Cantharidin
Identification
- Brand Names
- Cantharone Plus
- Generic Name
- Cantharidin
- DrugBank Accession Number
- DB12328
- Background
Cantharidin is a naturally occurring odorless, colorless fatty substance of the terpenoid class that is produced as an oral fluid in the alimentary canal of the male blister beetle 1,2. For its natural purpose, the male blister beetle secretes and presents the cantharidin to a female beetle as a copulatory gift during mating. Post-copulation, the female beetle places the cantharidin over her eggs as protection against any potential predators.
Available synthetically since the 1950s, topical applications of cantharidin have been used predominantly as a treatment for cutaneous warts since that time 1,2. In 1962 however, marketers of cantharidin failed to produce sufficient efficacy data, resulting in the FDA revision of approval of cantharidin 2.
Today, topical cantharidin products do not necessarily demonstrate any particular better effectiveness at treating topical skin conditions like warts than other commonly available vesicant and/or keratolytics although various studies have also investigated the possibility of using cantharidin as an inflammatory model or in cancer treatment 2. Regardless, the onging lack of FDA approval is likely related to certain toxic effects that were observed following oral ingestion, which includes ulceration of the gastrointestinal and genitourinary tracts, along with electrolyte and renal function disturbance in humans and animals 1.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Cantharidin (DB12328)
- Weight
- Average: 196.202
Monoisotopic: 196.073558866 - Chemical Formula
- C10H12O4
- Synonyms
- 1,2-Dimethyl-3,6-epoxyperhydrophthalic anhydride
- Cantharidin
- Cantharidine
- Cantharone
- exo-1,2-cis-Dimethyl-3,6-epoxyhexahydrophthalic anhydride
- Kantharidin
Pharmacology
- Indication
The only therapeutic use for which cantharidin is currently primarily indicated for is as an active ingredient in topical agents for treating common warts (verruca vulgaris), periungual warts, plantar warts, and molluscum contagiosum 1,2,8.
At the same time, such topical cantharidin applications have also been used for a number of off-label indications like callus removal, cutaneous leishmaniasis, herpes zoster, and acquired perforating dermatosis 2. Furthermore, since most topical cantharidin applications are most commonly available in a 0.7% formulation or a more potent 1% mixture, the 0.7% formulation is most commonly indicated for the treatment of common warts, periungual warts, and molluscum contagiosum while the more potent 1% mixture is typically limited only for use by healthcare professionals in a clinical setting for treating plantar warts and other more specialized off-label conditions 1,2,8.
Moreover, there have also been studies into whether or not cantharidin could be effective at being used as an inflammatory model or in cancer treatment - either of which has yet to formally elucidate any results 2.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Cantharidin is a natural toxin produced by the blistering beetle that possesses both vesicant (blistering) and keratolytic effects 1,2. The substance elicits these effects by inducing acantholysis (loss of intercellular connections) through the targeting of the desmosomal dense plaque, resulting in the detachment of the desmosomes from the tonofilaments 1,2. Cantharidin's effectiveness against warts is proposed to be a result of the exfoliation of the wart body as a consequence of the compound's acantholytic action 8. This acantholytic action generally does not go beyond the epidermal cells so that the basal layer remains intact and minimal effect occurs on the corium 8. There is consequently no scarring from the topical application of cantharidin 8.
- Mechanism of action
Cantharidin is specifically absorbed by lipids in the membrane of epidermal keratinocytes, where it activates the release of neutral serine proteases 1,2. These enzymes subsequently break the peptide bonds in surrounding proteins, leading to the progressive degeneration of desmosomal dense plaques, which are important cellular structures that participate in cell-to-cell adhesion 1,2. Such degeneration results in the detachment of the tonofilaments that hold cells together. This process as a whole leads to the selective acantholysis (loss of cellular connections) and blistering of the skin when the cantharidin topical application is applied upon specific topical developments like warts 1,2. A blister(s) at the application site develop within 24 to 48 hours of application and typically resolve within 4 to 7 days 1,2. Factors that can modify this proposed time frame include the volume or concentration of cantharidin used, physical contact time of the applied compound (usually between 4 to 24 hours), the presence of any occlusive dressings, or even patient sensitivity to cantharidin 1,2. The blistered lesions ultimately heal without scarring 1,2.
Finally, there are some studies that suggest cantharidin's chemical profile as a potent and selective inhibitor of protein phosphatase 2A confers upon it an oxidative stress-independent growth inhibition of pancreatic cancer cells through cancer cell-cycle arrest and apoptosis 3.
Nevertheless, the fact that little data regarding the pharmacodynamics and pharmacokinetics of cantharidin in the human body exists 5 and certain toxic effects of cantharidin that have been observed following oral ingestion in humans like ulceration of the gastrointestinal and genitourinary tracts, along with electrolyte and renal function disturbance 1 are strong reasons as to why the compound currently lacks FDA approval is used fairly limitedly for formal therapeutic indications.
