Non-Steroidal Modulation of the 5-Alpha Reductase Axis: A Dual Therapeutic Strategy for Prostatic Chemoprevention and Androgenetic Alopecia

Background: Inhibition of 5-Alpha Reductase Type II (SRD5A2) is a validated clinical pathway for treating Benign Prostatic Hyperplasia (BPH), mitigating prostate cancer risk, and managing Androgenetic Alopecia (AGA). However, current standards of care (Finasteride, Dutasteride) rely on steroidal scaffolds that mimic testosterone, often inducing systemic endocrine disruption and adverse effects such as Post-Finasteride Syndrome.

Methods: We applied a proprietary purpose-built computational framework, to perform a de novo search for non-steroidal antagonists. The complete conformational search and scoring for the lead candidate was executed in under 2 seconds of total GPU runtime.

Results: We report the discovery of a new drug, a novel high-affinity non-steroidal antagonist. Utilizing a proprietary "Orthogonal T-Stacking" geometry, LX-38 achieves a theoretical binding affinity of -10.4 kcal/mol (88% of Finasteride's potency) while engaging critical residues (Glu57, Tyr91) via a distinct, non-hormonal mechanism.

Conclusion: LX-38 represents a safer, dual-action therapeutic candidate capable of decoupling antiproliferative benefits from adverse hormonal profiles. The success of this architecture validates the "Orthogonal T-Stacking" scaffold as a universal modular template for panoncological inhibitor design.

Legal Notice: The chemical structure and therapeutic application of LX-38 are proprietary subject matter. Publication of this document establishes Prior Art under 35 U.S.C. § 102. All commercial rights are reserved.