4,10-Dioxa-tricyclo[5.2.1.0*2,6*]decane-3,5-dione

ID: ALA1237212

Chembl Id: CHEMBL1237212

PubChem CID: 12251907

Max Phase: Phase

Molecular Formula: C8H8O4

Molecular Weight: 168.15

Molecule Type: Small molecule

Associated Items:

Names and Identifiers

Synonyms: Demethylcantharidin | Isocantharidin | Norcantharidin | NSC-14003 | NSC-59023 | Isocantharidin|Demethylcantharidin|NSC-14003|NSC-59023|CHEMBL1237212|BDBM50366474

Canonical SMILES:  O=C1OC(=O)[C@H]2[C@@H]1[C@H]1CC[C@H]2O1

Standard InChI:  InChI=1S/C8H8O4/c9-7-5-3-1-2-4(11-3)6(5)8(10)12-7/h3-6H,1-2H2/t3-,4-,5-,6+/m1/s1

Standard InChI Key:  JAABVEXCGCXWRR-KAZBKCHUSA-N

Alternative Forms

  1. Parent:

    ALA1237212

    NORCANTHARIDIN

Associated Targets(Human)

Jurkat (10389 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PPM1B Tchem Protein phosphatase 2C beta (71 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PPP2CA Tchem Serine/threonine protein phosphatase 2A, catalytic subunit, alpha isoform (25 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
A2780 (11979 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ADDP cell line (11 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
143B (353 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HCT-116 (91556 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HT-29 (80576 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
G-401 (156 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
NCI-H460 (60772 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SW480 (6023 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
MCF7 (126967 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
A-431 (6446 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
DU-145 (51482 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HepG2 (196354 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SK-HEP1 (1155 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SLCO1B3 Tchem Solute carrier organic anion transporter family member 1B3 (2517 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SLCO1B1 Tchem Solute carrier organic anion transporter family member 1B1 (2672 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
A549 (127892 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HeLa (62764 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

Serine-threonine protein phosphatase 2A regulatory subunit (96 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Ppp2r1a Serine/threonine protein phosphatase 2A, 65 kDa regulatory subunit A, alpha isoform (4 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Mus musculus (284745 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
L1210 (27553 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Hepatocyte (2621 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Plasmodium falciparum (966862 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Danio rerio (3092 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Escherichia coli (133304 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Molecule Features

Natural Product: YesOral: NoChemical Probe: NoParenteral: No
Molecule Type: Small moleculeTopical: NoFirst In Class: NoBlack Box: No
Chirality: YesAvailability: NoProdrug: No

Drug Indications

MESH IDMESH Heading EFO IDsEFO TermsMax Phase for IndicationReferences

Mechanisms of Action

Mechanism of ActionAction Typetarget IDTarget NameTarget TypeTarget OrganismBinding Site NameReferences

Calculated Properties

Molecular Weight: 168.15Molecular Weight (Monoisotopic): 168.0423AlogP: -0.14#Rotatable Bonds:
Polar Surface Area: 52.60Molecular Species: NEUTRALHBA: 4HBD:
#RO5 Violations: HBA (Lipinski): 4HBD (Lipinski): #RO5 Violations (Lipinski):
CX Acidic pKa: CX Basic pKa: CX LogP: -0.05CX LogD: -0.05
Aromatic Rings: Heavy Atoms: 12QED Weighted: 0.37Np Likeness Score: 1.09

