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For the past 40 years, metal-based drugs have been widely used for the treatment of cancer. Cisplatin and follow-up drugs carboplatin (ParaplatinTM) and oxaliplatin (EloxatinTM) have been the gold standard for metallodrugs in clinical settings as antineoplastic agents. While effective, these drugs (either alone or in combination therapy) have faced a number of clinical challenges resulting from their limited spectrum of activity, high toxicity leading to significant side effects, resistance, poor water solubility, low bioavailability and short circulating time. In the past 10 years, various unconventional non-platinum metal-based agents have emerged as a potential alternative for cancer treatment. These compounds are highly effective and selective in cancers resistant to cisplatin and other chemotherapeutic agents. Research in this area has recently exploded with a relevant number of patents and clinical trials, in addition to reports in scientific journals. Furthermore, in parallel to the synthesis of coordination and organometallic compounds comprising many different metals and unconventional platinum-based derivatives, researchers are focused on optimizing mechanistic and pharmacological features of promising drug candidates. This Special Issue aims to highlight the latest advances in anticancer metallodrugs with a focus on unconventional anticancer agents, as well as novel activation, targeting and delivery strategies aimed at improving their pharmacological profile.

?–? stacking --- encapsulation --- n/a --- oxindolimine–metal complexes --- cyclodextrin --- platinum iodido complexes --- distribution coefficient --- antiproliferative activity --- anticancer agents --- nanotubes --- ruthenium --- platinum --- Log kw --- nanoparticles --- drug discovery --- metal complex --- metallodrugs --- isatin-derived ligands --- anticancer drug --- upconverting nanoparticles --- pyridine benzimidazole --- dendrimers --- liposomes --- thiophene --- angiogenesis --- micelles --- HSA oxidation --- platinum(IV) --- imaging --- chromatographic lipophilicity parameter --- amidophosphine --- copper and iron chelators in cancer --- Log P --- biomacromolecules --- bones --- DNA cleavage --- stopped-flow spectroscopy --- silver --- phosphonates --- transmetalation --- metallomics --- MRI --- fluorescence quenching --- partition coefficient --- gold fingers --- anticancer --- HSA binding --- gold --- ?0 --- targeting --- metastasis --- DNA interaction --- antimigration --- cytotoxicity --- HPLC --- ruthenium complexes --- zinc finger proteins --- Gold(III) complexes --- aquaporins --- antiproliferative --- protein-DNA recognition --- photoactivation --- lipophilicity --- cancer --- 1-methylcytosine --- PET --- ?-? stacking --- oxindolimine-metal complexes

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It is now clearly established that some proteins or protein regions are devoid of any stable secondary and/or tertiary structure under physiological conditions, but still possess fundamental biological functions. These intrinsically disordered proteins (IDPs) or regions (IDRs) have peculiar features due to their plasticity such as the capacity to bind their biological targets with high specificity and low affinity, and the possibility of interaction with numerous partners. A correlation between intrinsic disorder and various human diseases such as cancer, diabetes, amyloidoses and neurodegenerative diseases is now evident, highlighting the great importance of the topic. In this volume, we have collected recent high-quality research about IDPs and human diseases. We have selected nine papers which deal with a wide range of topics, from neurodegenerative disease to cancer, from IDR-mediated interactions to bioinformatics tools, all related to IDP peculiar features. Recent advances in the IDPs/IDRs issue are here presented, contributing to the progress of knowledge of the intrinsic disorder field in human disease.

alpha-synuclein --- NMR --- secondary structure propensity --- pre-structured motifs (PreSMos) --- intrinsically disordered protein --- ubiquitin-proteasome system --- intrinsically disordered proteins --- protein misfolding --- molecular recognition features --- cancer --- neurodegenerative diseases --- protein degradation --- EPR spectroscopy --- isothermal titration calorimetry --- protein-ligand interaction --- site-directed spin labeling --- protein structural dynamics --- WASp interacting protein --- protein–protein interactions --- actin --- cytoskeleton remodeling --- SH3 domain --- proline-rich motif --- single nucleotide variants --- interface core and rim --- human disease --- intrinsically disordered regions --- linear motifs --- gene duplications --- de novo --- evolutionary origin --- circular dichroism --- flexibility --- fluorescence --- importin --- isothermal titration calorimetry (ITC) --- molecular docking --- nuclear magnetic resonance (NMR) --- nuclear protein 1 (NPR1) --- peptide --- Methyl-CpG-binding protein 2 (MeCP2) --- Rett syndrome --- intrinsically disordered protein (IDP) --- protein stability --- protein-DNA interaction --- proteostasis --- ubiquitin independent degradation --- NADH-26S proteasome --- n/a --- protein-protein interactions