Orplatna (satraplatin) / Yakult Honsha, Agennix, BMS, Assertio - LARVOL DELTA

Antibacterial compounds against non-growing and intracellular bacteria. (PubMed, NPJ Antimicrob Resist) - "Ten compounds - solithromycin, rifabutin, mitomycin C, and seven fluoroquinolones-have strong bactericidal activity against non-growing P. aeruginosa, killing >4 log10 of bacteria at 2.5 µM. Solithromycin, valnemulin, evofosfamide, and satraplatin are unique in their ability to selectively target non-growing bacteria, exhibiting poor efficacy against growing bacteria. Finally, 31 hit compounds inhibit the growth of intracellular Shigella flexneri in a human enterocyte infection model, indicating their ability to permeate the cytoplasm of host cells. The identified compounds hold potential for treating persistent infections, warranting further comparative studies with current standard-of-care antibiotics."

Journal • Infectious Disease • 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

A Randomised Trial of Cabazitaxel, Docetaxel, Mitoxantrone or Satraplatin (CDMS) Plus Surgery for Prostate Cancer Patients Without Metastasis (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Shanghai Jiao Tong University School of Medicine | Trial completion date: Dec 2025 ➔ Dec 2027 | Trial primary completion date: Dec 2024 ➔ Dec 2026

Surgery • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Nanoparticle-Mediated Delivery of Satraplatin to Overcome Cisplatin Drug Resistance. (PubMed, J Funct Biomater) - "This suggests that SatPt-NPs can overcome drug resistance by evading GSH detoxification. Therefore, SatPt-NPs have the ability to inhibit drug resistance in tumor cells and hold tremendous potential in cancer treatment."

Journal • Oncology • Ovarian Cancer • Solid Tumor

Biomarker Development Trial of Satraplatin in Patients with Metastatic Castration-Resistant Prostate Cancer. (PubMed, Oncologist) - "In this small series, one-third of mCRPC patients responded to platinum-based chemotherapy. Peripheral blood biomarker measurement is feasible in mCRPC, though the biomarkers we investigated were not associated with platinum response. Other biomarkers, such as DNA damage repair mutations, should be evaluated."

Biomarker • Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • TIMP1

Application of Approved Cisplatin Derivatives in Combination Therapy against Different Cancer Diseases. (PubMed, Molecules) - "The aim of current study is the comparison of therapeutic combinations of the currently applied in clinical practice: Cisplatin, Carboplatin, Oxaliplatin, Nedaplatin, Lobaplatin, Heptaplatin, and Satraplatin...The very important strategy for the improvement of the antitumor effect against different cancers is synergistic combination of Cisplatin derivatives with: (1) anticancer agents-Fluorouracil, Gemcitabine, Cytarabine, Fludarabine, Pemetrexed, Ifosfamide, Irinotecan, Topotecan, Etoposide, Amrubicin, Doxorubicin, Epirubicin, Vinorelbine, Docetaxel, Paclitaxel, Nab-Paclitaxel; (2) modulators of resistant mechanisms; (3) signaling protein inhibitors-Erlotinib; Bortezomib; Everolimus; (4) and immunotherapeutic drugs-Atezolizumab, Avelumab, Bevacizumab, Cemiplimab, Cetuximab, Durvalumab, Erlotinib, Imatinib, Necitumumab, Nimotuzumab, Nivolumab, Onartuzumab, Panitumumab, Pembrolizumab, Rilotumumab, Trastuzumab, Tremelimumab, and Sintilimab. An important approach for..."

Combination therapy • IO biomarker • Journal • Review • Oncology

A Randomised Trial of Cabazitaxel, Docetaxel, Mitoxantrone or Satraplatin (CDMS) Plus Surgery for Prostate Cancer Patients Without Metastasis (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Shanghai Jiao Tong University School of Medicine | Trial completion date: Dec 2023 ➔ Dec 2025 | Trial primary completion date: Dec 2022 ➔ Dec 2024

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Satraplatin Demonstrates High Cytotoxic Activity Against Genetically Defined Lymphoid Malignancies. (PubMed, Anticancer Res) - "Satraplatin demonstrated a high cytotoxic activity in genetically well-defined hematological malignancies which is distinct from that of cisplatin. MTAP deficiency was identified as biomarker of enhanced satraplatin efficacy in hematological cancer-derived cell lines. These data in combination with the lipophilicity of satraplatin provide the rationale for targeting specific lymphatic entities such as primary central nervous system lymphoma and cutaneous T-cell lymphoma to improve clinical outcome."

