Antitumor activity of the alkylating oligopeptides J1 (L-melphalanyl-p-L-fluorophenylalanine ethyl ester) and P2 (L-prolyl-m-L-sarcolysyl-p-L-fluorophenylalanine ethyl ester): comparison with melphalan

@article{Gullbo2003AntitumorAO,
  title={Antitumor activity of the alkylating oligopeptides J1 (L-melphalanyl-p-L-fluorophenylalanine ethyl ester) and P2 (L-prolyl-m-L-sarcolysyl-p-L-fluorophenylalanine ethyl ester): comparison with melphalan},
  author={J. Gullbo and S. Dhar and K. Luthman and H. Ehrsson and R. Lewensohn and P. Nygren and R. Larsson},
  journal={Anti-Cancer Drugs},
  year={2003},
  volume={14},
  pages={617-624}
}
Peptichemio, a mixture of six short oligopeptides all comprising the alkylating amino acid m-L-sarcolysin, has shown clinical activity in several malignancies. Previous studies have suggested that activity mainly resides in one of the peptides, P2 (L-prolyl-m-L-sarcolysyl-p-L-fluorophenylalanine ethyl ester). In the present study the in vitro activity of P2 was further investigated and compared to melphalan and the novel alkylating dipeptide J1 (L-melphalanyl-p-L-fluorophenylalanine ethyl ester… Expand
Antitumor activity of the novel melphalan containing tripeptide J3 (L-prolyl-L-melphalanyl-p-L-fluorophenylalanine ethyl ester): comparison with its m-L-sarcolysin analogue P2.
Peptichemio (PTC), a mixture of six oligopeptides all containing m-L-sarcolysin, has previously shown impressive results in clinical trials. The tripeptide P2Expand
The alkylating prodrug J1 can be activated by aminopeptidase N, leading to a possible target directed release of melphalan.
TLDR
A role of APN in the activation of the melphalan prodrug J1 and subsequently, its cytotoxic effects is demonstrated and data suggest that J1 may be activated in a tumor selective manner. Expand
Activity of Hydrolytic Enzymes in Tumour Cells is a Determinant for Anti-tumour Efficacy of the Melphalan Containing Prodrug J1
TLDR
The results show that the activity of the dipeptide mustards is highly dependent on intracellular hydrolysis, which result in rapid intrACEllular release of the alkylating unit in cells with high enzymatic activity. Expand
Antitumor efficacy and acute toxicity of the novel dipeptide melphalanyl-p-L-fluorophenylalanine ethyl ester (J1) in vivo
TLDR
The results indicate that the promising in vitro data from the previous studies of J1 seems translatable into the in vivo situation, and at equal doses of alkylating units J1 was more active in the mouse hollow-fiber model, but showed similar general toxicity. Expand
The novel alkylating prodrug melflufen (J1) inhibits angiogenesis in vitro and in vivo.
TLDR
This study demonstrates through all methods used, that melphalan-flufenamide besides being an alkylating agent also reveals anti-angiogenic effects in different preclinical models in vitro and in vivo. Expand
The novel melphalan prodrug J1 inhibits neuroblastoma growth in vitro and in vivo
TLDR
The melphalan prodrug J1 is highly active in models of neuroblastoma in vitro and in vivo, encouraging further clinical development in this patient group. Expand
Melflufen - a peptidase-potentiated alkylating agent in clinical trials.
TLDR
It is hypothesized that melflufen could provide better efficacy but no more toxicity than what is achieved with melphalan, an assumption so far supported by experiences from hollow fiber and xenograft studies in rodents as well as by clinical data from patients with solid tumors and multiple myeloma. Expand
The novel alkylating prodrug J1: diagnosis directed activity profile ex vivo and combination analyses in vitro
TLDR
The ex vivo profile of J 1 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. Expand
In vitro and in vivo activity of melflufen (J1)in lymphoma
TLDR
This study confirms previous reports of a targeting related potency superiority of melflufen compared to that of melphalan and appears to be a candidate for further evaluation in the treatment of this group of malignant diseases. Expand
In vitro and in vivo activity of melflufen ( J 1 ) in lymphoma
Background: Melphalan has been used in the treatment of various hematologic malignancies for almost 60 years. Today it is part of standard therapy for multiple myeloma and also as part ofExpand
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TLDR
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TLDR
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