Description: <p><b>Fenbendazole</b> (FBZ) — a benzimidazole anthelmintic used in veterinary medicine. Mechanistically a <b>β-tubulin–binding microtubule destabilizer</b> with secondary metabolic and redox effects reported in preclinical oncology models.</p>
<p><b>Primary mechanisms (conceptual rank):</b><br>
1) β-tubulin binding → microtubule depolymerization<br>
2) Mitotic arrest → apoptosis (caspase activation)<br>
3) Glucose uptake / glycolysis interference (reported GLUT inhibition)<br>
4) Redox stress modulation (ROS shifts)<br>
5) p53 pathway interactions (model-dependent)</p>
<p><b>Bioavailability / PK relevance:</b> Poor aqueous solubility; variable oral absorption; extensively metabolized (e.g., to oxfendazole). Human PK data limited; not approved for human oncology use.</p>
<p><b>In-vitro vs oral exposure:</b> Many anti-cancer studies use micromolar concentrations; achievable systemic exposure in humans is uncertain and likely lower without optimized formulations.</p>
<p><b>Clinical evidence status:</b> Preclinical oncology; anecdotal reports only; no controlled oncology RCT evidence.</p>
<br>
-Fenbendazole works by binding to tubulin, a protein that is important in cell division, which may theoretically affect rapidly dividing cells like cancer cells. However, this mechanism is not selective for cancer cells and could affect normal cells as well.<br>
<br>
-Albendazole and fenbendazole, two approved and commonly used benzimidazole anthelmintics<br>
<br>
-Panacure C :1g granules (or 222mg Fenbendazole, for small dogs)<br>
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<h3>Fenbendazole — Cancer vs Normal Cell Pathway Map</h3>
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer Cells</th>
<th>Normal Cells</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>
<tr>
<td>1</td>
<td>β-Tubulin / Microtubule dynamics</td>
<td>↓ (primary)</td>
<td>↓ (proliferating cells)</td>
<td>P/R</td>
<td>Mitotic spindle disruption</td>
<td>Core mechanism; similar class effect to other benzimidazoles. Selectivity depends on proliferation rate.</td>
</tr>
<tr>
<td>2</td>
<td>Mitotic arrest → intrinsic apoptosis</td>
<td>↑</td>
<td>↑ (high proliferation)</td>
<td>R/G</td>
<td>Caspase-mediated cell death</td>
<td>Follows spindle disruption; cancer cells often more susceptible due to mitotic stress vulnerability.</td>
</tr>
<tr>
<td>3</td>
<td>Glucose uptake / Glycolysis (Warburg linkage)</td>
<td>↓ (model-dependent)</td>
<td>↔</td>
<td>R/G</td>
<td>Metabolic stress</td>
<td>Reported GLUT inhibition and reduced hexokinase activity in some models; secondary mechanism.</td>
</tr>
<tr>
<td>4</td>
<td>ROS</td>
<td>↑ (dose-dependent)</td>
<td>↔ / ↑ (high concentration)</td>
<td>P/R</td>
<td>Oxidative stress amplification</td>
<td>Often secondary to metabolic and microtubule stress; may enhance apoptosis.</td>
</tr>
<tr>
<td>5</td>
<td>NRF2 axis</td>
<td>↔ / ↓ (context-dependent)</td>
<td>↔</td>
<td>R/G</td>
<td>Redox-response modulation</td>
<td>Not a primary target; redox shifts may indirectly influence NRF2 signaling.</td>
</tr>
<tr>
<td>6</td>
<td>p53 pathway</td>
<td>↑ (model-dependent)</td>
<td>↔</td>
<td>G</td>
<td>Tumor suppressor activation</td>
<td>Reported stabilization or activation in some cancer lines; dependent on functional p53 status.</td>
</tr>
<tr>
<td>7</td>
<td>PI3K/AKT/mTOR</td>
<td>↓ (secondary; model-dependent)</td>
<td>↔</td>
<td>R/G</td>
<td>Reduced survival signaling</td>
<td>Often downstream of metabolic stress or ROS elevation.</td>
</tr>
<tr>
<td>8</td>
<td>HIF-1α</td>
<td>↓ (model-dependent)</td>
<td>↔</td>
<td>G</td>
<td>Reduced hypoxia adaptation</td>
<td>Linked to metabolic interference; not universally established.</td>
</tr>
<tr>
<td>9</td>
<td>Ca²⁺ signaling</td>
<td>↔ (stress-related)</td>
<td>↔</td>
<td>P/R</td>
<td>Not a primary axis</td>
<td>No consistent evidence of direct Ca²⁺ modulation.</td>
</tr>
<tr>
<td>10</td>
<td>Ferroptosis</td>
<td>↔ (investigational)</td>
<td>↔</td>
<td>R/G</td>
<td>Not established primary mechanism</td>
<td>ROS generation may overlap with lipid peroxidation pathways but not core evidence.</td>
</tr>
<tr>
<td>11</td>
<td>Clinical Translation Constraint</td>
<td>↓ (constraint)</td>
<td>↓ (constraint)</td>
<td>—</td>
<td>PK variability + lack of human oncology data</td>
<td>Veterinary drug; limited human PK; no oncology approval; safety at anti-cancer doses unknown.</td>
</tr>
</table>
<p><b>TSF legend:</b><br>
P: 0–30 min (microtubule binding)<br>
R: 30 min–3 hr (mitotic stress + signaling shifts)<br>
G: >3 hr (apoptosis and phenotype outcomes)</p>