Drug Information

Drug (ID: DG00838) and It's Reported Resistant Information

• Name: Cantharidin
• Synonyms: Cantharidin; 56-25-7; CANTHARIDINE; Cantharone; Kantaridin; Cantharides camphor; Kantharidin; 1,2-Dimethyl-3,6-epoxyperhydrophthalic anhydride; UNII-IGL471WQ8P; NSC61805; exo-1,2-cis-Dimethyl-3,6-epoxyhexahydrophthalic anhydride; Hexahydro-3a,7a-dimethyl-4,7-epoxyisobenzofuran-1,3-dione; BRN 0085302; AI3-04021; (3ar,4s,7r,7as)-3a,7a-dimethylhexahydro-4,7-epoxy-2-benzofuran-1,3-dione; IGL471WQ8P; CHEMBL48449; 4,7-Epoxyisobenzofuran-1,3-dione, hexahydro-3a,7a-dimethyl-, (3aR,4S,7R,7aS)-rel-; CHEBI:64213; 7a-Dimethylhexahydro-3a,4,7-epoxyisobenzofuran; CAN [Alkaloid]; MFCD00134968; NSC-61805; Cantharidin (USAN); Cantharidin [USAN]; 3a,7a-Dimethylhexahydro-4,7-epoxyisobenzofuran-1,3-dione; NSC 61805; Kantharidin [German]; Caswell No. 157; (3a ,4 ,7 ,7a )-Hexahydro-3a,7a-dimethyl-4,7-epoxyisobenzofuran-1,3-dione; 4,7-Epoxyisobenzofuran-1,3-dione, hexahydro-3a,7a-dimethyl-,(3aR,4S,7R,7aS)-rel-; CCRIS 635; 4,7-Epoxyisobenzofuran-1,3-dione, hexahydro-3a,7a-dimethyl-; 2,3-Dimethyl-7-oxabicyclo(2.2.1)heptane-2,3-dicarboxylic anhydride; 7-Oxabicyclo(2.2.1)heptane-2,3-dicarboxylic anhydride, 2,3-dimethyl-; HSDB 2181; EINECS 200-263-3; EPA Pesticide Chemical Code 013101; Cantaridina; Cantharidinum; CAS-56-25-7; NCGC00016247-01; Prestwick3_000885; (1R,2S,3R,6S)-1,2-Dimethyl-3,6-epoxycyclohexane-1,2-dicarboxylic anhydride; 2,3-dicarboxylic anhydride; Hexahydro-3aalpha,7aalpha-dimethyl-4beta,7beta-epoxyisobenzofuran-1,3-dione; NCIMech_000301; BSPBio_000670; 4,7-Epoxyisobenzofuran-1,3-dione, hexahydro-3a,7a-dimethyl-, (3a-alpha,4-beta,7-beta,7a-alpha); 5-19-05-00051 (Beilstein Handbook Reference); SCHEMBL152262; BPBio1_000738; Cantharides camphor, Cantharone; cid_6708701; HMS2097B12; HMS3412J13; HMS3676J13; 1,6-epoxyperhydrophthalic anhydride; 4,7-Epoxyisobenzofuran-1,3-dione, hexahydro-3a,7a-dimethyl-, (3a.alpha.,4.beta.,7.beta.,7a.alpha.)-; ACT03236; AMY33451; BCP09819; HY-N0209; BDBM50090505; CCG-35382; CCG-36082; WHO 11470; ZINC17611186; AKOS015895930; AC-7967; CS-4979; DB12328; 4,3-dione, hexahydro-3a,7a-dimethyl-; exo-1,6-epoxyhexahydrophthalic anhydride; NCGC00025212-02; NCGC00025212-03; NCGC00025212-04; NCGC00025212-05; NCGC00025212-31; AS-18735; NCI60_005413; WLN: T C555 A AO DVOVTJ C1 G1; AB00513946; Hexahydro-3a,7-epoxyisobenzofuran-1,3-dione; X1105; D11745; 7-Oxabicyclo[2.2.1]heptane-2, 2,3-dimethyl-; 134C968; Q410884; SR-01000597585; SR-01000597585-1; BRD-K80684056-001-01-0; (3aR,4S,7R,7aS)-3a,7a-dimethylhexahydro-4,7-epoxyisobenzofuran-1,3-dione; (1R,2S,6R,7S)-2,6-Dimethyl-4,10-dioxa-tricyclo[5.2.1.0*2,6*]decane-3,5-dione; (1R,7S)-2,6-Dimethyl-4,10-dioxa-tricyclo[5.2.1.0*2,6*]decane-3,5-dione; (1S,2R,6S,7R)-2,6-Dimethyl-4,10-dioxa-tricyclo[5.2.1.0*2,6*]decane-3,5-dione; (1S,2R,6S,7R)-2,6-dimethyl-4,10-dioxatricyclo[5.2.1.02,6]decane-3,5-dione; (1S,3S,4R,7R)-2,6-dimethyl-4,10-dioxa-tricyclo[5.2.1.0-2,6]decane-3,5-dione; 4,3-dione, hexahydro-3a,7a-dimethyl-, (3a.alpha.,4.beta.,7.beta.,7a.alpha.)-; Cantharidin:4,7-Epoxyisobenzofuran-1,3-dione,hexahydro-3a,7a- dimethyl-, (3a,4,7,7a)-,
• Indication:
  In total 1 Indication(s)
  Molluscum contagiosum infection [ICD-11: 1E76]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Fungal infection [ICD-11: 1F29-1F2F]; [1]
• Target: Serine/threonine PP1-alpha (PPP1CA); PP1A_HUMAN; [1]
• Formula: C10H12O4
• IsoSMILES: C[C@@]12[C@H]3CC[C@@H]([C@@]1(C(=O)OC2=O)C)O3
• 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-
• InChIKey: DHZBEENLJMYSHQ-XCVPVQRUSA-N
• PubChem CID: 5944
• ChEBI ID: CHEBI:64213
• TTD Drug ID: D0Z2RA
• DrugBank ID: DB12328

