Rhodanol synthons for fluorescent labeling and drug conjugates

1996 ◽  
Vol 61 (s1) ◽  
pp. 290-293 ◽  
Author(s):  
Maria Spassova ◽  
Pavol Kois ◽  
Kyoichi Watanabe
Keyword(s):  
Fluorescent Labeling ◽  
Drug Conjugates

ASCO-GU 2019: Metastasierte Urothelkarzinome

2019 ◽  
Vol 10 (03) ◽  
pp. 140-141
Author(s):  
Alexander Kretzschmar
Keyword(s):  
San Francisco ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Chapel Hill ◽  
Antibody Drug

Die Therapielandschaft des metastasierten Urothelkarzinoms hat sich seit der Zulassung der ersten Immun-Checkpoint-Inhibitoren verändert. Die neuen Therapien sind deutlich effektiver, allerdings erreichen die Responseraten der neuen Therapien nur bis zu etwa 30 %, beklagte Prof. Matthew Milowsky, Chapel Hill/USA, auf einer Oral Abstract Session auf dem ASCO-GU. In San Francisco gaben erste Vorträge und Poster bereits einen Einblick, wovon diejenigen Patienten profitieren könnten, die auf die etablierten Chemotherapien und die neuen Immuntherapien nicht ansprechen. Manche Onkologen sprechen bereits von der „Post-Checkpoint-Ära”. Als Kandidaten werden vor allem Antikörper-Wirkstoff-Konjugate (antibody-drug conjugates; ADC) gehandelt – und zwar nicht nur zur Therapie des metastasierten Blasenkarzinoms.

Design, 22-step synthesis, and evaluation of highly potent D-ring modified and linker-equipped analogs of spongistatin 1

2018 ◽  
Author(s):  
James Leighton ◽  
Linda M. Suen ◽  
Makeda A. Tekle-Smith ◽  
Kevin S. Williamson ◽  
Joshua R. Infantine ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Functional Group ◽  
Human Cancer ◽  
Natural Sources ◽  
Spongistatin 1 ◽  
Human Cancer Cell Lines ◽  
Drug Conjugates ◽  
Attractive Candidate ◽  
Complex Fragment ◽  
Antibody Drug

With an average GI50 value against the NCI panel of 60 human cancer cell lines of 0.12 nM, spongistatin 1 is among the most potent anti-proliferative agents ever discovered rendering it an attractive candidate for development as a payload for antibody-drug conjugates and other targeted delivery approaches. It is unavailable from natural sources and its size and complex stereostructure render chemical synthesis highly time- and resource-intensive, however, and its development requires more efficient and step-economical synthetic access. Using novel and uniquely enabling direct complex fragment coupling alkallyl- and crotylsilylation reactions, we have developed a 22-step synthesis of a rationally designed D-ring modified analog of spongistatin 1 that is equipotent with the natural product, and have used that synthesis to establish that the C(15) acetate may be replaced with a linker functional group-bearing ester with only minimal reductions in potency.<br><div><br></div>

ANTIBODY-DRUG CONJUGATES FOR TARGETED CANCER THERAPY

2019 ◽  
Vol 65 (6) ◽  
pp. 777-784
Author(s):  
David Korman
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Gemtuzumab Ozogamicin ◽  
Brentuximab Vedotin ◽  
Cytostatic Agent ◽  
Cytostatic Agents ◽  
Drug Conjugates ◽  
Natural Substances ◽  
Intracellular Release ◽  
High Antitumor Activity

Monoclonal antibody (MAB) conjugates with cytostatic agents (ADC) are intended for selective delivery of a cytostatic agent to a tumor cell. Three ADC have been approved for clinical use (gemtuzumab ozogamicin, brentuximab vedotin, trastuzumab-DM1); a few dozens of other ADC are undergoing clinical trials. Several derivatives of natural substances (antibiotics and inhibitors of microtubules) having a high antitumor activity are used as cytostatic agents included in ADC. They are inapplicable in clinical practice as self-sustained drugs due to their considerable toxicity. Of great importance for the implementation of the ADC effect is the character of a linker connecting MAB with a cytostatic agent and ensuring selective intracellular release after ADC internalization. The structure, mechanisms of action, and the results of clinical trials of a number of ADC are considered here as an illustration (by way of example). The development of ADC can help introduce new effective cytostatic agents into clinical practice.

