Clioquinol targets the proteasome and DNA replication enzymes. It forms a stable chelate with copper ions, which inhibits the chymotrypsin-like activity of the proteasome. This leads to the accumulation of ubiquitinated proteins in tumor cells, followed by apoptosis and the inhibition of tumor angiogenesis. It also inhibits certain enzymes related to DNA replication.

U251 and MV-4-11 cells are resistant to the anticancer effects of ciprofloxacin (0.01-1000 uM; 72 hours).
In vitro, Clioquinol has antibacterial and antifungal properties. It inhibits the chymotrypsin-like activity of the proteasome. It has been shown to have antitumor activity in cell culture. It is a chelator of copper and other metal ions.

In vivo, Clioquinol is an orally bioavailable drug. It is used to treat skin infections. It has been studied for its potential applications in neurodegenerative diseases due to its ability to chelate metal ions like zinc and copper, which play a role in conditions such as Alzheimer’s disease. It is neurotoxic in large doses.

Clioquinol is evaluated in cell-free proteasome activity assays. The compound is incubated with purified proteasome and a fluorogenic substrate, and the inhibition of chymotrypsin-like activity is measured. Its metal chelating properties are assessed using spectroscopic methods.

Cell Line: The MV-4-11, and U-251 cell lines
Concentration: 0.01, 0.1, 1, 10, 100, 1000 uM
Incubation Time: 72 hours
Result: In U251 and MV-4-11 cells, the IC50s were 32 and 46 μM, respectively.
Clioquinol is assessed in cell-based assays using tumor cell lines. Cells are treated with Clioquinol, and cell proliferation, apoptosis, and proteasome activity are measured. Its effects on ubiquitinated protein accumulation are evaluated using Western blot analysis.

Clioquinol is administered orally or topically in animal models and in clinical settings. It has been studied in models of Alzheimer's disease and other neurodegenerative diseases. Efficacy is assessed by measuring cognitive function, neuroinflammation, and metal ion levels.

Absorption, Distribution and Excretion
Local absorption is rapid and widespread, especially when the skin is covered with an occlusive dressing or when the drug is applied to large or eroded areas of skin. The amount of crizoquinol absorbed through the skin is sufficient to affect thyroid function tests. Crioquinol is absorbed systemically after topical application to the skin. In two studies, crizoquinol, in combination with corticosteroids, was applied topically as a cream or ointment, and it was estimated that approximately 2-3% of the dose was absorbed systemically. However, in another study, the drug was applied alone to the skin as a 3% cream and covered with an occlusive dressing for 12 hours, and it was estimated that approximately 40% of the dose was absorbed transdermally during this period. Patients with extensive dermatitis apply 15-20 g of 3% clopidogrel ointment twice daily to 40% of the body surface area. Serum concentrations rise to 0.8-1.2 μg/mL within 4 hours of application. In one patient, 15-20 mg of the drug is excreted daily primarily as conjugated metabolites in the urine. This skin treatment results in slightly lower urinary excretion than the daily oral administration of 25 mg (one tablet) cloioquinol. Therefore, 3-4% of the applied cloioquinol is absorbed. 25% is excreted in the urine. Metabolites/Metabolites: Known metabolites of cloioquinol in the human body include cloioquinol O-glucuronide. Biological Half-Life: 11-14 hours.
Clioquinol has a molecular weight of 305.50 and a molecular formula of C9H5ClINO. It has a CAS number of 130-26-7. The compound is a solid. It is soluble in DMSO and should be stored under recommended conditions.

Clioquinol is neurotoxic in large doses, which is why its licence for oral treatment has been withdrawn. It is generally well-tolerated when used topically. The compound is a therapeutic agent and is available by prescription or over-the-counter.

[1].Clioquinol down-regulates mutant huntingtin expression in nvitro and mitigates pathology in a Huntington's disease mouse model.nProc Natl Acad Sci U S A. 2005 Aug 16;102(33):11840-5.

[2]Clioquinol induces pro-death autophagy in leukemia and nmyeloma cells by disrupting the mTOR signaling pathway. Sci Rep. 2014nJul 18;4:5749.

[3]>Clioquinol increases the expression of VGF, a neuropeptide nprecursor, through induction of c-Fos expression. J Pharmacol Sci.n2014;124(4):427-32.

[4]Clioquinol promotes the degradation of metal-dependent namyloid-u03b2 (Au03b2) oligomers to restore endocytosis and ameliorate A03b2ntoxicity. Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):4013-8

