ID: ALA1237212

Max Phase: Phase

Molecular Formula: C8H8O4

Molecular Weight: 168.15

Molecule Type: Small molecule

Representations

Synonyms (5): Demethylcantharidin | Isocantharidin | Norcantharidin | NSC-14003 | NSC-59023
Synonyms from Alternative Forms(5):

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

Molecule Features

Natural Product: Yes

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: Yes

Availability: No

Prodrug: No

Properties

Molecular Weight: 168.15

Molecular Weight (Monoisotopic): 168.0423

AlogP: -0.14

#Rotatable Bonds: 0

Polar Surface Area: 52.60

Molecular Species: NEUTRAL

HBA: 4

HBD: 0

#RO5 Violations: 0

HBA (Lipinski): 4

HBD (Lipinski): 0

#RO5 Violations (Lipinski): 0

CX Acidic pKa:

CX Basic pKa:

CX LogP: -0.05

CX LogD: -0.05

Aromatic Rings: 0

Heavy Atoms: 12

QED Weighted: 0.37

Np 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,  6  (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,  7  (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,  7  (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.,  5  (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.,  3  (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, 

Source

Source(2):

• Scientific Literature
• Clinical Candidates