References

1. McCluskey A, Taylor C, Quinn RJ, Suganuma M, Fujiki H.  (1996)  Inhibition of protein phosphatase 2A by cantharidin analogues,  (9): [10.1016/0960-894X(96)00166-7]
2. McCluskey A, Bowyer MC, Collins E, Sim ATR, Sakoff JA, Baldwin ML..  (2000)  Anhydride modified cantharidin analogues: synthesis, inhibition of protein phosphatases 1 and 2A and anticancer activity.,  10  (15): [PMID:10937725] [10.1016/s0960-894x(00)00323-1]
3. Sodeoka M, Baba Y, Kobayashi S, Hirukawa N.  (1997)  Structure-activity relationship of cantharidin derivatives to protein phosphatases 1, 2A1, and 2B,  (14): [10.1016/S0960-894X(97)00316-8]
4. Ho YP, To KK, Au-Yeung SC, Wang X, Lin G, Han X..  (2001)  Potential new antitumor agents from an innovative combination of demethylcantharidin, a modified traditional Chinese medicine, with a platinum moiety.,  44  (13): [PMID:11405643] [10.1021/jm000476t]
5. Enz A, Zenke G, Pombo-Villar E.  (1997)  7-Oxa[2.2.1]bicycloheptane-2,3-dicarboxylic acid derivatives as phosphatase inhibitors,  (19): [10.1016/S0960-894X(97)10005-1]
6. McCluskey A, Walkom C, Bowyer MC, Ackland SP, Gardiner E, Sakoff JA..  (2001)  Cantharimides: a new class of modified cantharidin analogues inhibiting protein phosphatases 1 and 2A.,  11  (22): [PMID:11677131] [10.1016/s0960-894x(01)00594-7]
7. McCluskey A, Keane MA, Walkom CC, Bowyer MC, Sim AT, Young DJ, Sakoff JA..  (2002)  The first two cantharidin analogues displaying PP1 selectivity.,  12  (3): [PMID:11814804] [10.1016/s0960-894x(01)00777-6]
8. Hart ME, Chamberlin AR, Walkom C, Sakoff JA, McCluskey A..  (2004)  Modified norcantharidins; synthesis, protein phosphatases 1 and 2A inhibition, and anticancer activity.,  14  (8): [PMID:15050639] [10.1016/j.bmcl.2004.01.093]
9. Hill TA, Stewart SG, Sauer B, Gilbert J, Ackland SP, Sakoff JA, McCluskey A..  (2007)  Heterocyclic substituted cantharidin and norcantharidin analogues--synthesis, protein phosphatase (1 and 2A) inhibition, and anti-cancer activity.,  17  (12): [PMID:17451951] [10.1016/j.bmcl.2007.03.093]
10. Hill TA, Stewart SG, Ackland SP, Gilbert J, Sauer B, Sakoff JA, McCluskey A..  (2007)  Norcantharimides, synthesis and anticancer activity: Synthesis of new norcantharidin analogues and their anticancer evaluation.,  15  (18): [PMID:17606377] [10.1016/j.bmc.2007.06.034]
11. Stewart SG, Hill TA, Gilbert J, Ackland SP, Sakoff JA, McCluskey A..  (2007)  Synthesis and biological evaluation of norcantharidin analogues: towards PP1 selectivity.,  15  (23): [PMID:17870547] [10.1016/j.bmc.2007.08.028]
12. Thaqi A, Scott JL, Gilbert J, Sakoff JA, McCluskey A..  (2010)  Synthesis and biological activity of Delta-5,6-norcantharimides: importance of the 5,6-bridge.,  45  (5): [PMID:20153915] [10.1016/j.ejmech.2010.01.004]
13. Yeh CB, Su CJ, Hwang JM, Chou MC..  (2010)  Therapeutic effects of cantharidin analogues without bridging ether oxygen on human hepatocellular carcinoma cells.,  45  (9): [PMID:20691337] [10.1016/j.ejmech.2010.05.053]
14. Yuan J, Johnson RL, Huang R, Wichterman J, Jiang H, Hayton K, Fidock DA, Wellems TE, Inglese J, Austin CP, Su XZ..  (2009)  Genetic mapping of targets mediating differential chemical phenotypes in Plasmodium falciparum.,  (10): [PMID:19734910] [10.1038/nchembio.215]
15. Diamandis P, Wildenhain J, Clarke ID, Sacher AG, Graham J, Bellows DS, Ling EK, Ward RJ, Jamieson LG, Tyers M, Dirks PB..  (2007)  Chemical genetics reveals a complex functional ground state of neural stem cells.,  (5): [PMID:17417631] [10.1038/nchembio873]
16. Bajsa J, McCluskey A, Gordon CP, Stewart SG, Hill TA, Sahu R, Duke SO, Tekwani BL..  (2010)  The antiplasmodial activity of norcantharidin analogs.,  20  (22): [PMID:20888768] [10.1016/j.bmcl.2010.09.004]
17. Robertson MJ, Gordon CP, Gilbert J, McCluskey A, Sakoff JA..  (2011)  Norcantharimide analogues possessing terminal phosphate esters and their anti-cancer activity.,  19  (18): [PMID:21855357] [10.1016/j.bmc.2011.01.031]
18. De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP..  (2013)  Structure-based identification of OATP1B1/3 inhibitors.,  83  (6): [PMID:23571415] [10.1124/mol.112.084152]
19. Zhao J, Guan XW, Chen SW, Hui L..  (2015)  Synthesis and biological evaluation of norcantharidin derivatives as protein phosphatase-1 inhibitors.,  25  (2): [PMID:25466711] [10.1016/j.bmcl.2014.11.032]
20. Yan D, Ni LK, Chen HL, Chen LC, Chen YH, Cheng CC..  (2016)  Amphiphilic nanoparticles of resveratrol-norcantharidin to enhance the toxicity in zebrafish embryo.,  26  (3): [PMID:26764188] [10.1016/j.bmcl.2015.12.099]
21. Han HW, Qiu HY, Hu C, Sun WX, Yang RW, Qi JL, Wang XM, Lu GH, Yang YH..  (2016)  Design, synthesis and anti-cancer activity evaluation of podophyllotoxin-norcantharidin hybrid drugs.,  26  (14): [PMID:27262599] [10.1016/j.bmcl.2016.05.063]
22. Unpublished dataset,