| Candidate ID: | R1442 |
| Source ID: | DB12328 |
| Source Type: | approved; investigational |
| Compound Type: |
small molecule
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| Compound Name: |
Cantharidin
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| Synonyms: |
1,2-Dimethyl-3,6-epoxyperhydrophthalic anhydride; Cantharidin; Cantharidine; Cantharone; exo-1,2-cis-Dimethyl-3,6-epoxyhexahydrophthalic anhydride
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| Molecular Formula: |
C10H12O4
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| SMILES: |
[H][C@]12CC[C@]([H])(O1)[C@]1(C)C(=O)OC(=O)[C@]21C
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| Structure: |
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| DrugBank Description: |
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 . 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 . In 1962 however, marketers of cantharidin failed to produce sufficient efficacy data, resulting in the FDA revision of approval of cantharidin .
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 . 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 .
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| CAS Number: |
56-25-7
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| Molecular Weight: |
196.202
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| DrugBank 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 .
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 . 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 .
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 .
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| DrugBank Pharmacology: |
Cantharidin is a natural toxin produced by the blistering beetle that possesses both vesicant (blistering) and keratolytic effects . 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 . 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 . 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 . There is consequently no scarring from the topical application of cantharidin .
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| DrugBank MoA: |
Cantharidin is specifically absorbed by lipids in the membrane of epidermal keratinocytes, where it activates the release of neutral serine proteases . 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 . 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 . A blister(s) at the application site develop within 24 to 48 hours of application and typically resolve within 4 to 7 days . 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 . The blistered lesions ultimately heal without scarring .
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 .
Nevertheless, the fact that little data regarding the pharmacodynamics and pharmacokinetics of cantharidin in the human body exists 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 are strong reasons as to why the compound currently lacks FDA approval is used fairly limitedly for formal therapeutic indications.
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| Targets: |
Aryl hydrocarbon receptor agonist
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| Inclusion Criteria: |
Therapeutic strategy associated
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