IO biomarker • Journal • CNS Lymphoma • Cutaneous T-cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • T Cell Non-Hodgkin Lymphoma • BCL2 • MTAP

Synthesis, Characterization and Host-Guest Complexation of Asplatin: Improved In Vitro Cytotoxicity and Biocompatibility as Compared to Cisplatin. (PubMed, Pharmaceuticals (Basel)) - "Pt(IV)-based complexes, including satraplatin and asplatin, are promising alternatives that overcome the shortcomings of Pt(II) complexes. In this study, asplatin has been synthesized by fusing acetylsalicylic acid (aspirin) and cisplatin...The outcomes of the present joint theoretical and experimental investigation reinforce the interest in platinum-based anticancer therapeutics when they are protected from undesired interactions and suggest the use of the PSC4 macromolecule as a promising carrier for Pt(IV) anticancer drugs. The formed asplatin/PSC4 inclusion complex may represent an effective chemotherapeutic agent."

Journal • Preclinical • Lung Cancer • Oncology • Solid Tumor

Codelivery of Satraplatin and Aminopyrrolic Receptor with Pluronic F127-based Polyaniline Nanoparticles with NIR Induced release for Combined Chemotherapy. (PubMed, Nanotechnology) - "Biological evaluation shows prepared nanoparticles (Pt-ARNPs) exhibited more effective cytotoxicity (IC50=2.7 μM) against the tested cancer cell lines under laser irradiation, compared with free satraplatin or treatment without NIR. Moreover, Pt-ARNPs showed comparable cytotoxicity against A549 and A549/cis cells, implying that the combination of satraplatin and aminopyrrolic receptor 1with nano carrier might be a promising strategy to reduce platinum resistance and improve therapeutic effect in cancer therapy."

Journal • Oncology

Synthesis of platinum(IV)-acridine anticancer prodrugs (ACS-Fall 2021) - "Platinum-acridine drugs, based on the foundations of cisplatin and carboplatin, are platinum (II) highly potent anticancer drugs, but they are also cytotoxic upon direct testing in animals...An example of this is Satraplatin, whose two axial Diaceto ligands allow for a more successful attachment to targeting or functional groups within the cells as they’re only inert outside of the cells...Reactions were optimized using LCMS to determine conversion rates as well as purity.Further testing will be done to analyze the compound's reduction potential with the heavy metal antioxidant, GSH, found in cells. All three compounds will also be tested to assess their efficacy in lung cancer cell lines as well as in mice to determine their cytotoxicity and side effects in comparison to the precursor P8-A1."

Lung Cancer • Oncology • Solid Tumor

A Randomised Trial of Cabazitaxel, Docetaxel, Mitoxantrone or Satraplatin (CDMS) Plus Surgery for Prostate Cancer Patients Without Metastasis (clinicaltrials.gov) - P1; N=50; Recruiting; Sponsor: Shanghai Jiao Tong University School of Medicine; Trial completion date: Dec 2021 ➔ Dec 2023; Trial primary completion date: Jul 2020 ➔ Dec 2022

Clinical • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Identification of novel resorcinol amide derivatives as potent and specific pyruvate dehydrogenase kinase (PDHK) inhibitors. (PubMed, J Med Chem) - "We demonstrated that the results of PDH assays better correlate with cellular activities than do those of PDHK kinase assays. Furthermore, 19n induces apoptosis of cancer cells via mitochondrial dysfunction, suppresses tumorigenesis and displays a synergistic effect on satraplatin suppression of cancer cell proliferation."

Journal • Oncology

Utilizing A Genomic Sig for "BRCAness" to Eval the Efficacy of Satraplatin in Men With Met. Castration Resistant Prostate Ca (clinicaltrials.gov) - P2; N=13; Completed; Sponsor: Oh, William K., M.D.; Recruiting -> Completed

Trial completion • Biosimilar • Oncology • Ovarian Cancer • Prostate Cancer

Protein expression profiling identifies differential modulation of homologous recombination by platinum-based antitumor agents. (PubMed, Cancer Chemother Pharmacol) - "Oxaliplatin and DAP robustly activate p53 and p21, which downregulate HR proteins to enhance drug activity. More significantly, since oxaliplatin induces a BRCAness state, it may have potential against BRCA-proficient cancers. Satraplatin, on the other hand, resembled cisplatin in its protein expression profile, which indicates that small changes in chemical structure can substantially alter signal transduction pathways to modulate drug activity."

