Niclosamide (Niclocide) / PD-1 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
PD-1, Programmed Death-1: Click to Expand ⟱
Source:
Type: protein
PD-1 (Programmed Death-1) is a protein that plays a crucial role in the immune system's ability to fight cancer. It is a checkpoint protein that helps regulate the immune response by preventing the immune system from attacking healthy cells.
PD-1 is often exploited by cancer cells to evade the immune system. Cancer cells can produce proteins that bind to PD-1, inhibiting the immune response and allowing the cancer cells to grow and proliferate unchecked.

However, researchers have discovered that blocking the PD-1 pathway can help restore the immune system's ability to fight cancer. This has led to the development of PD-1 inhibitors, a class of cancer therapies that target the PD-1 protein.

PD-1: Upregulated on tumor-infiltrating lymphocytes (TILs), reflecting chronic antigen exposure and an “exhausted” T cell phenotype.
PD-L1 and PD-L2: Frequently overexpressed by many tumor types (e.g., non–small cell lung cancer, melanoma, renal cell carcinoma, head and neck cancers).
Scientific Papers found: Click to Expand⟱
5254- NCL,    The magic bullet: Niclosamide
- Review, Var, NA
Wnt↓, β-catenin/ZEB1↓, RAS↓, STAT3↓, NOTCH↓, E2Fs↓, mTOR↓, eff↑, PD-1↓, PD-L1↓, BioAv↝, toxicity↓, BioAv↑, ETC↑, NADH:NAD↓, TCA↑, Warburg↓, Diff↑, AMPK↑, P53↑, PP2A↑, HIF-1↓, KRAS↓, Myc↓, RadioS↑, ChemoSen↑, Dose↝, Dose↑,

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:


Mitochondria & Bioenergetics ⓘ

ETC↑, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   NADH:NAD↓, 1,   TCA↑, 1,   Warburg↓, 1,  

Cell Death ⓘ

Myc↓, 1,  

DNA Damage & Repair ⓘ

P53↑, 1,  

Cell Cycle & Senescence ⓘ

E2Fs↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

Diff↑, 1,   mTOR↓, 1,   NOTCH↓, 1,   RAS↓, 1,   STAT3↓, 1,   Wnt↓, 1,  

Migration ⓘ

KRAS↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

HIF-1↓, 1,  

Immune & Inflammatory Signaling ⓘ

PD-1↓, 1,   PD-L1↓, 1,  

Protein Aggregation ⓘ

PP2A↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   BioAv↝, 1,   ChemoSen↑, 1,   Dose↑, 1,   Dose↝, 1,   eff↑, 1,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

KRAS↓, 1,   Myc↓, 1,   PD-L1↓, 1,  

Functional Outcomes ⓘ

toxicity↓, 1,  
Total Targets: 31

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: PD-1, Programmed Death-1
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#:709  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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