Cantharidin

Summary

Cantharidin (CHEMBL48449) is an approved small-molecule EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor targeting PPP2CA and PPP1CA; indicated across 3 conditions including molluscum contagiosum and rheumatoid arthritis.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• Targets: 2 (PPP2CA, PPP1CA)
• Indications: 3 conditions
• Clinical trials: 12
• Chemistry: 196.2 Da · C10H12O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL48449
Name	Cantharidin
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5944
ChEBI	CHEBI:64213
Molecular formula	C10H12O4
Molecular weight	196.2
InChIKey	DHZBEENLJMYSHQ-XCVPVQRUSA-N

SMILES: C[C@@]12[C@H]3CC[C@@H]([C@@]1(C(=O)OC2=O)C)O3

IUPAC name: (1S,2R,6S,7R)-2,6-dimethyl-4,10-dioxatricyclo[5.2.1.02,6]decane-3,5-dione

ChEBI definition: A monoterpenoid with an epoxy-bridged cyclic dicarboxylic anhydride structure secreted by many species of blister beetle, and most notably by the Spanish fly, Lytta vesicatoria. Natural toxin inhibitor of protein phosphatases 1 and 2A.

Pharmacological roles (ChEBI): EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor, herbicide.

Also known as: Cantaridina, Cantharides camphor, Cantharidin, Cantharidine, Cantharidinum, NSC-61805, Ycanth, cantharidin, SID11112131, SID109184, rel-Cantharidin, CANTHARIDIN

Patent coverage: 1,884 distinct patent families (4,679 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 4,678 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
PPP2CA	protein phosphatase 2 catalytic subunit alpha	Inhibition	6.7	84.5%	P67775
PPP1CA	protein phosphatase 1 catalytic subunit alpha	Inhibition	6.8	64.6%	P62136

Broader ChEMBL bioactivity targets: 13 (assay-derived). Sample: Nuclear receptor ROR-gamma, Survival motor neuron protein, Prelamin-A/C, Protein phosphatase 1B, Tyrosine-protein phosphatase non-receptor type 1, Cytochrome P450 1A2, Serine/threonine-protein phosphatase 5, Mitogen-activated protein kinase 1, Cellular tumor antigen p53, Hypoxia-inducible factor 1-alpha.

Bioactivity

ChEMBL activities: 16 potent at pChembl ≥ 5 of 18 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
PPP2CA	6.8	IC50	160	nM	CHEMBL_ACT_24985963
PPP5C	6.4	IC50	400	nM	CHEMBL_ACT_24985975
PPM1B	6.37	IC50	430	nM	CHEMBL_ACT_1200581
TFPI2	6.3	IC50	500	nM	CHEMBL_ACT_26045471
PPP5C	6.22	IC50	600	nM	CHEMBL_ACT_24985967
PPP5C	6.22	IC50	600	nM	CHEMBL_ACT_25477552
LMNA	5.95	Potency	1122	nM	CHEMBL_ACT_3644988
PPP1CC	5.75	IC50	1780	nM	CHEMBL_ACT_259253
PPM1B	5.75	IC50	1780	nM	CHEMBL_ACT_881838
HIF1A	5.6	Potency	2512	nM	CHEMBL_ACT_4132594
HIF1A	5.6	Potency	2512	nM	CHEMBL_ACT_4519363
PTPN1	5.44	IC50	3600	nM	CHEMBL_ACT_746446
P51450	5.3	Potency	5012	nM	CHEMBL_ACT_4093477
MAPK1	5.3	Potency	5012	nM	CHEMBL_ACT_4544705
SMN1	5	Potency	10000	nM	CHEMBL_ACT_3865643
TP53	5	Potency	10000	nM	CHEMBL_ACT_4882579

Target pathways

Aggregated over 2 target gene(s): PPP2CA, PPP1CA.

