Alkeran for injection is supplied as a sterile, nonpyrogenic, freezedried powder. Melphalan is an alkylating agent that is a white to buff odorless powder at room temperature. Melphalan is an anticancer antineoplastic or cytotoxic chemotherapy drug. On the other hand the haemolytic activity of melphalan versus its conjugates was also determined by assessing the haemoglobin content. Insilico modelling of quantitative structureactivity relationship of pgi50. Tumor volume and survival in mice was measured using the graphpad prism graphpad softwareversion. Commonly used qsar assessment software such as derek or mcase is used to genotoxicity of impurity according to ich m7. This medication is classified as an alkylating agent.
The statistical analysis was undertaken using commercial software. The activity of j1 lmelphalanylplfluorophenylalanine ethyl ester, an enzymatically activated melphalan prodrug, was evaluated in neuroblastoma models in vitro and in vivo. Melphalan is a chemotherapy medication fitting in with the class of nitrogen mustard. Structureactivity relationship for alkylating dipeptide nitrogen. Melphalan inhibits dna and rna synthesis via formation of interstrand cross links with dna, likely binding at the n. Melphalan is a bifunctional alkylating agent that is active against selected human neoplastic diseases.
Stability of melphalan solution for intravitreal injection. Quantitative structureactivity relationship models qsar models are regression or. The major difference is that melphalan is actively transported into tumor cells by amino acid transporters 7 and. According to the manufacturer, melphalan is stable in sterile 0. Tnf administered to b16f1 tumorbearing mice are sufficient to increase the antitumor activity of melphalan and that 10 410 5 greater doses of tnf are necessary to achieve. The novel melphalan prodrug j1 inhibits neuroblastoma. In vitro and in vivo antitumor activity of a novel alkylating agent melphalanflufenamide against multiple myeloma cells. Melphalan 2 mg tablets summary of product characteristics smpc by aspen. A randomized trial compared prednisone plus iv melphalan to prednisone plus oral melphalan in the treatment of myeloma. Structureactivity relationships of linear and cyclic peptides containing the.
Neuroblastoma is the most common extracranial solid tumor of childhood. To date, the melflufen activity against multiple myeloma cells is. Find patient medical information for melphalan oral on webmd including its uses, side effects and safety, interactions, pictures, warnings and user ratings. Melphalan definition of melphalan by the free dictionary. Melphalan, a bifunctional nitrogen mustardderivative alkylating agent, is the lisomer of mechlorethamine. The proteasome inhibitor cep18770 enhances the antimyeloma activity of bortezomib and melphalan article in british journal of haematology 1484. Controlled trials comparing intravenous iv to oral melphalan. Antitumor activity of the novel melphalan containing. In some cases, health care professionals may use the trade name megace alkeran or other names lpam or lsarcolysin or phenylalanine mustard when referring to the generic drug name melphalan. Structure activity relationship sar is an approach to find qualitative relationships between chemical structure and their biological activity quantitative structure activity relationship qsar models are theoretical models that relate a. Severe bone marrow suppression with resulting infection or bleeding may occur. Melphalan is an alkylating agent frequently used in an intravenous formulation to treat hematologic malignancies and solid tumors in both adults and children. We can broadly divide them into two groups those based on statistical or data mining methods e.
Structure activity relationship studies suggested influence of enzymatic activation since peptide composition both selection of amino acid moieties and order had dramatic effects on the. Melphalan lphenylalanine mustard is a nitrogen mustard containing dna crosslinking agent with a similar structure and pharmacology to chlorambucil. Melphalan should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. The following data is based on the product molecular weight 305. Melphalan 50 mg powder and solvent for solution for. Melphalan synthesis, sar, mcq and chemical structure. This medicine is used to treat multiple myeloma and ovarian cancer. Please which program used for determination the structure activity relationship sar for pharmaceutical compounds. Quantitative structureactivity relationship wikipedia.
It is assumed that molecules having similar structure will have similar. Bivalent bendamustine and melphalan derivatives as anticancer agents article in european journal of medicinal chemistry 465. Can anyone suggest me some free online tools for quantitative. Common side effects include nausea and bone marrow suppression. Over the last 60 years there have been a multitude of ways to capture structureactivity relationships. Melphalan cytotoxicity to murine l1210 leukemia cells in culture was. Definition from the nci drug dictionary detailed scientific definition and other names for. Bivalent bendamustine and melphalan derivatives as anticancer. Cytotoxicity occurs in both dividing and nondividing tumors.
Melphalan is an orally available phenylalanine derivative of nitrogen mustard with antineoplastic activity. As discussed below, overall response rates at week 22 were comparable. Qsars are mathematical models used to predict measures of toxicity from the physical characteristics of the structure of chemicals known as molecular descriptors. Toxicity estimation software tool test safer chemicals.
A comprehensive approach to the structureantiproliferative activity relationship was proposed by attempting to compare the modification of both the carboxyl and amino groups of the parent molecule. Melphalan alkylates dna at the n7 position of guanine and induces dna interstrand crosslinkages, resulting in the inhibition of dna and rna synthesis and cytotoxicity against both dividing and nondividing tumor cells. Melphalan, sold under the trade name alkeran among others, is a chemotherapy medication used to treat multiple myeloma, ovarian cancer, melanoma, and amyloidosis. Seven neuroblastoma cell lines with various levels of drug resistance were screened for cytotoxicity of j1 alone or in combination with. It is not known whether this drug is excreted in human milk. Structureactivity relationship for alkylating dipeptide nitrogen mustard derivatives. The formation of inclusion complexes between drugs and macrocycles has proven to be an effective strategy to increase solubilization and stabilization of the drug, while in several cases improving their biological activity. Quantitative structural activity relationship qsar process quantitatively. Quantitative structureactivity relationship study on potent.