Target Actions Organism UAryl hydrocarbon receptor agonistHumans ASkin epithelial cells vesicantHumans - Absorption
Cantharidin is absorbed from the gastrointestinal tract, and, to a limited extent from the skin as well 6.
Little pharmacodynamic and pharmacokinetic data regarding cantharidin in the human body currently exists; recruitment for First-Time-In-Human clinical trials regarding such information have been ongoing in 2018 5. There are however some studies regarding such data in animal models like beagle dogs 4.
- Volume of distribution
After oral or IP injection of (3)H-labeled cantharidin, high levels of radioactivity distributed to and were exhibited in the bile, kidney, liver, stomach, and tumor cells of ascites hepatoma-bearing mice 6. Such distribution suggests the agent has an affinity for liver and tumor tissues 6.
Little pharmacodynamic and pharmacokinetic data regarding cantharidin in the human body currently exists; recruitment for First-Time-In-Human clinical trials regarding such information have been ongoing in 2018 5. There are however some studies regarding such data in animal models like beagle dogs 4.
- Protein binding
Little pharmacodynamic and pharmacokinetic data regarding cantharidin in the human body currently exists; recruitment for First-Time-In-Human clinical trials regarding such information have been ongoing in 2018 5. There are however some studies regarding such data in animal models like beagle dogs 4.
- Metabolism
Little pharmacodynamic and pharmacokinetic data regarding cantharidin in the human body currently exists; recruitment for First-Time-In-Human clinical trials regarding such information have been ongoing in 2018 5. There are however some studies regarding such data in animal models like beagle dogs 4.
- Route of elimination
It has been observed that absorbed cantharidin is excreted by the kidney 6.
Little pharmacodynamic and pharmacokinetic data regarding cantharidin in the human body currently exists; recruitment for First-Time-In-Human clinical trials regarding such information have been ongoing in 2018 5. There are however some studies regarding such data in animal models like beagle dogs 4.
- Half-life
Little pharmacodynamic and pharmacokinetic data regarding cantharidin in the human body currently exists; recruitment for First-Time-In-Human clinical trials regarding such information have been ongoing in 2018 5. There are however some studies regarding such data in animal models like beagle dogs 4.
- Clearance
Little pharmacodynamic and pharmacokinetic data regarding cantharidin in the human body currently exists; recruitment for First-Time-In-Human clinical trials regarding such information have been ongoing in 2018 5. There are however some studies regarding such data in animal models like beagle dogs 4.
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Side effects observed from the topical application of cantharidin include blistering, erythema, pain, bleeding, ring warts, post-inflammatory hyperpigmentation, lymphangitis, secondary bacterial cellulitis, scarring, and varicelliform vesicular dermatitis 2.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Cantharidin 0.7% Liquid 0.7 g/100g Topical Sincerus Florida, LLC 2019-05-17 Not applicable US 
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image CANTHACUR PS %1,%5,%30 TOPIKAL SOLUSYON 7,5 ML Cantharidin (10.2 mg/ml) + Podophyllin (51 mg/ml) + Salicylic acid (306 mg/ml) Solution Topical ASSOS İLAÇ KİMYA GIDA ÜRÜNLERİ ÜRETİM VE TİC. A.Ş. 2020-08-14 Not applicable Turkey 
Canthacur-PS Cantharidin (1 %) + Podophyllin (5 %) + Salicylic acid (30 %) Liquid Topical Paladin Labs Inc 1983-12-31 2017-05-30 Canada 
Cantharone Plus Cantharidin (1 %) + Podophyllin (2 %) + Salicylic acid (30 %) Liquid Topical Dormer Laboratories Inc. 1984-12-31 Not applicable Canada - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Cantharidin 0.7% Cantharidin (0.7 g/100g) Liquid Topical Sincerus Florida, LLC 2019-05-17 Not applicable US Cantharidin 1% / Podophyllum Resin 5% / Salicylic Acid 30% Cantharidin (1 g/100g) + Podophyllin (5 g/100g) + Salicylic acid (30 g/100g) Liquid Topical Sincerus Florida, LLC 2019-05-17 Not applicable US
