Simply select your manager software from the list below and click on. 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. Side effects of alkeran melphalan, warnings, uses rxlist. Melphalan inhibits dna and rna synthesis via formation of interstrand cross links with dna, likely binding at the n. Melphalan is also available in an injectable form for patients who cannot take melphalan by mouth. 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. Toxicity estimation software tool test safer chemicals. Alkeran for injection is supplied as a sterile, nonpyrogenic, freezedried powder. Structure of vinblastinechemicallyit is a complex structure consisting of two polycyclic units i. Melphalan synthesis, sar, mcq and chemical structure. Melphalan injection, at high intravenous dosage, is indicated, with or without haematopoietic stem cell transplantation, for the. Alkeran melphalan tablets are indicated for the palliative treatment of multiple myeloma and for the palliation of nonresectable epithelial carcinoma of the ovary.
Our alkeran melphalan side effects drug center provides a comprehensive view of available drug information on the potential side effects when taking this medication. 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. This medicine is used to treat multiple myeloma and ovarian cancer. 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. This results can be explained due to the peg chain being attached to the drug.
Qsars are mathematical models used to predict measures of toxicity from the physical characteristics of the structure of chemicals known as molecular descriptors. The novel melphalan prodrug j1 inhibits neuroblastoma. In vitro and in vivo antitumor activity of a novel alkylating agent melphalanflufenamide against multiple myeloma cells. It is not known whether this drug is excreted in human milk. Melphalan is an orally available phenylalanine derivative of nitrogen mustard with antineoplastic activity.
Melphalan, sold under the trade name alkeran among others, is a chemotherapy medication used to treat multiple myeloma, ovarian cancer, melanoma, and amyloidosis. 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. Bivalent bendamustine and melphalan derivatives as. It is assumed that molecules having similar structure will have similar.
Structureactivity relationship for alkylating dipeptide nitrogen. In vitro and in vivo antitumor activity of a novel alkylating agent, melphalanflufenamide, against multiple myeloma cells. Definition from the nci drug dictionary detailed scientific definition and other names for. We evaluated the stability of melphalan solution after reconstitution of the commercial product and serial dilution with saline to a final concentration of 300. We need some basic information from you to serve you better. 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. In vitro and in vivo antitumor activity of a novel alkylating agent. The activity of j1 lmelphalanylplfluorophenylalanine ethyl ester, an enzymatically activated melphalan prodrug, was evaluated in neuroblastoma models in vitro and in vivo. Structureactivity relationships of linear and cyclic.
According to the manufacturer, melphalan is stable in sterile 0. 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. There is a relationship between molecular structures and their biological activity, and this principle is referred to as structure activity relationship sar. A, chemical structures of the melphalancontaining dipeptide. Neuroblastoma is the most common extracranial solid tumor of childhood. According to this structureactivity relationship sar study, chs 828. Melphalan is a phenylalanine derivative of nitrogen mustard with antineoplastic activity. Quantitative structureactivity relationship models qsar models are regression or. Structureactivity relationships of linear and cyclic peptides containing the. This concentration was chosen because in our practice we administer 0. The statistical analysis was undertaken using commercial software. 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. As discussed below, overall response rates at week 22 were comparable. If you have the appropriate software installed, you can download article citation data to the citation manager of your choice.
Common side effects include nausea and bone marrow suppression. The major difference is that melphalan is actively transported into tumor cells by amino acid transporters 7 and. Melphalan is a cancer medication that interferes with the growth and spread of cancer cells in the body. In order to increase their antitumor potency and tumor selectivity both compounds were integrated in structureactivity relationship studies. Along with their needed effects, medicines like melphalan can sometimes cause unwanted effects such as blood problems and other side effects. Bivalent bendamustine and melphalan derivatives as anticancer agents article in european journal of medicinal chemistry 465. Quantitative structurecytotoxicity relationship of 3ncyclicamino. Tumor volume and survival in mice was measured using the graphpad prism graphpad softwareversion. Stability of melphalan solution for intravitreal injection.
Melphalan is practically insoluble in water and has a pka. Can anyone suggest me some free online tools for quantitative. Finally, the in vivo toxicity and activity of melphalan and j3 were investigated in mice bearing human leukemia cells in s. If the target structure is known, computational chemistry and molecular modelling software packages can be useful in identifying binding site interactions. Melphalan is an alkylating agent that is a white to buff odorless powder at room temperature. Melphalan is a phenylalanine mustard that is available orally for treatment of multiple myeloma and carcinomas of the ovaries and breast. Sar tools like cdd vault can detect correlations and build models used to evaluate new chemical structures to predict their biological activity. Structureactivity relationship for alkylating dipeptide nitrogen mustard derivatives. In vitro and in vivo antitumor activity of a novel. The melphalan haemolytic activity was measured to 100% above the concentration 3. Melphalan lphenylalanine mustard is a nitrogen mustard containing dna crosslinking agent with a similar structure and pharmacology to chlorambucil.