Top Reactome pathways

43 total, by targets touching each:

Pathway	Targets	Genes
DARPP-32 events	2	PPP1CA, PPP2CA
Inhibition of replication initiation of damaged DNA by RB1/E2F1	1	PPP2CA
Spry regulation of FGF signaling	1	PPP2CA
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1	PPP2CA
Triglyceride catabolism	1	PPP1CA
PP2A-mediated dephosphorylation of key metabolic factors	1	PPP2CA
Degradation of beta-catenin by the destruction complex	1	PPP2CA
Beta-catenin phosphorylation cascade	1	PPP2CA
ERK/MAPK targets	1	PPP2CA
ERKs are inactivated	1	PPP2CA
Downregulation of TGF-beta receptor signaling	1	PPP1CA
MASTL Facilitates Mitotic Progression	1	PPP2CA
Separation of Sister Chromatids	1	PPP2CA
Resolution of Sister Chromatid Cohesion	1	PPP2CA
Initiation of Nuclear Envelope (NE) Reformation	1	PPP2CA
Co-stimulation by CD28	1	PPP2CA
Co-inhibition by CTLA4	1	PPP2CA
Platelet sensitization by LDL	1	PPP2CA
Disassembly of the destruction complex and recruitment of AXIN to the membrane	1	PPP2CA
Signaling by GSK3beta mutants	1	PPP2CA
CTNNB1 S33 mutants aren’t phosphorylated	1	PPP2CA
CTNNB1 S37 mutants aren’t phosphorylated	1	PPP2CA
CTNNB1 S45 mutants aren’t phosphorylated	1	PPP2CA
CTNNB1 T41 mutants aren’t phosphorylated	1	PPP2CA
APC truncation mutants have impaired AXIN binding	1	PPP2CA
AXIN missense mutants destabilize the destruction complex	1	PPP2CA
Truncations of AMER1 destabilize the destruction complex	1	PPP2CA
RHO GTPases Activate Formins	1	PPP2CA
RAF activation	1	PPP2CA
Negative regulation of MAPK pathway	1	PPP2CA

Dominant GO biological processes

GO term	Targets
protein dephosphorylation	2
response to lead ion	2
transcription by RNA polymerase II	2
transcription elongation by RNA polymerase II	2
mitotic cell cycle	1
mesoderm development	1
negative regulation of epithelial to mesenchymal transition	1
regulation of microtubule polymerization	1
negative regulation of hippo signaling	1
intracellular signal transduction	1
peptidyl-threonine dephosphorylation	1
regulation of growth	1
T cell homeostasis	1
regulation of cell differentiation	1
meiotic cell cycle	1

Indications & clinical

Indications

3 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
molluscum contagiosum	4	MONDO:0005855	EFO:0007375
rheumatoid arthritis	1	MONDO:0008383	EFO:0000685

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 12.

Phase distribution

Phase	Trials
PHASE1	4
PHASE2	2
EARLY_PHASE1	2
Not specified	2
PHASE4	1
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03625960	PHASE4	COMPLETED	Cantharone for the Treatment of Perenial Warts
NCT07457918	PHASE3	RECRUITING	Long-Term Follow-up Study of Cantharidin (YCANTH [VP-102/TO-208]) in Patients With Common Warts (Verruca Vulgaris)
NCT02665260	PHASE2	COMPLETED	Safety and Efficacy Study of Topical Cantharidin for the Treatment of Molluscum Contagiosum
NCT03017846	PHASE2	COMPLETED	Safety and Efficacy of Topical Cantharidin for the Treatment of Molluscum Contagiosum, Phase 2
NCT01026064	PHASE1	COMPLETED	Cantharidin-induced Skin Blister for Testing Anti-inflammatory Effects of Macrolides
NCT01762787	PHASE1	COMPLETED	Phase I Methodology Study to Validate the Cantharidin Blister Model in Healthy Volunteers
NCT03306589	PHASE1	COMPLETED	Lipopolysaccharide (LPS) or Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Challenge Study on Healthy Subjects
NCT03426995	PHASE1	TERMINATED	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
NCT05597098	EARLY_PHASE1	RECRUITING	Investigation of the Distinct Mechanisms Involved in Inflammatory Resolution Between Healthy Men and Women
NCT01582321	EARLY_PHASE1	COMPLETED	Investigation of the Influence of Gender on Cardiovascular Function
NCT00667225	Not specified	COMPLETED	Efficacy of Cantharidin in Molluscum Contagiosum
NCT01084824	Not specified	COMPLETED	A Trial Examining the Treatment of Common Warts With Combination Liquid Nitrogen (LN2) and Cantharidin

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

1 molecules share ≥1 primary target. Top 1 by shared-target count:

Molecule	Source	Status	Shared targets
MOLIBRESIB	ChEMBL	Phase 2	PPP1CA