Journal • Oncology • BRCA • BRCA1 • RAD51

Finely-Tuned Asymmetric Platinum(IV) Anticancer Complexes: Structure-Activity Relationship and Application as Orally-available Prodrugs. (PubMed) - ChemMedChem - "We showed that compounds with high lipophilicity result in better anti-proliferative effects in vitro and in vivo with one of the three compounds tested showed better efficacy than satraplatin against an animal colorectal cancer model, owing to its higher solubility and lower reduction rates. Our asymmetric Pt(IV) prodrugs may pave the way for a highly predictable, fine-tuned class of orally-available Pt(IV) prodrugs for against colorectal cancer."

Journal • Biosimilar • Colorectal Cancer • Gastrointestinal Cancer • Oncology

Comparison of the Effect of Platinum (IV) Complexes on Spheroids and Monolayer Culture of HeLa Cells. (PubMed, Bull Exp Biol Med) - "We performed a comparative study of the cytotoxicity of cisplatin, JM216 complex, and aminonitroxyl platinum(IV) complexes for HeLa cells grown in monolayer and 3D culture. Resistance index was 5.0±1.5 for cisplatin and ranged from 1.8 to 2.3 for platinum(IV) complexes. The observed differences are related to different physicochemical properties of the complexes and different mechanisms of their penetration into cells."

Journal • Preclinical

Synthesis of platinum(IV)-acridine anticancer prodrugs (ACS-Sp 2020) - "An example of this type of prodrug is cis,trans,cis-[PtCl2(OAc)2(NH3)(cyclohexylamine)], known as satraplatin, whose two axial acetato (OAc-) ligands confer a high degree of stability to the compound while in circulation...1H NMR spectroscopy and X-ray crystallography were used to characterize the new complexes. Experiments mimicking the compounds’ bio-reduction chemistry under physiologically relevant conditions were also performed and the new compounds were tested in cell proliferation assays to assess their activity in cancer cell lines representing major classes of solid tumors."

Synthesis and Cytotoxicity of Water-Soluble Dual- and Triple-Action Satraplatin Derivatives: Replacement of Equatorial Chlorides of Satraplatin by Acetates. (PubMed, Inorg Chem) - "Pt(II) complexes, such as cisplatin and oxaliplatin, are in widespread use as anticancer drugs. Its good activity against CT26 cells in vitro translated into good in vivo efficacy against the CT26 allograft, an in vivo model with intrinsic satraplatin resistance. This indicates that multiaction Pt(IV) derivatives of diamine dicarboxylates are interesting anticancer drug candidates."

Journal

A Randomised Trial of Cabazitaxel, Docetaxel, Mitoxantrone or Satraplatin (CDMS) Plus Surgery for Prostate Cancer Patients Without Metastasis (clinicaltrials.gov) - P1; N=50; Recruiting; Sponsor: Shanghai Jiao Tong University School of Medicine; Trial completion date: Dec 2020 ➔ Dec 2021; Trial primary completion date: Jul 2019 ➔ Jul 2020

Clinical • Trial completion date • Trial primary completion date

Doubt on a dogma: aquation of equatorial ligands of Pt(IV) complexes under physiological conditions. (PubMed, Angew Chem Int Ed Engl) - "Unexpectedly and in contrast to the current chemical understanding, especially oxaliplatin and satraplatin complexes revealed fast hydrolysis in equatorial position (even in cell culture medium and serum). Notably, the formed hydrolysis products strongly differ in their reduction kinetics, a crucial parameter for activation of Pt(IV) drugs also changing the anticancer potential of the compounds in cell culture. The discovery that intact Pt(IV) complexes can hydrolyze at equatorial position, contradicts the dogma on the general kinetic inertness of Pt(IV) compounds and needs to be considered in the screening and design for novel anticancer drugs."

Journal