Type(s) of Resistant Mechanism of This Drug

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Fungal infection [ICD-11: 1F29-1F2F]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Transcription factor PDR1 (PDR1) [1]

• Resistant Disease: Sacharomyces cerevisiae infection [ICD-11: 1F29-1F2F]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: TRAMP-C2 cells; Prostate; Homo sapiens (Human); CVCL_3615
• Experiment for Molecule Alteration: Western blot analysis; Fluorescence microscopy assay
• Experiment for Drug Resistance: Spot dilution assay; Liquid media growth curve analysis; Colony forming unit (CFU) assay
• Mechanism Description: ABC transporter Pdr5 is required for cantharidin resistance in Saccharomyces cerevisiae. Cantharidin mediated upregulation of Pdr5 is majorly regulated by Pdr1, cantharidin induced the upregulation of both PDR1 and PDR5 genes., PDR5 is the main cantharidin resistance gene.

Key Molecule: Pleiotropic ABC efflux transporter of multiple drugs (PDR5) [1]

• Resistant Disease: Sacharomyces cerevisiae infection [ICD-11: 1F29-1F2F]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: TRAMP-C2 cells; Prostate; Homo sapiens (Human); CVCL_3615
• Experiment for Molecule Alteration: Western blot analysis; Fluorescence microscopy assay
• Experiment for Drug Resistance: Spot dilution assay; Liquid media growth curve analysis; Colony forming unit (CFU) assay
• Mechanism Description: ABC transporter Pdr5 is required for cantharidin resistance in Saccharomyces cerevisiae. Cantharidin mediated upregulation of Pdr5 is majorly regulated by Pdr1, cantharidin induced the upregulation of both PDR1 and PDR5 genes., PDR5 is the main cantharidin resistance gene.

ICD-02: Benign/in-situ/malignant neoplasm

Cutaneous T-cell lymphoma [ICD-11: 2B00]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Interleukin-2 receptor subunit alpha (IL-2Ralpha) [2]

• Sensitive Disease: Cutaneous T-cell lymphomas [ICD-11: 2B00.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: JAK-STAT signaling pathway; Activation; hsa04630
• Cell Pathway Regulation: AKT/mTOR signaling pathway; Regulation; N.A.
• Cell Pathway Regulation: MAPK signaling pathway; Activation; hsa04010
• In Vitro Model: H9SR cells; embryonic stem cell; Homo sapiens (Human); N.A.
• In Vitro Model: HHSR cells; embryonic stem cell; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay; Immunohistochemistry
• Experiment for Drug Resistance: Flow cytometric assay
• Mechanism Description: Our findings highlight that attenuated ROS accelerates IL-2R translation and therefore brings about aberrant expression of IL-2R protein, leading to overactivation of JAK/STAT, AKT/mTOR and MAPK signaling events, which explains SAHA resistance to CTCL cells. Moreover, cantharidin could overcome SAHA resistance to CTCL by blocking IL-2R-related signaling via ROS dependent manner.

References

• Ref 1: ABC transporter Pdr5 is required for cantharidin resistance in Saccharomyces cerevisiae .Biochem Biophys Res Commun. 2021 May 14;553:141-147. doi: 10.1016/j.bbrc.2021.03.074. Epub 2021 Mar 24. 10.1016/j.bbrc.2021.03.074
• Ref 2: Cantharidin overcomes IL-2Ralpha signaling-mediated vorinostat resistance in cutaneous T-cell lymphoma through reactive oxygen species. J Immunother Cancer. 2024 Jul 14;12(7):e009099.