Potential of lectin-N-(2-hydroxypropyl)methacrylamide copolymer-drug conjugates for the treatment of pre-cancerous conditions

2001 ◽  
Vol 74 (1-3) ◽  
pp. 283-293 ◽  
Author(s):  
S Wróblewski ◽  
M Berenson ◽  
P Kopečková ◽  
J Kopeček
Keyword(s):  
Drug Conjugates ◽  
Hydroxypropyl Methacrylamide

RAFT-Derived Polymer-Drug Conjugates: Poly(hydroxypropyl methacrylamide) (HPMA)-7-Ethyl-10-hydroxycamptothecin (SN-38) Conjugates

ChemMedChem ◽  
2011 ◽  
Vol 7 (2) ◽  
pp. 281-291 ◽  
Author(s):  
Charlotte C. Williams ◽  
San H. Thang ◽  
Tina Hantke ◽  
Uwe Vogel ◽  
Peter H. Seeberger ◽  
...  
Keyword(s):  
Drug Conjugates ◽  
Hydroxypropyl Methacrylamide ◽  
Polymer Drug Conjugates

Inside Cover: RAFT-Derived Polymer-Drug Conjugates: Poly(hydroxypropyl methacrylamide) (HPMA)-7-Ethyl-10-hydroxycamptothecin (SN-38) Conjugates (ChemMedChem 2/2012)

ChemMedChem ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. 178-178
Author(s):  
Charlotte C. Williams ◽  
San H. Thang ◽  
Tina Hantke ◽  
Uwe Vogel ◽  
Peter H. Seeberger ◽  
...  
Keyword(s):  
Drug Conjugates ◽  
Hydroxypropyl Methacrylamide ◽  
Polymer Drug Conjugates

Polymeric Conjugates of 9-[2-(Phosphonomethoxy)ethyl]purine with Potential Antiviral and Cytostatic Activity

2006 ◽  
Vol 71 (8) ◽  
pp. 1211-1220 ◽  
Author(s):  
Michal Pechar ◽  
Alena Braunová ◽  
Vladimír Šubr ◽  
Karel Ulbrich ◽  
Antonín Holý
Keyword(s):  
Drug Release ◽  
Random Copolymer ◽  
Sustained Drug Release ◽  
Polymer Carrier ◽  
Heterocyclic Base ◽  
Drug Conjugates ◽  
New Family ◽  
Hydroxypropyl Methacrylamide ◽  
Rate Of Hydrolysis

Syntheses and characterization of polymer conjugates of 9-[2-(phosphonomethoxy)ethyl] (PME) derivatives of adenine (PMEA), 2,6-diaminopurine (PMEDAP) and guanine (PMEG) are described. The phosphonate group of these acyclic nucleotide analogues was activated by reaction with triphenylphosphine and di(2-pyridyl) disulfide (TPP-PDS). The activated phosphonate reacted with a random copolymer containing N-(2-hydroxypropyl)methacrylamide (HPMA) and N-(3-methacrylamidopropanoyl)ethane-1,2-diamine (Ma-AP-ED) units. The phosphonamide bond between the nucleotide and polymer carrier proved to be relatively stable at physiological pH 7.4 while at pH 5.0 (corresponding to endosomal or lysosomal compartments of cells) underwent slow hydrolysis. The rate of hydrolysis (drug release) was shown to depend on the detailed structure of the heterocyclic base. The polymer-drug conjugates described in the paper represent a new family of antiviral and cytostatic drugs with potentially improved pharmacokinetics, sustained drug release and diminished non-specific toxicity.

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.

Sign in / Sign up

Export Citation Format

Share Document