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Chemical structure of Dicycloplatin
Clinical data
Trade namesDicycloplatin
Other namesPlatinum(2+) 1-carboxycyclobutanecarboxylate ammoniate (1:2:2), 1,1-Cyclobutanedicarboxylic acid, compd. with (sp-4-2)-diammine(1,1-cyclobutanedi(carboxylato-kappaO)(2-))platinum (1:1)
Routes of
Pharmacokinetic data
Bioavailability100% (IV)
Protein binding< 88.7%
Elimination half-life24.49 - 108.93 hours
  • azane;cyclobutane-1,1-dicarboxylate;cyclobutane-1,1-dicarboxylic acid;platinum(2+)
CAS Number
Chemical and physical data
Molar mass515.382 g·mol−1
3D model (JSmol)
  • C1CC(C1)(C(=O)O)C(=O)O.C1CC(C1)(C(=O)[O-])C(=O)[O-].N.N.[Pt+2]

  • coordination form: C0CCC0C4[C-]1O[H+]O[C-](O[H+][NH2+]2)C0(CCC0)[C-](O[H+][NH2+]3)O[H+]O[C-]4O[Pt-2]23O1
  • InChI=InChI=1S/2C6H8O4.2H3N.Pt/c2*7-4(8)6(5(9)10)2-1-3-6;;;/h2*1-3H2,(H,7,8)(H,9,10);2*1H3;/q;;;;+2/p-2 checkY

Dicycloplatin is a chemotherapy medication used to treat a number of cancers which includes the non-small-cell lung carcinoma and prostate cancer.[1]

Some side effects which are observed from the treatment by dicycloplatin are nausea, vomiting, thrombocytopenia, neutropenia, anemia, fatigue, loss of appetite, liver enzyme elevation and alopecia. The drug is a platinum-based antineoplastic, and it works by causing mitochondrial dysfunction which leads to cell death.[2]

Dicycloplatin was developed in China and it was used for phase I human trial clinical in 2006. The drug was approved for chemotherapy by the Chinese FDA in 2012.[3]

Medical uses

Dicycloplatin can inhibit the proliferation of tumor cells via the induction of apoptosis. It is used to treat a number types of cancer which are non-small-cell lung carcinoma and prostate cancer.[2]

Side effects

Similar to cisplatin and carboplatin, dicycloplatin also contains some side effects, which are nausea, vomiting, thrombocytopenia, neutropenia, anemia, fatigue, loss of appetite, liver enzyme elevation, and alopecia. However, with doses up to 350 mg/m(2), there is no significant toxicity; these effects are observed only at higher doses. Furthermore, the nephrotoxicity of dicycloplatin is reported to be less than that of cisplatin, and its myelosuppressive potency is similar to that of carboplatin.[4]

Chemical structure

Dicycloplatin consists of carboplatin and cyclobutane-1,1-dicarboxylic acid (CBDC) linked by the hydrogen bond. In the structure of dicycloplatin, there are two types of bond: O-H...O is the bond between the hydroxyl group of CBDC with carboxyl oxygen atom. It creates the one-dimensional polymer chain of carboplatin and CBDC. The second one is N-H...O which links between the ammonia group of carboplatin and oxygen of CBDC. It forms the two-dimensional polymer chain of carboplatin and CBDC. In aqueous solution, the 2D-hydrogen bonded polymeric structure of dicycloplatin is destroyed. Firstly, the bond between ammonia group of carboplatin and oxygen of CBDC breaks, thus inducing the formation of one-dimensional dicycloplatin. After that, the strong hydrogen bond breaks and creates an intermediate state of dicycloplatin. Finally, the rearrangement of different orientation of carboplatin and CBDC leads to the formation of intramolecular hydrogen bond and a supramolecule of dicycloplatin with two O-H...O and N-H...O is created.[5]