Molecular modeliing, open source program library for molecular simulation applications. Structureactivity relationship for alkylating dipeptide. Two different three dimensional quantitative structural activity relationship 3dqsar studies, comparative. 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. To date, the melflufen activity against multiple myeloma cells is. Melphalan is an anticancer antineoplastic or cytotoxic chemotherapy drug. 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.
Insilico modelling of quantitative structureactivity relationship of. Melphalan definition of melphalan by the free dictionary. Over the last 60 years there have been a multitude of ways to capture structureactivity relationships. Severe bone marrow suppression with resulting infection or bleeding may occur. Melphalan is a bifunctional alkylating agent that is active against selected human neoplastic diseases. Melphalan is a chemotherapy medication fitting in with the class of nitrogen mustard. Such methodologies are unequivocally judgmental to give not just the solid forecast of particular properties of new analogs, but also illustrate.
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. The following data is based on the product molecular weight 305. Melphalan 50 mg powder and solvent for solution for. Quantitative structureactivity relationship wikipedia. We can broadly divide them into two groups those based on statistical or data mining methods e. The presence of acetyl group is very essential for vinblastine to exhibit itanti cancer activity. Structureactivity relationship in cultured murine l1210 leukemia cells. Melphalan should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. 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. Department of clinical haematology oxford bmt programme b. Find patient medical information for melphalan oral on webmd including its uses, side effects and safety, interactions, pictures, warnings and user ratings. Melphalan is an active cytotoxic agent for use only under the direction of physicians experienced in the administration of such agents. On the other hand the haemolytic activity of melphalan versus its conjugates was also determined by assessing the haemoglobin content.
A quantitative structureactivity relationship qsar study was carried out on 112. Melphalan injection, at conventional intravenous dosage, is indicated in the treatment of multiple myeloma and ovarian cancer. Several authors have studied the stability of different concentrations of melphalan. A randomized trial compared prednisone plus iv melphalan to prednisone plus oral melphalan in the treatment of myeloma. The proteasome inhibitor cep18770 enhances the anti. Chemical modification of melphalan as a key to improving. Melphalan is an alkylating agent frequently used in an intravenous formulation to treat hematologic malignancies and solid tumors in both adults and children.
For more information, see the drug information summary for melphalan hydrochloride. Melphalan, also known as lphenylalanine mustard, phenylalanine mustard, lpam, or lsarcolysin, is a phenylalanine derivative of nitrogen mustard. This is accomplished via transarterial catheter based slow pulsed infusion into the ophthalmic artery. Structureactivity relationship analysis of cytotoxic cyanoguanidines. Melphalan cytotoxicity to murine l1210 leukemia cells in culture was. Seven neuroblastoma cell lines with various levels of drug resistance were screened for cytotoxicity of j1 alone or in combination with. Melphalan, a bifunctional nitrogen mustardderivative alkylating agent, is the lisomer of mechlorethamine. Half the patients received six 28day cycles of melphalan 0. Surprisingly however, the melphalan containing tripeptide j3 demonstrated a significantly more rapid and stronger activity than the m lsarcolysin analogue p2. 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. Melphalan is used to treat multiple myeloma a type of. Alkeran should not be given to nursing mothers and has not been approved for use in pediatric populations. 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. Bivalent bendamustine and melphalan derivatives as anticancer.
Melphalan side effects, dosage, interactions drugs. Encapsulation of chemotherapeutic drug melphalan in. 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. Please which program used for determination the structure activity relationship sar for pharmaceutical compounds. Each singleuse vial contains melphalan hydrochloride equivalent to 50 mg melphalan and 20 mg povidone. Commonly used qsar assessment software such as derek or mcase is used to genotoxicity of impurity according to ich m7. Quantitative structureactivity relationship study on potent. As far as we know, the biological activity of 3aminochromones, structural. Alkeran for injection is reconstituted using the sterile diluent provided. 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. Cellcycle analysis was performed with cell sorter software version 2. Insilico modelling of quantitative structureactivity relationship of pgi50.
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