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as furofurans. These are organic compounds containing a two furan rings fused to each other. Furan is a five-membered aromatic ring with four carbon atoms and one oxygen atom.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Furofurans
- Sub Class
- Not Available
- Direct Parent
- Furofurans
- Alternative Parents
- Dicarboxylic acids and derivatives / Tetrahydrofurans / Carboxylic acid anhydrides / Lactones / Oxacyclic compounds / Dialkyl ethers / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- Aliphatic heteropolycyclic compound / Carbonyl group / Carboxylic acid anhydride / Carboxylic acid derivative / Dialkyl ether / Dicarboxylic acid or derivatives / Ether / Furofuran / Hydrocarbon derivative / Lactone
- Molecular Framework
- Aliphatic heteropolycyclic compounds
- External Descriptors
- monoterpenoid, cyclic dicarboxylic anhydride (CHEBI:64213)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- IGL471WQ8P
- CAS number
- 56-25-7
- InChI Key
- DHZBEENLJMYSHQ-XCVPVQRUSA-N
- InChI
- InChI=1S/C10H12O4/c1-9-5-3-4-6(13-5)10(9,2)8(12)14-7(9)11/h5-6H,3-4H2,1-2H3/t5-,6+,9+,10-
- IUPAC Name
- (1R,2S,6R,7S)-2,6-dimethyl-4,10-dioxatricyclo[5.2.1.0²,⁶]decane-3,5-dione
- SMILES
- [H][C@]12CC[C@]([H])(O1)[C@]1(C)C(=O)OC(=O)[C@]21C
References
- General References
- Al-Dawsari NA, Masterpol KS: Cantharidin in Dermatology. Skinmed. 2016 Apr 1;14(2):111-4. eCollection 2016. [Article]
- Torbeck R, Pan M, DeMoll E, Levitt J: Cantharidin: a comprehensive review of the clinical literature. Dermatol Online J. 2014 Jun 15;20(6). [Article]
- Li W, Xie L, Chen Z, Zhu Y, Sun Y, Miao Y, Xu Z, Han X: Cantharidin, a potent and selective PP2A inhibitor, induces an oxidative stress-independent growth inhibition of pancreatic cancer cells through G2/M cell-cycle arrest and apoptosis. Cancer Sci. 2010 May;101(5):1226-33. doi: 10.1111/j.1349-7006.2010.01523.x. Epub 2010 Feb 5. [Article]
- Dang Y, Zhu C: [Pharmacokinetics and bioavailability of cantharidin in beagle dogs]. Zhongguo Zhong Yao Za Zhi. 2009 Aug;34(16):2088-91. [Article]
- NIH ClinicalTrials.gov: First-time-in-Human (FTIH) Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single (in Both Fed and Fasted States) or Repeat Doses of GSK3358699 [Link]
- NLM Toxnet: Catharidine [Link]
- TITCK Product Information: Canthacur (cantharidin) topical solution [Link]
- Canthacur (cantharidin 0.7%) Solution for Topical Use Package Insert [File]
- External Links
- KEGG Compound
- C16778
- PubChem Compound
- 5944
- PubChem Substance
- 347828590
- ChemSpider
- 5731
- BindingDB
- 50090505
- 1984
- ChEBI
- 64213
- ChEMBL
- CHEMBL48449
- ZINC
- ZINC000017611186
- Wikipedia
- Cantharidin
- MSDS
- Download (26.4 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Warts, Genital 1 2 Completed Treatment DNA Virus Infections / Papillomavirus Infections / Skin Diseases / Skin Diseases, Infectious / Skin Diseases, Viral / Tumor Virus Infections / Verruca (Warts) / Verruca Vulgaris / Virus Diseases / Warts Hand 1 2 Completed Treatment Molluscum Contagiosum 2 1 Completed Diagnostic Rheumatoid Arthritis 1 1 Completed Other Inflammation 1 0 Completed Basic Science Cardiovascular Function 1 Not Available Completed Treatment Molluscum Contagiosum, Skin Disease 1 Not Available Completed Treatment Verruca Vulgaris 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution Topical Solution Topical Liquid Topical 0.7 g/100g Liquid Topical - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 16.6 mg/mL ALOGPS logP 1.1 ALOGPS logP 1.06 ChemAxon logS -1.1 ALOGPS pKa (Strongest Basic) -4.2 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 3 ChemAxon Hydrogen Donor Count 0 ChemAxon Polar Surface Area 52.6 Å2 ChemAxon Rotatable Bond Count 0 ChemAxon Refractivity 45.4 m3·mol-1 ChemAxon Polarizability 18.54 Å3 ChemAxon Number of Rings 3 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Transcription regulatory region dna binding
- Specific Function
- Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes...
- Gene Name
- AHR
- Uniprot ID
- P35869
- Uniprot Name
- Aryl hydrocarbon receptor
- Molecular Weight
- 96146.705 Da
References
- Zhang S, Qin C, Safe SH: Flavonoids as aryl hydrocarbon receptor agonists/antagonists: effects of structure and cell context. Environ Health Perspect. 2003 Dec;111(16):1877-82. [Article]
References
Drug created on October 20, 2016 21:57 / Updated on February 21, 2021 18:53