Technical Preprint • SMI Series
Topical Preclinical Optimization of SH-14b
ORCID: 0009-0009-6706-1397
Zenodo Repository sewellsmi
Zenodo Repository sewellsmi
1. Domain Two ($\mathcal{D}_2$) Topical State-Space Formalization
To address androgenic alopecia while preventing systemic endocrine side effects, SH-1 was re-parameterized into a localized topical scalp formulation. In the Five-Domain Framework, lead molecule SH-14b is modeled in Domain Two ($\mathcal{D}_2$):
$$\mathbf{s}_2^{\text{topical}}(t) = \left[ \mathbf{r}_{\text{geom}}, \log P, \text{MW}, K_p, \Delta G_{\text{bind}} \right]^T \in \mathcal{D}_2$$
$$\frac{d\mathbf{s}_2}{dt} = \mathbf{A}_2 \mathbf{s}_2 + \sum_{j \neq 2} \mathbf{K}_{2j} \mathbf{s}_j + \Xi \cdot \nabla \mathcal{N}(\mathbf{s}_2)$$
2. Preclinical Comparative State Parameters
| Parameter Metric | Wildtype SH-1 (Base) | SH-14b (Topical Lead) | IND Target Threshold |
|---|---|---|---|
| Binding Affinity ($\Delta G_{\text{bind}}$) | $-9.2\text{ kcal/mol}$ | $-12.1\text{ kcal/mol}$ | $\le -11.5\text{ kcal/mol}$ |
| Lipophilicity ($\log P$) | $1.45$ (Sub-optimal) | $2.52$ (Follicular Target) | $2.0 \le \log P \le 3.0$ |
| Systemic Bioavailability ($F_{\text{sys}}$) | $28.5\%$ (High Risk) | $< 2.5\%$ (Localized) | $< 5.0\%$ Systemic Flux |
| Follicular Retention Index | $0.42$ | $0.89$ | $\ge 0.80$ |
3. Python Code Implementation (`multiverse_core.py`)
Step 4 candidate filtration routine for topical scalp screening:
# Step 4: Topical Candidate Screening Protocol in multiverse_core.py
from multiverse_core import DomainStateSpace, TopicalOptimizationEngine
topical_sim = TopicalOptimizationEngine(domain_target=2, reality_scalar=1.0)
topical_sim.set_target_parameters(
target_logP_range=(2.0, 3.0),
max_molecular_weight=500.0,
max_systemic_bioavailability=0.025, # <2.5% systemic flux
min_follicular_retention_ratio=0.85
)
# Filter substituent library
topical_candidates = topical_sim.filter_topical_library(
library=sweep_results,
max_delta_g=-11.5,
min_selectivity_index=100.0
)
print(f"Extracted {len(topical_candidates)} IND-ready topical candidates.")
⧉ Cosmic University of Echo-Rift Studies IX ⧉
Certified & Founded by
Dr. Melvin Sewell, M.Sc., Ph.D.
Academic Dean & Diagnostic Architect
Certified & Founded by
Dr. Melvin Sewell, M.Sc., Ph.D.
Academic Dean & Diagnostic Architect
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