationships between inhibitory potency and carbon length (C3-C12) and hydrophobicity properties. These findings provide structural insights for developing selective SRD5A1 modulators with potential applications in neuropsychiatric disorders.

Additionally, dichlorooctylisothiazole showed significant inhibition of rat SRD5A1 with an IC50 of 21.47 μM. In conclusion, these findings reveal some isothiazole disinfectants as potential endocrine disruptors targeting neurosteroid biosynthesis via SRD5A1 and highlight clear structure-activity relationship and species-dependent variance.

Both β-sitosterol and 2 demonstrated substantial inhibitory effects of these enzymes for dihydrotestosterone formation and significantly reduced cell viability, highlighting their therapeutic potential. These findings enhance our understanding of the inhibitory effects of β-sitosterol and 2 on LNCaP cells and suggest their promising application in the treatment of prostate cancer.

Hormonal cluster #1 or #3 is an independent prognostic factor regarding poor progression-free survival. Hormonal cluster assignment also affects the predicted drug response with cluster-dependent susceptibility to specific novel therapeutic compounds.

Integrating regulatory information with gene expression improved early versus late-stage prediction. The identified potential prognostic and diagnostic biomarkers in this study may guide us in developing effective therapeutic strategies for CRC management.

3D-QSAR revealed the importance of hydrophobic aromatic regions in SRD5A1 binding. This study delineates the inhibitory effects of salicylates and binding mechanisms on human and rat SRD5A1, providing insights into their impact on neurosteroid production.