picoplatin (AMD 473) / Accelerated Pharma - LARVOL DELTA

Potential common mechanisms between primary Sjögren's syndrome and Hashimoto's thyroiditis: a public databases-based study. (PubMed, Front Genet) - "Guttiferone K and picoplatin may be the candidate drugs for the treatment of pSS and HT...We also gained new insights into the cellular and molecular mechanisms associated with pSS and HT. Based on the key genes and cross-talk genes, we predicted potential drugs and protein domains for pSS and HT."

Journal • Endocrine Disorders • Immunology • Inflammation • Sjogren's Syndrome • Transplant Rejection • CD8 • IFNA1 • IFNG • IL6 • KRAS • PTPRC • STAT1 • STAT5

Cytotoxicity and Binding to DNA, Lysozyme, Ribonuclease A, and Human Serum Albumin of the Diiodido Analog of Picoplatin. (PubMed, Inorg Chem) - "I-picoplatin (IC50 = 3.7-12.4 μM) outperforms picoplatin (IC50 = 11.8-22.6 μM) in the human cancer cell lines used and shows a greater ability to overcome the cisplatin resistance of A2780 ovarian cancer cells than does picoplatin. A low-resolution structure of the I-picoplatin/human serum albumin (HSA) adduct has also been solved. The side chains of His146, Met289, and Met329 are the primary binding sites of the I-picoplatin moieties on HSA."

Journal • Platinum resistant • Cervical Cancer • Oncology • Ovarian Cancer • Solid Tumor

Exploring the Structure-Activity Relationships of Albumin-Targeted Picoplatin-Based Platinum(IV) Prodrugs. (PubMed, Inorg Chem) - "Picoplatin(II) and its derivatives indeed reacted much slower with GSH compared to the respective analogs cisplatin, carboplatin, or oxaliplatin. However, only maleimide-functionalized PicoCarbo(IV) and picoplatin(II) significantly inhibited tumor growth. One possible explanation is that for albumin-binding platinum(IV) prodrugs, the bulky 2-picoline moiety prevents sufficient activation/reduction to unlock their full anticancer potential."

Journal • Oncology

Quantum mechanical approaches and molecular docking studies of platinum based anticancer drugs Satraplatin and picoplatin structures. (PubMed, Biochem Biophys Res Commun) - "DFT studies also show good structural properties and chemical reactivity. From the obtained results, satraplatin and picoplatin were found to have good chemical descriptors and good binding affinity and are best suited for biological molecular targets."

Journal • Oncology

Picoplatin (II)-loaded chitosan nanocomposites as effective drug delivery systems: Preparation, mechanistic investigation of BSA/5-GMP/GSH binding and biological evaluations. (PubMed, Carbohydr Res) - "Since almost all pharmaceuticals work by binding to specific proteins or DNA, the in vitro binding mechanism and affinity of bovine serum albumin (BSA), low molecular building units of nucleic acids (5-GMP), and Glutathione (GSH) (considering that cisplatin resistance could be due to a reaction between cisplatin and GSH) to PPt and PPt@CS NPs were examined using stopped-flow and other spectroscopic approaches. The encapsulation of PPt in CS complex maintained its anticancer activity, as shown by an in vitro cell-survival assay on HepG2 cancer cell lines and also cleavage efficiency toward the minor groove of pBR322 DNA via the hydrolytic way. These findings collectively suggested that inclusion PPt in CS would be an effective strategy to formulate a novel picoplatin formulation intended for use as targeted anticancer treatment."

Journal • Oncology

Picoplatin binding to proteins: X-ray structures and mass spectrometry data on the adducts with lysozyme and ribonuclease A. (PubMed, Dalton Trans) - "With both proteins, picoplatin appears to behave similarly to cisplatin and carboplatin when dissolved in DMSO, whereas it behaves more like oxaliplatin in the absence of the coordinating solvent. This study provides important insights into the pharmacological profile of picoplatin and supports the conclusion that coordinating solvents should not be used to evaluate the biological activities of Pt-based drugs."

Journal • Oncology

From Basics of Coordination Chemistry to Understanding Cisplatin-analogue Pt Drugs. (PubMed, Curr Pharm Des) - "In the development of platinum complexes, strong anti-cancer drug activity, low toxicity, and resistance can be obtained by the application of polynuclear platinum agents, complexes with targeted activity, and nanoparticle formulations. Electronic structure, stereochemical, and thermodynamic properties are essential for understanding the reaction mechanism of platinum complexes."

Journal • Oncology

Thermosensitive Liposomes Encapsulating Nedaplatin and Picoplatin Demonstrate Enhanced Cytotoxicity against Breast Cancer Cells. (PubMed, ACS Omega) - "The cytotoxicity of ND-TSL, p-SC4-ND-TSL, and P-TSL at 40 °C was approximately twice those observed at 37 °C. This study suggests that TSL is a promising nanoplatform for the temperature-triggered release of platinum-based drugs into cancer cells."

Journal • Breast Cancer • Oncology • Solid Tumor

An unexpected in-solution instability of diiodido analogue of picoplatin complicates its biological characterization. (PubMed, Dalton Trans) - "Complex cis-[PtI2(NH3)(pic)] (1; pic = 2-methylpyridine), a diiodido analogue of clinically studied picoplatin (2), is unstable in solution, which is intriguingly connected with the release of its pic ligand. This observation complicates the biological testing of e.g. cytotoxicity in human cancer cells for 1."

Journal • Oncology

Anticancer platinum(II) complexes bearing N-heterocycle rings. (PubMed, Bioorg Med Chem Lett) - "Starting from the pioneering discovery of picoplatin and phenanthriplatin, many efforts were realized by different research groups in the synthesis of different platinum(II) complexes, bearing a N-heterocycle moiety active as anticancer agents in different types of solid tumors. This review deals in particular with both the bifunctional and monofunctional platinum drugs, not only in dichloride platinum(II) complexes, but also in recent advances in modern platinum structures, i.e. cationic ones. Both the in vitro and in vivo studies of these anticancer agents are taken into account, with a special consideration for aggressive and orphan in treatment tumors."

Journal • Review • Oncology • Solid Tumor

A computational study of PAMAM dendrimer interaction with trans isomer of picoplatin anticancer drug. (PubMed, J Mol Graph Model) - "The PAMAM-AMD complexes have shown a significant improvement of structural and electronic properties according to the results obtained from different arrangement of PAMAM G0-AMD complexes; a [G0-AMD (Cl-1)] complex is the preferred adsorption arrangement. As a result, it seems that the zero generation PAMAM dendrimer being combined with the AMD drug is suitable for use in drug delivery."

Journal