Melphalan injection, at high intravenous dosage, is indicated, with or without haematopoietic stem cell transplantation, for the. Melphalan is a phenylalanine mustard that is available orally for treatment of multiple myeloma and carcinomas of the ovaries and breast. Structureactivity relationship for alkylating dipeptide. Melphalan is used to treat multiple myeloma a type of. Cellcycle analysis was performed with cell sorter software version 2. Structure activity relationship sar analysis software programs, such as oncologic and multicase mcase, work by analyzing the chemical structure of a compound of unknown toxicity and predicting its likelihood to be a carcinogen based on comparisons to the structures of compounds with known toxicity and programmed chemical and. A quantitative structureactivity relationship qsar study was carried out on 112. Quantitative structureactivity relationship qsar study performs an urgent part in novel drug design and con. Also, because of the way these medicines act on the body, there is a chance that they might cause other unwanted effects that may not occur until months or years. Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions. If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Encapsulation of chemotherapeutic drug melphalan in. Melphalan is an active cytotoxic agent for use only under the direction of physicians experienced in the administration of such agents.
This results can be explained due to the peg chain being attached to the drug. Initially, pharmacophore modeling was carried out in molecular operating environment moe software to identify the interaction pharmacophore elements ipe and their relative geometry in threedimensional space. The melphalan haemolytic activity was measured to 100% above the concentration 3. In vitro and in vivo antitumor activity of a novel alkylating agent. Two different three dimensional quantitative structural activity relationship 3dqsar studies, comparative. Simply select your manager software from the list below and click on. There is a relationship between molecular structures and their biological activity, and this principle is referred to as structure activity relationship sar. Structureactivity relationship analysis of cytotoxic cyanoguanidines. If the target structure is known, computational chemistry and molecular modelling software packages can be useful in identifying binding site interactions. In vitro and in vivo antitumor activity of a novel. In order to increase their antitumor potency and tumor selectivity both compounds were integrated in structureactivity relationship studies. Finally, the in vivo toxicity and activity of melphalan and j3 were investigated in mice bearing human leukemia cells in s.
Along with their needed effects, medicines like melphalan can sometimes cause unwanted effects such as blood problems and other side effects. In vitro and in vivo antitumor activity of a novel alkylating agent, melphalanflufenamide, against multiple myeloma cells. Chemical modification of melphalan as a key to improving. Molecular modeliing, open source program library for molecular simulation applications. As far as we know, the biological activity of 3aminochromones, structural. This concentration was chosen because in our practice we administer 0. It is practically insoluble in water, insoluble in chloroform and ether, slightly soluble in methanol, and soluble in ethanol, propylene glycol, 2% carboxymethylcellulose, and alkaline. Structureactivity relationships sar explore the relationship between a molecules biological activity and the three dimensional structure of the molecule. Several authors have studied the stability of different concentrations of melphalan. Alkeran melphalan tablets are indicated for the palliative treatment of multiple myeloma and for the palliation of nonresectable epithelial carcinoma of the ovary. A, chemical structures of the melphalancontaining dipeptide.
Melphalan is also available in an injectable form for patients who cannot take melphalan by mouth. The presence of acetyl group is very essential for vinblastine to exhibit itanti cancer activity. Melphalan is practically insoluble in water and has a pka. Melphalan is a phenylalanine derivative of nitrogen mustard with antineoplastic activity. Structureactivity relationship in cultured murine l1210 leukemia cells. The proteasome inhibitor cep18770 enhances the anti. Sar tools like cdd vault can detect correlations and build models used to evaluate new chemical structures to predict their biological activity. In this context, we explored the formation of an inclusion complex between chemotherapeutic drug melphalan mel and cucurbit7uril cb7, and studied its effect on mel. Melphalan is currently being used to treat ocular retinoblastoma, a pediatric solid tumor. Alkeran should not be given to nursing mothers and has not been approved for use in pediatric populations. We evaluated the stability of melphalan solution after reconstitution of the commercial product and serial dilution with saline to a final concentration of 300. Such methodologies are unequivocally judgmental to give not just the solid forecast of particular properties of new analogs, but also illustrate. Alkeran for injection is reconstituted using the sterile diluent provided.
According to this structureactivity relationship sar study, chs 828. Our alkeran melphalan side effects drug center provides a comprehensive view of available drug information on the potential side effects when taking this medication. Department of clinical haematology oxford bmt programme b. The toxicity estimation software tool test was developed to allow users to easily estimate the toxicity of chemicals using quantitative structure activity relationships qsars methodologies. For more information, see the drug information summary for melphalan hydrochloride. Surprisingly however, the melphalan containing tripeptide j3 demonstrated a significantly more rapid and stronger activity than the m lsarcolysin analogue p2.
We need some basic information from you to serve you better. Half the patients received six 28day cycles of melphalan 0. Melphalan, also known as lphenylalanine mustard, phenylalanine mustard, lpam, or lsarcolysin, is a phenylalanine derivative of nitrogen mustard. Quantitative structurecytotoxicity relationship of 3ncyclicamino. Bivalent bendamustine and melphalan derivatives as. Insilico modelling of quantitative structureactivity relationship of. Melphalan is erratically absorbed from the gastrointestinal tract, and to overcome this pitfall, intravenous melphalan is utilized for the high doses prescribed for bone marrow transplant conditioning regimens. This is accomplished via transarterial catheter based slow pulsed infusion into the ophthalmic artery. Melphalan side effects, dosage, interactions drugs. Structureactivity relationships of linear and cyclic. Melphalan is a cancer medication that interferes with the growth and spread of cancer cells in the body. Side effects of alkeran melphalan, warnings, uses rxlist. Structure of vinblastinechemicallyit is a complex structure consisting of two polycyclic units i.
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