Cisplatin [cis-diamminedichloroplatinum(II)] is a platinum-based anticancer drug commonly used for treatment of different types of cancer, including ovarian, testicular, head and neck or lung carcinomas . Although cisplatin exerts significant anti-tumour activity, cisplatin-based therapies cause numerous side effects, such as nephrotoxicity, neurotoxicity and nausea. The intrinsic as well as acquired resistances to cisplatin-based therapy also represent substantial complications for the treatment of tumours.
For this reason, vast efforts were committed to develop novel platinum-based complexes to overcome platinum resistance, to reduce cisplatin side effects and to introduce novel mechanisms of anti-cancer action. Two derivatives, carboplatin (cis-diammine-(1,1-cyclobutanedicarboxylato)platinum(II)) and oxaliplatin (trans-R,R.cyclohexane-1,2-diammine)oxalatoplatinum(II)), have been introduced . Taken together, these three drugs represent all of the available platinum drugs approved by the Food and Drug Administration for clinical use . In addition to substantial side effects, these three drugs also require intravenous administration, therefore a new generation of platinum drugs represented by satraplatin (JM216) [(OC-6-43)-bis(acetato)amminedichloro(cyclohexylamine)platinum(IV)] has been generated. JM216 represents the first orally administered platinum compound which has been evaluated in clinical trials [2, 4, 5].
LA-12, [(OC-6-43)-bis(acetato)(1-adamantylamine)amminedichloroplatinum (IV)], is a hydrophobic platinum(IV) complex structurally similar to JM216, which contains 1-adamantylamine instead of cyclohexylamine non-leaving ligand  which provides this drug different properties. LA-12 has shown a higher cytotoxicity than JM216 when tested on a panel of 14 cancer cell lines of various origin and different cisplatin sensitivity [6, 7] and no cross-resistance with cisplatin [6, 8]. LA-12 has also displayed (i) higher antitumor activity in comparison with cisplatin and JM216, (ii) favourable pharmacokinetics and (iii) relatively low acute toxicity in a panel of pre-clinical in vivo studies [9–11].
The cytotoxic mode of action of cisplatin is mediated by its interaction with DNA to form DNA adducts, primarily intra-strand crosslink adducts, which activate several signal transduction pathways, including those involving ATR, p53, p73, and MAPK, and culminate in the activation of apoptosis . JM216 has a mechanism of action similar to that of cisplatin, inducing the formation of DNA adducts and inter- and intra-strand crosslinks and resulting in G2 arrest and induction of apoptosis . The principle mechanisms of LA-12 effects are not fully understood to date, although there is some evidence that exposure to LA-12 can disrupt cell proliferation and induce apoptosis more potently than cisplatin in both p53 dependent and independent manners [14, 15]. Interestingly, LA-12 induces unique changes in the profile of gene expression compared to cisplatin, indicating a distinct mode of action resulting in the differential activation of both p53-dependent and p53-independent gene targets .
Besides the well known cisplatin DNA-mediated effect, the other mechanism of cisplatin action was described demonstrating that cisplatin may also disrupt the function of some proteins, including heat shock protein 90 (Hsp90) . According to this study, cisplatin associates with the molecular chaperone Hsp90 and reduces its' chaperone activity. For example, this can result in the degradation of steroid receptors  and/or inhibition of interaction between Hsp90 and inositol hexakisphosphate kinase-2 (IP6K2), which disrupts the inhibitory effect of Hsp90 on IP6K2, leading to increased diphosphoinositol pentakisphosphate (IP7) formation and sensitisation of cancer cells to apoptosis [19, 20].
Since it is supposed that LA-12 undergoes metabolic changes and serves actually as a pro-drug for chemotherapeutically active platinum analogues, it is possible that these active metabolites can interact with proteins analogous to cisplatin, resulting in stronger cytotoxic or cytostatic effects. According to this hypothesis we have analyzed whether LA-12 can bind to Hsp90 resulting in inhibition of its protective chaperoning function such as folding, stabilization, activation and assembly of its "client" proteins.