Iodochlorohydroxyquinoline is a milky white to brownish-yellow powder, almost odorless, decomposes at 178-179℃, and is used as a topical anti-infective agent. 5-Chloro-7-Iodochlorohydroxyquinoline-8-ol is a monohydroxyquinoline, a compound in which the hydrogen atoms at the 5 and 7 positions of quinoline-8-ol are replaced by chlorine and iodine, respectively. It has antibacterial and antifungal properties and is used in creams for treating skin infections. It has also been investigated as a copper and zinc ion chelating agent for the treatment of Alzheimer's disease. It has multiple functions, including antifungal, antitumor, antibacterial, chelating agent, antiprotozoal drug, and copper chelating agent. It is an organochlorine compound, an organoiodine compound, and a monohydroxyquinoline. Due to neurotoxicity, chloroquinoline was withdrawn from the market in 1983. Chloroquinoline is a standardized chemical allergen. The physiological effects of chloroquinoline are achieved through increased histamine release and cell-mediated immune responses.
CloIodochlorohydroxyquinoline is a highly bioavailable, lipophilic, copper-binding halogenated 8-hydroxyquinoline with antifungal, antiparasitic, and potential antitumor activities. CloIodochlorohydroxyquinoline forms a stable chelate with copper (copper(II) ions), inhibiting chymotrypsin-like activity of the proteasome; therefore, ubiquitinated proteins may accumulate in tumor cells, leading to inhibition of tumor cell apoptosis and tumor angiogenesis. Furthermore, the cloIodochlorohydroxyquinoline-copper complex appears to reduce androgen receptor (AR) expression in human copper-rich prostate cancer cells. Serum copper levels are typically elevated in cancer patients; copper chelation may inhibit copper-dependent endothelial cell proliferation and tumor-secreting angiogenic factors.
A potentially neurotoxic 8-hydroxyquinoline derivative, it has long been used as a topical anti-infective, intestinal anti-amoebic, and vaginal trichomoniasis agent. Oral formulations have been shown to cause subacute myelooptic neuropathy and are banned worldwide.
See also: Iodochlorohydroxyquinoline (note moved to).
Drug Indications
Used as a topical antifungal treatment.

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Mechanism of Action
Clioquinoline has antibacterial activity, but its exact mechanism of action is unclear.Therapeutic Uses
Amoeboid agent; Topical anti-infective agent
Clioquinoline is used topically to treat tinea pedis, tinea cruris, and other skin infections caused by dermatophytes (ringworms).
Veterinary drug: Formerly used as an intestinal anti-infective.
Topical anti-infective agent; Anti-amoebic agent
For more complete data on the therapeutic uses of crizoquinol (7 types), please visit the HSDB record page.Drug Warnings
Although crizoquinol has been previously used to treat diaper rash (diaper dermatitis), its use in children is currently not recommended, and it is contraindicated in children under 2 years of age.
Clioquinol is generally well tolerated after topical application. Occasionally, there have been reports of local irritation, rash, and allergic reactions. If any such reaction occurs, discontinue use and consult a doctor.
Cross-sensitivity reactions may occur with other hydroxyquinolines and quinoline derivatives (such as some antimalarial drugs) and occasionally with iodides. Clioquinol can stain the skin, and there are occasional reports of hair and nail discoloration. Prolonged use of this drug may lead to overgrowth of non-susceptible bacteria, which may require appropriate treatment. When cloioquinol is used topically with a fixed-dose combination of hydrocortisone, the usual precautions for topical corticosteroid treatment should be followed. Because oral cloioquinol treatment (usually with long-term high doses) is associated with ocular/neurotoxic effects (e.g., optic neuritis, optic atrophy, subacute myelooptic neuropathy), and because effective alternatives to topical antifungal agents are available, cloioquinol is not recommended for use in children, and is contraindicated in children under 2 years of age. Transdermal cloioquinol contains iodine, which may interfere with certain thyroid function tests (e.g., protein-bound iodine); therefore, the manufacturer recommends discontinuing topical treatment with this drug and waiting at least one month before performing these tests. The presence of cloioquinol in urine or diapers may cause false-positive results in the ferric chloride test for phenylketonuria. For more complete data on clopidogrel (8 of 8), please visit the HSDB records page.

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Pharmacodynamics
Clopidogrel is a broad-spectrum antibacterial agent with antifungal properties. Applying clopidogrel to large areas or broken skin may result in elevated protein-bound iodine (PBI) levels within one week. Additionally, elevated PBI levels may also occur when treating relatively small areas of skin with clopidogrel for more than one week.
Clioquinol is also known as iodochlorohydroxyquin. It is an antifungal, antibiotic, and antiprotozoal agent. The compound is a therapeutic agent.

C9H5NOCLI

305.4991

304.91

C, 35.38; H, 1.65; Cl, 11.60; I, 41.54; N, 4.58; O, 5.24

130-26-7

130-26-7;16524-58-6 (sulfate);

2788

Light yellow to brown solid powder

2.0±0.1 g/cm3

350.4±37.0 °C at 760 mmHg

175-183 °C

165.7±26.5 °C

0.0±0.8 mmHg at 25°C

1.768

3.86

1

2

0

13

193

0

ClC1=C(C=CC=N2)C2=C(O)C(I)=C1

QCDFBFJGMNKBDO-UHFFFAOYSA-N

InChI=1S/C9H5ClINO/c10-6-4-7(11)9(13)8-5(6)2-1-3-12-8/h1-4,13H

5-chloro-7-iodoquinolin-8-ol

EnteroVioform, Clioquinol, Chinoform, Vioform, Iodochlorhydroxyquin, Entero Septol

2934.99.03.00

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : 50~61 mg/mL (163.67~199.67 mM)

Solubility in Formulation 1: 2.08 mg/mL (6.81 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with heating and sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (6.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 3: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: 2.08 mg/mL (6.81 mM)

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 (Please use freshly prepared in vivo formulations for optimal results.)