Niclosamide for Cancer and other Diseases - 2025 Review Paper from China
Niclosamide was approved by FDA in 1982 for treating tapeworm infections, and was designated an essential drug by WHO.
Niclosamide for Cancer Mechanisms:
1. Mitochondrial uncoupling - this is its major anti-cancer mechanism
Niclosamide acts like a mild “leak” in the mitochondrial membrane, letting protons slip across without making ATP. This increases oxygen use, lowers ATP levels, raises AMP/ATP ratio & activates AMPK (energy sensor) to inhibit mTOR (slows down cancer cell growth).
Cancer cells, which often rely on inefficient energy pathways (Warburg effect), are especially vulnerable.
This can lead to inhibition of ATP synthesis, exhausting cellular energy reserves, metabolic stress, and cell death.
2. Signal pathway modulation - It inhibits several “pro-cancer” pathways, including:
- Wnt/β-catenin (important in cancer proliferation, especially colorectal).
- mTOR (controls cell proliferation, growth and metabolism).
- Notch pathway (controls proliferation, growth, angiogenesis and cellular migration)
- STAT3, NF-κB, etc. (cancer survival, proliferation).
- Promotes apoptosis (programmed cell death) and reduce inflammation.
3. Combination with existing chemotherapies
4. Addresses Multi-Drug Resistance - by enhancing production of reactive oxygen species.
OTHER DISEASES - beyond cancer, Niclosamide’s versatility includes:
Anti-bacterial - strong in vitro activity against resistant gram-positive bacteria.
its antibacterial activity involves altering bacterial morphology, reducing intracellular ATP, and inhibiting α-HL secretion (Staph Aureus)
it inhibits all three toxins of Clostridium difficile by targeting a host process essential for toxin entry into colonocytes. In a mouse model, it reduced both primary disease and recurrence without affecting gut microbiota diversity
it demonstrates marked inhibition of vancomycin-resistant Enterococcus faecium (VRE)
It effectively eliminates H. pylori adhesion/invasion
Anti-Fungal - demonstrates impressive antifungal effects in vitro and in vivo niclosamide effectively disrupted and removed biofilms of drug-resistant Candida albicans and Candida auris by targeting mitochondrial respiration
Anti-Viral - Niclosamide could have action against SARS-CoV, MERS, Zika, Hepatitis C, Ebola, EBV
Niclosamide inhibits viral replication by reducing mTOR activation and prevents viral entry
inhibits virion production in EBV-infected cells while showing cytotoxicity and inducing cell cycle arrest
demonstrates strong activity against RSV in vitro, with a 94 % inhibition rate
suppresses Hepatitis C replication and reduces viral load
Metabolic disorders (e.g., Type II Diabetes, fatty liver): Mitochondrial effects and AMPK activation can improve energy balance and reduce fat accumulation.
Diabetes: modulates metabolic pathways, improves insulin sensitivity
Fatty liver (NASH, NAFLD) - reduces hepatic inflammation
Neuropathic Pain - reduces inflammation by inhibiting NF-kB, STAT3
alleviates pain and nerve damage
Rheumatoid Arthritis - inhibits NF-kB activation
reduces secretion of IL-6 and other inflammatory cytokines, blocks migration and invasion of RA fibroblast-like synoviocytes.
Psoriasis - inhibits keratinocyte hyperproliferation and reduces inflammation by downregulation of STAT3, NF-kB.
Airway Diseases (Asthma, Cystic Fibrosis, COPD)
- Niclosamide inhibits certain Ca-activated Cl channels involved in mucus hypersecretion & bronchoconstriction (reduces mucus production & secretion.
- it blocks release of mucus and inflammatory mediators which reduces bronchoconstriction.
- it blocks release of mucus and inflammatory mediators which reduces bronchoconstriction.
- anti-fibrotic agent for lung fibrosis - Niclosamide downregulates expression of collagen proteins and inhibits pro-fibrotic cytokines.
- inhibits STAT3, AKT, and Wnt/β-catenin pathways
- reduced immune cell activation
- reversal of skin and lung fibrosis and reduced rate of inflammation
CONCLUSION:
Ivermectin, Mebendazole and Fenbendazole are leading the repurposed drug revolution but Niclosamide is the most promising of the other anti-parasitics!
References:
- Laila UE et al. Pharmacological advances and therapeutic applications of niclosamide in cancer and other diseases. European Journal of Medicinal Chemistry 2025.
- Makis W. X.com (May 2026)
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some of those are OTC. how do I get niclosamide without traveling to a WHO med subsidized country?
ReplyDeleteRather than taking niclosamide orally, consider the use of finely powdered NIC,
ReplyDeletecompounded - at home, using cocoa butter and a suppository mold kit from Amazon - into a lipid base rectal suppository. As has
been cited in several studies and texts, this drug is minimally
absorbed by the human gastrointestinal tract for systemic
circulation. As a result, the U.S. FDA and the WHO have,
for six decades, assessed oral niclosamide as safe,
producing no significant or serious side effects.