Nano-Neurotherapeutics (NNTs): An Emergent and Multifaceted Tool for CNS Disorders

2020 ◽  
Vol 21 ◽  
Author(s):  
Aashish Sharma ◽  
Romila Manchanda ◽  
Faheem Hyder Pottoo ◽  
Ghulam Md. Ashraf
Keyword(s):  
Central Nervous System ◽  
Neurological Disorders ◽  
Driving Force ◽  
Treatment Options ◽  
Clinical Aspects ◽  
Future Scenarios ◽  
Cns Disorders ◽  
Drug Conjugates ◽  
Novel Treatment ◽  
Pharmacological Targets

: Impressive research steps have been taken for the treatment of neurological disorders in the last few decades. Still effective treatments of brain related disorders are very less due to problems associated with crossing the blood brain barrier (BBB), non-specific therapies, and delay in functional recovery of central nervous system (CNS) after treatment. Striving for novel treatment options for neurological disorders, nanotechnology-derived materials, and devices have gained the ground due to inherent features of derivatization/encapsulation with drugs as per the neurological ailments and pharmacological targets. Facile developments/syntheses of the nanomaterials-drug conjugates have also been the driving force for researchers to get into this field. Moreover, the tunable size and hydro/lipophilicity of these nanomaterials are the added advantages that make these materials more acceptable for CNS disorders. These nano-neurotherapeutics (NNTs) systems provide the platform for diagnosis, theranostics, treatments, restoration of CNS disorders, and encourage the translation of NNTs from “bench to bedside”. Still, these techniques are in primary stages of medical development. This review describes the latest advancements and future scenarios of developmental and clinical aspects of polymeric NNTs.

Cancer Nanotechnology-An Excursion on Drug Delivery Systems

2019 ◽  
Vol 18 (15) ◽  
pp. 2078-2092 ◽  
Author(s):  
Mala Sharma ◽  
Chitranshu Pandey ◽  
Neha Sharma ◽  
Mohammad A. Kamal ◽  
Usman Sayeed ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Drug Delivery Systems ◽  
Cancer Chemoprevention ◽  
Delivery Systems ◽  
Nanostructured Lipid Carrier ◽  
Nanodrug Delivery ◽  
Drug Conjugates ◽  
Drug Nanoparticles ◽  
Cancer Nanotechnology

Background: Nanotechnology pictures a breakthrough in the domain of cancer therapy owing to its novel properties and functions. This technology is quite amendable as it allows the scientists to engineer drug nanoparticles of dimensions 10nm – 500nm permitting them to pass via leaky vasculature of tumorigenic microenvironment with higher specificity, reduced cytotoxicity and effective release without any after effects. The central part of the review zooms onto the role of nanoparticles and their targeted delivery for the cure of cancer. Methods: The novel and various versatile nanoparticle platforms viz. polymeric (drug-conjugates, micelles, dendrimers), Lipid-based (liposomes, solid nanoparticle, nanostructured lipid carrier, lipid-polymer hybrid), and stimuli-sensitive (thermoresponsive, ultrasound, pH-responsive, hydrogel) etc. have been designed for a persistent, précised nanodrug delivery and the co-delivery of collegial drug conjugates leading to the formation of safer release of myriad of drugs for cancer chemoprevention. Results: The review concerns about tracing and detailing the drug delivery systems of cancer nanotechnology. Conclusion: Nanotechnology is bestowed with the design, depiction, fabrication, and application of nanostructures, and devices with their controlled delivery together with the imaging of the selected target site and drug release at the specific site of action.

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