Niclosamide (Niclocide) / MEK Cancer Research Results

NCL, Niclosamide (Niclocide): Click to Expand ⟱
Features:

Niclosamide (brand: Niclocide; NIC) — salicylanilide anthelmintic (tapeworm drug) being investigated for drug repurposing in oncology due to multi-pathway signaling inhibition and mitochondrial/energy-stress effects. Sources: Rx/essential-medicines antiparasitic; multiple repurposing reviews.

Primary mechanisms (conceptual rank):
1) Mitochondrial energy disruption (uncoupling / ATP depletion; AMPK-linked energy stress)
2) Wnt/β-catenin inhibition (LRP6/β-catenin axis; stemness/CSC phenotypes)
3) STAT3 inhibition (anti-survival transcription)
4) mTORC1 suppression (growth/anabolism ↓; autophagy context)
5) NF-κB / Notch modulation (context-dependent; anti-inflammatory/anti-survival)

Bioavailability / PK relevance: Poor solubility and low/variable oral systemic exposure are major constraints; formulation work (e.g., solution approaches) is used to improve reproducibility/systemic availability.

In-vitro vs oral exposure: Many anticancer effects are observed at concentrations that can exceed typical systemic exposure from standard oral dosing (qualifier: high concentration only for direct tumor cytotoxicity in many models).

Clinical evidence status: Approved antiparasitic; oncology remains preclinical + early/small human repurposing studies (no established oncology RCT approval/indication).

Niclosamide (Niclocide) — Cancer vs Normal Cell Pathway Map

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Mitochondrial energy metabolism (OXPHOS uncoupling / ATP) ↓ ATP (primary; dose-dependent) ↓ ATP (high concentration only) P/R Energy stress → growth inhibition Core pharmacology includes mitochondrial/energy disruption; can trigger downstream stress signaling.
2 Wnt/β-catenin (LRP6/β-catenin; CSC/stemness) ↓ (model-dependent) ↔ R/G Reduced proliferation / stemness programs Frequently highlighted in repurposing; relevant in Wnt-driven or CSC-enriched contexts.
3 STAT3 ↓ ↔ R/G Anti-survival transcription blockade Often positioned as a central anti-tumor axis and combination-sensitization mechanism.
4 mTORC1 / growth-anabolism ↓ ↔ / ↓ (stress-dependent) R/G Reduced anabolic signaling Frequently co-reported with Wnt/STAT3 inhibition; can couple to autophagy responses.
5 AMPK (energy-stress sensor) ↑ (context-dependent) ↑ (stress-dependent) R Catabolic shift / growth suppression Often downstream of ATP depletion; can antagonize mTORC1 signaling.
6 NF-κB ↓ (context-dependent) ↓ (context-dependent) R/G Reduced inflammatory / survival programs Not always dominant; varies by model and inflammatory dependence.
7 Notch ↓ (model-dependent) ↔ G Differentiation / stemness modulation Reported in repurposing literature; often secondary to broader stress/signaling effects.
8 ROS ↑ (dose-dependent) ↔ / ↑ (high concentration only) P/R Oxidative stress contribution Can be downstream of mitochondrial disruption; may contribute to cytotoxicity or resistance depending on context.
9 NRF2 (protective vs resistance role) ↔ / ↑ (adaptive; context-dependent) ↔ / ↑ (adaptive) R/G Stress-response adjustment Typically secondary; may reduce sensitivity if antioxidant adaptation dominates.
10 Autophagy ↑ or ↓ (context-dependent) ↔ / ↑ (stress-dependent) R/G Stress adaptation vs cell-death coupling Often described as a stress-response phenotype; can be cytostatic or pro-death depending on tumor context.
11 Ca²⁺ signaling ↔ (stress-related) ↔ P/R No primary axis Not a canonical primary target; include only if a specific model shows ER/mitochondrial Ca²⁺ disruption.
12 Clinical Translation Constraint ↓ (constraint) ↓ (constraint) — Exposure variability + formulation dependence Poor solubility/low systemic exposure and high variability with oral dosing drive repurposing limitations; solution/formulation approaches aim to increase systemic availability.

TSF legend: P: 0–30 min; R: 30 min–3 hr; G: >3 hr
MEK, Mitogen-Activated Protein Kinase Kinase: Click to Expand ⟱
Source:
Type: protein kinase
MEK (Mitogen-Activated Protein Kinase Kinase) is a protein kinase that plays a crucial role in the regulation of cell growth, differentiation, and survival.
MEK is often overexpressed or mutated, leading to the activation of downstream signaling pathways that promote cell growth, survival, and metastasis. MEK inhibitors have been developed as a therapeutic strategy to target cancer cells and inhibit their growth.
Scientific Papers found: Click to Expand⟱
1271- NCL,    Niclosamide inhibits ovarian carcinoma growth by interrupting cellular bioenergetics
- vitro+vivo, Ovarian, SKOV3
Wnt/(β-catenin)↓, mTOR↓, STAT3↓, NF-kB↓, NOTCH↓, TumCG↓, Apoptosis↑, MEK↓, ERK↓, mitResp↓, Glycolysis↓, ROS↑, JNK↑,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

MEK↓, 1,   mitResp↓, 1,  

Core Metabolism/Glycolysis ⓘ

Glycolysis↓, 1,  

Cell Death ⓘ

Apoptosis↑, 1,   JNK↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   mTOR↓, 1,   NOTCH↓, 1,   STAT3↓, 1,   TumCG↓, 1,   Wnt/(β-catenin)↓, 1,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,  
Total Targets: 13

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: MEK, Mitogen-Activated Protein Kinase Kinase
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:13  Target#:860  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

Home Page