When applied to cell cultures, however, niclosamide is
notable in achieving mitochondrial membrane depolarization,
Signal Transducer and Activator of Transcription 3
(STAT3) signaling pathway inhibition, disruption of the
mTOR pathway, degradation of LRP6 to inhibit the
Wnt/β-catenin pathway; suppression of the NF-κB pathway
by inhibiting IκB kinase (IKK), and - as you report -
HIF-1α inhibition.
For the above characteristics, niclosamide has been profiled by
some researchers as a possible “magic bullet”. Unfortunately,
its insolubility and resultant poor bioavailability is generally
highlighted as a prime obstacle. However, just as significant is
its extreme degradation on passing through the gut, with its
exposure to enzymes CYP1A2 and UGT1A1. (The activity levels
of these enzymes in standard lab rodents, however, are
significantly higher.) As a result, oral administration produces
little systemic uptake. Could these metabolic changes be
evaded by utilizing an alternative but well established route
used with similarly insoluble medications - rectal suppository ?
Insoluble niclosamide is fortunately highly lipophilic LogP of 3.91),
as well as weakly acid - an estimated pKa of 5.6-6.89 - with a
molecular weight of 327.12g/mol. These are all physical character-
-istics common to other oral medications which, when delivered
via rectal suppository, produce therapeutic blood levels. The
distal rectum’s inferior and middle veins are remarkably efficient
at transporting insoluble drugs into systemic circulation.
Unfortunately, the superior rectal vein (and anastomoses between
the inferior, middle and superior veins) may problematically route
some of the medication into the portal vein and the liver. This might
be mitigated by maintaining a vertical body position post-administration
for 30 minutes or so in an upright seated position, effectively keeping
the bulk of the dose distally.
From my review of the studies on niclosamide, this route has never
been attempted. My query last year to the Bayer Company regarding
this route drew a June 14, 2024 reply: “Thank you for your inquiry.
We have no information of any healthcare practitioners or clinical trials
using niclosamide compounded as suppositories.”
Perhaps rectal administration would merit, if not a formal trial,
some “self-experimentation”, an approach with a notable
history in the annals of medicine and 8 Nobel Prize winners
(cf. Drs. Jonas Salk, Barry Marshall, Werner Forssmann.)
Unfortunately, generating any significant profits from a
generic drug delivered rectally is unlikely.
(First, niclosamide has been available from MS Traders in India, distributing “Niclosig” 500 mg tablets, made by HaB Pharmaceuticals & Research Ltd. )
ReplyDeleteConsider - rather than oral delivery of NIC- the use of finely powdered niclosamide,
compounded into a lipid base rectal suppository. As has
been cited in several studies and texts, this drug is minimally
absorbed by the human gastrointestinal tract for systemic
circulation. As a result, the U.S. FDA and the WHO have,
for six decades, assessed oral niclosamide as safe,
producing no significant or serious side effects.
When applied to cell cultures, however, niclosamide is
notable in achieving mitochondrial membrane depolarization,
Signal Transducer and Activator of Transcription 3
(STAT3) signaling pathway inhibition, disruption of the
mTOR pathway, degradation of LRP6 to inhibit the
Wnt/β-catenin pathway; suppression of the NF-κB pathway
by inhibiting IκB kinase (IKK), and - as you report -
HIF-1α inhibition.
For the above characteristics, niclosamide has been profiled by
some researchers as a possible “magic bullet”. Unfortunately,
its insolubility and resultant poor bioavailability is generally
highlighted as a prime obstacle. However, just as significant is
its extreme degradation on passing through the gut, with its
exposure to enzymes CYP1A2 and UGT1A1. (The activity levels
of these enzymes in standard lab rodents, however, are
significantly higher.) As a result, oral administration produces
little systemic uptake. Could these metabolic changes be
evaded by utilizing an alternative but well established route
used with similarly insoluble medications - rectal suppository ?
Insoluble niclosamide is fortunately highly lipophilic LogP of 3.91),
as well as weakly acid - an estimated pKa of 5.6-6.89 - with a
molecular weight of 327.12g/mol. These are all physical character-
-istics common to other oral medications which, when delivered
via rectal suppository, produce therapeutic blood levels. The
distal rectum’s inferior and middle veins are remarkably efficient
at transporting insoluble drugs into systemic circulation.
Unfortunately, the superior rectal vein (and anastomoses between
the inferior, middle and superior veins) may problematically route
some of the medication into the portal vein and the liver. This might
be mitigated by maintaining a vertical body position post-administration
for 30 minutes or so in an upright seated position, effectively keeping
the bulk of the dose distally.
From my review of the studies on niclosamide, this route has never
been attempted. My query last year to the Bayer Company regarding
this route drew a June 14, 2024 reply: “Thank you for your inquiry.
We have no information of any healthcare practitioners or clinical trials
using niclosamide compounded as suppositories.”
Perhaps rectal administration would merit, if not a formal trial,
some “self-experimentation”, an approach with a notable
history in the annals of medicine and 8 Nobel Prize winners
(cf. Drs. Jonas Salk, Barry Marshall, Werner Forssmann.)
Unfortunately, generating any significant profits from a
generic drug delivered rectally is unlikely