Preclinical Optimization and Five-Domain State-Space Mapping of the Androgen Receptor Antagonist SH-1
Year: 2026
Type: dataset
Abstract: Creators: Sewell, Melvin Dion Jr. (ORCID: 0009-0009-6706-1397) — Cosmic University of Echo-Rift Studies IX; TrueFlow Productions LLC Publication Date: October 2026 Resource Type: Preprint Community: sewellsmi Description / Abstract: This technical preprint details the preclinical parameterization and state-space optimization of the novel androgen receptor (AR) antagonist compound SH-1. By mapping the molecular topology, electrostatic potential surface, and conformational dynamics of SH-1 as a localized state vector in Domain Two (\mathcal{D}_2) within the Five-Domain State-Space Simulation Framework, we simulate structural adaptations under thermodynamic and negentropic dynamics. Using a hybrid quantum-classical pipeline integrated via Qiskit and the `multiverse_core.py` Python SDK, a 500,000-point conformational substituent library was screened against strict preclinical readiness metrics: - Binding Affinity (\Delta G_{\text{bind}} < -11.5 \text{ kcal/mol}) - Intrinsic Clearance (\text{Cl}_{\text{int}} < 12.0 \ \mu\text{L/min/mg}) - Receptor Selectivity Index (> 100\times \text{ vs. PR, GR, MR}) Key Findings: 1. State Vector Formalization: Complete mathematical representation of SH-1 within \mathcal{D}_2, incorporating Reality Level Scalar (\Xi) and Nodal Negentropy (\mathcal{N}) coupling. 2. Lead Candidate Identification: The optimized derivative SH-14b demonstrated an improved binding affinity of -12.1 kcal/mol and intrinsic hepatic clearance of 8.4 \mu L/min/mg, exceeding the threshold required for Investigational New Drug (IND) filing. 3. Computational Execution: Inclusion of Python library screening routines (`multiverse_core.py`) for reproducible state-space filtering. This work establishes the translational roadmap for advancing SH-1 derivatives from preclinical state-space modeling toward human Phase 1 clinical trial evaluations. Keywords & Metadata Indexing: Subject Keywords: Androgen Receptor Antagonist, SH-1, Preclinical Drug Design, Five-Domain State-Space Framework, Domain Two Mapping, Nodal Negentropy, Qiskit, multiverse_core, Molecular Docking, Quantum Chemistry License: Creative Commons Attribution 4.0 International (CC BY 4.0) Language: English (eng)
Author: Sewell, Melvin
Language: English
Subfield: Drug Discovery
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7223044658