Mechanism of action

Similar to carboplatin, dicycloplatin inhibits the proliferation of cancer cells by inducing cell apoptosis. When treated with dicycloplatin, some changes in the properties of Hep G2 cells are observed: the declination of Mitochondria Membrane Potential, the release of cytochrome c from mitochondria to cytosol, the activation of caspase-9, caspase-3 and the decrease of Bcl-2.[2] Those phenomena indicate the role of mitochondrial in the apoptosis by intrinsic way.[6] Furthermore, the increase in caspase-8 activation is also observed. This can stimulate the apoptosis by activating downstream caspase-3[7] or by cleaving Bid.[8] As a result, the cleavage of Bid (tBid) transfers to the mitochondria and induce mitochondrial dysfunction which promotes the release of cytochrome c from mitochondria to cytosol.[9] From the dicycloplatin-treated Hep G2 cell, an excessive amount of reactive oxygen species was detected,[2] which plays an important role in the release of cytochrome c. In the mitochondria, the release of hemoprotein happens through 2-step process: Firstly, the dissociation of cytochrome c from its binding to cardiolipin happens. Due to the reactive oxygen species, the cardiolipin is oxidized, thus reducing the cytochrome c binding and increase the concentration of free cytochrome c[10]


  1. ^ Zhao D, Zhang Y, Xu C, Dong C, Lin H, Zhang L, et al. (August 2012). "Pharmacokinetics, tissue distribution, and plasma protein binding study of platinum originating from dicycloplatin, a novel antitumor supramolecule, in rats and dogs by ICP-MS". Biological Trace Element Research. 148 (2): 203–8. doi:10.1007/s12011-012-9364-2. PMID 22367705. S2CID 16035022.
  2. ^ a b c d Li GQ, Chen XG, Wu XP, Xie JD, Liang YJ, Zhao XQ, et al. (November 2012). "Effect of dicycloplatin, a novel platinum chemotherapeutical drug, on inhibiting cell growth and inducing cell apoptosis". PLOS ONE. 7 (11): e48994. Bibcode:2012PLoSO...748994L. doi:10.1371/journal.pone.0048994. PMC 3495782. PMID 23152837.
  3. ^ Yu JJ, Yang X, Song Q, Mueller MD, Remick SC (January 2014). "Dicycloplatin, a novel platinum analog in chemotherapy: synthesis of chinese pre-clinical and clinical profile and emerging mechanistic studies". Anticancer Research. 34 (1): 455–63. PMID 24403501.
  4. ^ Li S, Huang H, Liao H, Zhan J, Guo Y, Zou BY, et al. (February 2013). "Phase I clinical trial of the novel platin complex dicycloplatin: clinical and pharmacokinetic results". International Journal of Clinical Pharmacology and Therapeutics. 51 (2): 96–105. doi:10.5414/CP201761. PMID 23127487.
  5. ^ Yang X, Jin X, Song Q, Tang K, Yang Z, Zhang X, Tang Y (June 2010). "Structural studies of dicycloplatin, an antitumor supramolecule". Science China Chemistry. 53 (6): 1346–1351. doi:10.1007/s11426-010-3184-z. S2CID 97893314.
  6. ^ Kumar R, Herbert PE, Warrens AN (September 2005). "An introduction to death receptors in apoptosis". International Journal of Surgery. 3 (4): 268–77. doi:10.1016/j.ijsu.2005.05.002. PMID 17462297.
  7. ^ Yang BF, Xiao C, Li H, Yang SJ (December 2007). "Resistance to Fas-mediated apoptosis in malignant tumours is rescued by KN-93 and cisplatin via downregulation of c-FLIP expression and phosphorylation". Clinical and Experimental Pharmacology & Physiology. 34 (12): 1245–51. doi:10.1111/j.1440-1681.2007.04711.x. PMID 17973862. S2CID 40501734.
  8. ^ Blomgran R, Zheng L, Stendahl O (May 2007). "Cathepsin-cleaved Bid promotes apoptosis in human neutrophils via oxidative stress-induced lysosomal membrane permeabilization". Journal of Leukocyte Biology. 81 (5): 1213–23. doi:10.1189/jlb.0506359. PMID 17264306. S2CID 13209075.
  9. ^ Yin XM (March 2006). "Bid, a BH3-only multi-functional molecule, is at the cross road of life and death". Gene. 369: 7–19. doi:10.1016/j.gene.2005.10.038. PMID 16446060.
  10. ^ Ott M, Gogvadze V, Orrenius S, Zhivotovsky B (May 2007). "Mitochondria, oxidative stress and cell death". Apoptosis. 12 (5): 913–22. doi:10.1007/s10495-007-0756-2. PMID 17453160.