ArticleInvestigational new drugs2008
The novel alkylating prodrug J1: diagnosis directed activity profile ex vivo and combination analyses in vitro.
Article in Investigational new drugs, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Patient-reported outcomes in relapsed/refractory multiple myeloma treated with melflufen plus dexamethasone: analyses from the Phase II HORIZON study.British journal of haematology · 2022Trial
- Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Trial
- First-in-human, phase I/IIa clinical study of the peptidase potentiated alkylator melflufen administered every three weeks to patients with advanced solid tumor malignancies.Investigational new drugs · 2015Trial
- Assessment of Oxidative Stress-Induced Oral Epithelial Toxicity.Biomolecules · 2023Article
- Article
- Drug resistance in multiple myeloma: Soldiers and weapons in the bone marrow niche.Frontiers in oncology · 2022Review
- Novel Non-Immunologic Agents for Relapsed and Refractory Multiple Myeloma: A Review Article.Cancers · 2021Review
- Article
- Spotlight on Melphalan Flufenamide: An Up-and-Coming Therapy for the Treatment of Myeloma.Drug design, development and therapy · 2021Review
- Melflufen: A Peptide-Drug Conjugate for the Treatment of Multiple Myeloma.Journal of clinical medicine · 2020Review
- Melflufen, a peptide-conjugated alkylator, is an efficient anti-neo-plastic drug in breast cancer cell lines.Cancer medicine · 2020Article
- Review
- In vitro and in vivo anti-leukemic activity of the peptidase-potentiated alkylator melflufen in acute myeloid leukemia.Oncotarget · 2017Article
- Preclinical activity of melflufen (J1) in ovarian cancer.Oncotarget · 2016Article
- In vitro and in vivo activity of melflufen (J1)in lymphoma.BMC cancer · 2016Article
- Aminopeptidase N (CD13) as a target for cancer chemotherapy.Cancer science · 2011Review
- In vitro activity of bortezomib in cultures of patient tumour cells--potential utility in haematological malignancies.Medical oncology (Northwood, London, England) · 2009Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe dipeptide J1 acts as a prodrug of melphalan with a significant increased potency in vitro resulting from activation by cellular aminopeptidases. The current study was performed to evaluate the ex vivo profile of J1 using 176 primary tumor cell cultures from patients. In addition, the activity of J1 in combination with eight standard drugs, representing different mechanistic classes, was studied in nine different human tumor cell lines of different histopathological origin.
methodsEx vivo evaluation of tumor type selectivity, was performed using the established fluorometric microculture cytotoxicity assay (FMCA). Combinations between J1 and eight standard chemotherapeutic drugs were analyzed using the median-effect method.
resultsThe prodrug J1 expressed approximately 50- to 100-fold higher potency but similar activity profile as that of its metabolite, melphalan. The difference was greater in some diagnoses (e.g. breast cancer, NHL and AML), and exceptionally high in some breast cancer samples with aggressive phenotypes. Combination analysis of J1 and standard chemotherapeutics yielded several potentially additive and synergistic interactions, most striking for etoposide with significant synergism in all studied cell lines.
conclusionsIn conclusion, the ex vivo profile suggests that further evaluation of J1 as the alkylating agent in for example aggressive breast cancer might be of particular interest, preferentially in combination with DNA-topoisomerase II inhibitors like etoposide.
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