Ivermectin / PFK1 Cancer Research Results

IVM, Ivermectin: Click to Expand ⟱
Features:
Ivermectin , Medicationthat treats some parasitic diseases

Ivermectin (IVM; brands include Stromectol; Rx antiparasitic) — a macrocyclic lactone anthelmintic used for certain parasitic infections. Oncology relevance is primarily repurposing research (preclinical + early trials), not an approved anticancer indication.

Primary mechanisms (conceptual rank):
1) Parasite MoA: glutamate-gated Cl⁻ channel modulation → paralysis/death (invertebrate-selective)
2) Repurposing (cancer): multi-pathway inhibition (Wnt/β-catenin ↓; STAT3 ↓; PI3K/AKT/mTOR ↓; PAK1-linked signaling ↓; model-dependent)
3) Tumor cell stress programs (autophagy/apoptosis ↑; context-dependent)
4) Tumor microenvironment/immune modulation (context-dependent; exploratory)

Bioavailability / PK relevance: Oral; half-life ~18 h; primarily CYP3A4 metabolism; excretion mainly fecal. High-fat meal can increase bioavailability (~2.5× reported in product monograph). CNS exposure is normally limited by P-glycoprotein at the BBB (risk increases if P-gp function is impaired or inhibited).

In-vitro vs oral exposure: Many reported anticancer effects use concentrations that may exceed typical systemic exposure from standard antiparasitic dosing (high concentration only for direct tumor cytotoxicity in many models).

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

Ivermectin — Cancer vs Normal Cell Pathway Map

RankPathway / AxisCancer CellsNormal CellsTSFPrimary EffectNotes / Interpretation
1Wnt/β-catenin ↓ (model-dependent)↔R/G Reduced proliferation / stemness programs Frequently cited repurposing axis; relevance highest in Wnt-dependent contexts.
2STAT3 ↓ (model-dependent)↔R/G Anti-survival transcription blockade Often presented as a central anti-tumor signaling node in repurposing literature.
3PI3K/AKT/mTOR ↓ (model-dependent)↔R/G Reduced anabolic survival signaling Commonly co-reported with Wnt/STAT3 effects; may contribute to cytostatic phenotypes.
4PAK1-linked signaling ↓ (model-dependent)↔R/G Reduced migration / growth signaling Repurposing reviews highlight PAK1 as a putative node; tumor-type dependence is high.
5Autophagy ↑ or ↔ (context-dependent)↔ / ↑ (stress-dependent)R/G Stress adaptation vs growth suppression Often cytostatic; can support survival or contribute to death depending on context.
6 Glycolysis / Warburg (glucose uptake, lactate output) ↓ (model-dependent; secondary to energy stress; high concentration only) ↔ / ↓ (high concentration only) R/G Reduced glycolytic flux / lactate production Often downstream of mitochondrial ATP stress and PI3K/AKT/mTOR inhibition; not a uniformly demonstrated primary ivermectin target and typically requires higher experimental exposure.
7Apoptosis (intrinsic; caspases) ↑ (model-dependent; high concentration only)↔ / ↑ (high exposure)R/G Programmed cell death Typically downstream of pathway inhibition/stress; exposure gap common.
8ROS ↑ or ↔ (context-dependent)↔P/R Secondary stress contributor Not a canonical primary target; can emerge downstream of stress signaling.
9NRF2 (protective vs resistance role) ↔ / ↑ (adaptive; context-dependent)↔ / ↑ (adaptive)R/G Stress-response adjustment Secondary; could blunt efficacy if antioxidant adaptation dominates.
10HIF-1α ↔ / ↓ (model-dependent)↔G Not a consistent primary axis Reported variably; treat as secondary unless tumor model is hypoxia-driven.
11Ferroptosis ↔ (insufficiently established)↔R/G Not canonical Not a standard ivermectin-first claim; include only with specific supporting studies.
12Ca²⁺ signaling ↔↔P/R No primary role Include only if a model explicitly measures Ca²⁺/ER-stress endpoints.
13Clinical Translation Constraint ↓ (constraint)↓ (constraint)— Exposure + evidence + BBB safety context Most tumor-directed effects are preclinical and often high-concentration. PK/food effects (high-fat meal ↑ exposure), CYP3A4 metabolism, and P-gp BBB protection (neurotoxicity risk if impaired/inhibited) are key constraints; oncology trials remain early.

TSF legend:
P: 0–30 min (primary/rapid effects)
R: 30 min–3 hr (acute signaling/stress response)
G: >3 hr (gene-regulatory/phenotype outcomes)
PFK1, Phosphofructokinase-1: Click to Expand ⟱
Source:
Type:
Phosphofructokinase-1 (PFK1) is a key regulatory enzyme in glycolysis that catalyzes the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate.
– As a rate-limiting enzyme in glycolysis, PFK1 is subject to complex regulation through allosteric effectors including ATP, AMP, and fructose-2,6-bisphosphate.
• Metabolic Control:
–PFK1 activity is central to controlling the pace of glycolysis, thereby influencing energy production and intermediary metabolite supply.
– In highly proliferative cells or cells under growth conditions, increased glycolytic flux (and, by extension, PFK1 activity) supports the biosynthetic demands of cell division.

– Many tumors (including breast, colorectal, and lung cancers) have been reported to have increased PFK1 expression/activity relative to normal tissues.
– High glycolytic flux, driven partly by enhanced PFK1, supports rapid cell proliferation and survival in the nutrient/stress-challenged tumor microenvironment.

Inhibitors:(typically glycolysis is targeted more broadly)
-Citrate
-Hydrogen ions (pH) – Acidic conditions can have inhibitory effects.
-3PO: inhibits PFKFB3, thereby indirectly reducing PFK1 activity.
-Resveratrol can downregulate glycolytic flux in cancer cells, which may indirectly affect PFK1 activity.
- FMDs offer an indirect strategy to modulate cancer metabolism by broadly reducing glycolysis. Their impact on PFK1 is likely part of a complex network of metabolic adaptations rather than a direct inhibitory effect.
Scientific Papers found: Click to Expand⟱
1070- IVM,    Ivermectin accelerates autophagic death of glioma cells by inhibiting glycolysis through blocking GLUT4 mediated JAK/STAT signaling pathway activation
- vitro+vivo, GBM, NA
TumCG↓, LC3II↑, p62↓, ATP↓, Pyruv↓, GlucoseCon↑, HK2↓, PFK1↓, GLUT4↓, Glycolysis↓, JAK2↓, p‑STAT3↓, p‑STAT5↓,

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 ⓘ

ATP↓, 1,  

Core Metabolism/Glycolysis ⓘ

GlucoseCon↑, 1,   Glycolysis↓, 1,   HK2↓, 1,   PFK1↓, 1,   Pyruv↓, 1,  

Autophagy & Lysosomes ⓘ

LC3II↑, 1,   p62↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

p‑STAT3↓, 1,   p‑STAT5↓, 1,   TumCG↓, 1,  

Barriers & Transport ⓘ

GLUT4↓, 1,  

Immune & Inflammatory Signaling ⓘ

JAK2↓, 1,  
Total Targets: 13

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: PFK1, Phosphofructokinase-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#:10  Target#:988  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

Home Page