LU103793, a synthetic analogue of dolastatin 15, showed interesting pre-clinical activity in melanoma xenografts. In this phase II multicentre trial, 80 chemotherapy-naïve patients with metastatic melanoma received a total of 218 cycles of treatment. The response rate showed one complete and three partial responses of median duration six months (range 3-9.1). Toxicity was moderate, mostly haematological (neutropenia grade 4 in 16%, grade 3 in 3%). There were no significant problems with hypertension or other non-haematological toxicities.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1023/a:1011194910571 | DOI Listing |
Pharmaceuticals (Basel)
December 2024
Department "Pharmacology, Pharmacotherapy and Toxicology", Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria.
The present review provides a detailed and comprehensive discussion on antibody-drug conjugates (ADCs) as an evolving new modality in the current therapeutic landscape of malignant diseases. The principle concepts of targeted delivery of highly toxic agents forsaken as stand-alone drugs are examined in detail, along with the biochemical and technological tools for their successful implementation. An extensive analysis of ADCs' major components is conducted in parallel with their function and impact on the stability, efficacy, safety, and resistance profiles of the immunoconjugates.
View Article and Find Full Text PDFNat Prod Rep
December 2024
Department of Medicinal Chemistry and Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, 1345 Center Drive, Gainesville, Florida 32610, USA.
Covering 2010-April 2024There have been tremendous new discoveries and developments since 2010 in anticancer research based on marine cyanobacteria. Marine cyanobacteria are prolific sources of anticancer natural products, including the tubulin agents dolastatins 10 and 15 which were originally isolated from a mollusk that feeds on cyanobacteria. Decades of research have culminated in the approval of six antibody-drug conjugates (ADCs) and many ongoing clinical trials.
View Article and Find Full Text PDFMol Divers
July 2024
Department of Physiology, School of Basic Medical Science, Central South University, Changsha, 410078, Hunan, China.
Cyclin-dependent kinases (CDKs) are overexpressed in tumor cells, and their aberrant activation can promote the progression of non-small-cell lung cancer (NSCLC). We utilized structure-based virtual screening and experimental validation to screen for potential CDKs antagonists among TargetMol natural products. Molecular docking and molecular dynamics simulation results indicate that Dolastatin 10 exhibits strong interactions with multiple subtypes of CDKs (CDK1, CDK2, CDK3, CDK4, and CDK6), forming stable CDKs-Dolastatin 10 complex compounds.
View Article and Find Full Text PDFBioorg Med Chem
July 2024
Department of Chemical Sciences, Ariel University, Ariel 40700, Israel. Electronic address:
Dolastatin 10 (Dol-10), a natural marine-source pentapeptide, is a powerful antimitotic agent regarded as one of the most potent anticancer compounds found to date. Dol-10 however, lacks chemical conjugation capabilities, which restricts the feasibility of its application in targeted drug therapy. This limitation has spurred the prospect that chemical structure of the parent molecule might allow conjugation of the derivatives to drug carriers such as antibodies.
View Article and Find Full Text PDFRSC Adv
March 2024
Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital, Southern Medical University Guangzhou 510091 China
Dolastatin derivatives possess excellent anticancer activity and have been translated into clinical trials for cancer therapy. Drug delivery systems enable dolastatin derivatives to break the limitation of instability during blood circulation and ineffective cell internalization in the application. Nevertheless, their potential has not been thoroughly established because of the limited loading efficacy and complicated chemical modification.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!