8057-25-8

Upstream product

• 75-21-8 oxirane 
• 68199-91-7 4-amino-N-benzoyl-DL-phenylalanine ethyl ester 
• 90102-87-7 methyl α-benzamido-4-phenylalaninate 
• 297734-00-0 4-(bis-(2-hydroxyethyl)amino)-L-phenylalanine 
• 1195524-16-3 4-amino-N,N-phthaloyl-D-phenylalanin-ethyl ester 
• 3223-07-2 melphalan hydrochloride 
• 189744-28-3 N-(tert-butyloxycarbonyl)-4-(bis(2-chloroethyl)amino)-L-phenylalanine ethyl ester 
• 189744-27-2 N-boc-L-3-(4-bis(hydroxyethyl)aminophenyl)alanine ethyl ester 
• 67630-01-7 (S)-3-(4-aminophenyl)-2-tert-butoxycarbonylamino-propionic acid ethyl ester 
• 1217651-06-3 N-(t-butyloxycarbonyl)-4-[bis(2-hydroxyethyl)amino]-L-phenylalanine methyl ester 
• 62978-52-3 melphalan methyl ester hydrochloride salt 
• 6335-21-3 diethyl 2-acetamido-2-(4-aminobenzyl)malonate 
• 6265-87-8 2-acetylamino-2-(4-nitrobenzyl)malonic acid diethyl ester 
• 83772-59-2 4-<4-benzylidene>-4'-N,N-dimethylaminoaniline 

Downstream Products

• 102881-57-2 4-{4-[bis-(2-chloro-ethyl)-amino]-benzylidene}-2-methyl-4H-oxazol-5-one 
• 26367-45-3 N-formylsarcolysine 

Relevant academic research and scientific papers

Aminopeptidase expression in multiple myeloma associates with disease progression and sensitivity to melflufen

Multiple myeloma (MM) is characterized by extensive immunoglobulin production leading to an excessive load on protein homeostasis in tumor cells. Aminopeptidases contribute to proteolysis by catalyzing the hydrolysis of amino acids from proteins or peptides and function downstream of the ubiquitin–proteasome pathway. Notably, aminopeptidases can be utilized in the delivery of antibody and peptide-conjugated drugs, such as melflufen, currently in clinical trials. We analyzed the expression of 39 aminopeptidase genes in MM samples from 122 patients treated at Finnish cancer centers and 892 patients from the CoMMpass database. Based on ranked abundance, LAP3, ERAP2, METAP2, TTP2, and DPP7 were highly expressed in MM. ERAP2, XPNPEP1, DPP3, RNPEP, and CTSV were differentially expressed between relapsed/refractory and newly diagnosed MM samples (p a substrate for aminopeptidases LAP3, LTA4H, RNPEP, and ANPEP. The sensitivity of MM cell lines to melflufen was reduced by aminopeptidase inhibitors. These results indicate critical roles of aminopeptidases in disease progression and the activity of melflufen in MM.

Release of Amino- or Carboxy-Containing Compounds Triggered by HOCl: Application for Imaging and Drug Design

The overproduction of HOCl is highly correlated with diseases such as atherosclerosis, rheumatoid arthritis, and cancer. Whilst acting as a marker of these diseases, HOCl might also be used as an activator of prodrugs or drug delivery systems for the treatment of the corresponding disease. In this work, a new platform of HOCl probes has been developed that integrates detection, imaging, and therapeutic functions. The probes can detect HOCl, using both NIR emission and the naked eye in vitro, with high sensitivity and selectivity at ultralow concentrations (the detection limit is at the nanomolar level). Basal levels of HOCl can be imaged in HL-60 cells without special stimulation. Moreover, the probes provided by this platform can rapidly release either amino- or carboxy-containing compounds from prodrugs, during HOCl detection and imaging, to realize a therapeutic effect.

An Improved Process for the Synthesis of Melphalan and the Hydrochloride Salt

The present invention relates to an improved process for the preparation of Melphalan, more specifically the invention relates to an efficient process for the preparation of substantially pure Melphalan hydrochloride (I).

PROCESS FOR THE PURIFICATION OF MELPHALAN

A method for the purification and preparation of melphalan that allows to obtain melphalan with purity higher than 99.5% is described.

PROCESS FOR THE PREPARATION OF MELPHALAN HYDROCHLORIDE

The present invention provides a simple and efficient method for synthesis of 4-[bis (2-chloroethyl)-amino]-L-phenylalanine hydrochloride. The process involves the treatment of 4-[bis(2-chloroethyl)-amino]-L-phenylalanine free base with hydrochloric acid in water followed by isolation of 4-[bis(2-chloroethyl)-amino]-phenylalanine hydrochloride of desired purity.

THERAPEUTIC FOR HEPATIC CANCER

A novel pharmaceutical composition for treating or preventing hepatocellular carcinoma and a method of treatment are provided. A pharmaceutical composition for treating or preventing liver cancer is obtained by combining a chemotherapeutic agent with an anti-glypican 3 antibody. Also disclosed is a pharmaceutical composition for treating or preventing liver cancer which comprises as an active ingredient an anti-glypican 3 antibody for use in combination with a chemotherapeutic agent, or which comprises as an active ingredient a chemotherapeutic agent for use in combination with an anti-glypican 3 antibody. Using the chemotherapeutic agent and the anti-glypican 3 antibody in combination yields better therapeutic effects than using the chemotherapeutic agent alone, and mitigates side effects that arise from liver cancer treatment with the chemotherapeutic agent.

SPECIFIC BINDING PROTEINS AND USES THEREOF

The present invention relates to specific binding members, particularly antibodies and fragments thereof, which bind to amplified epidermal growth factor receptor (EGFR) and to the de2-7 EGFR truncation of the EGFR. In particular, the epitope recognized by the specific binding members, particularly antibodies and fragments thereof, is enhanced or evident upon aberrant post-translational modification. These specific binding members are useful in the diagnosis and treatment of cancer. The binding members of the present invention may also be used in therapy in combination with chemotherapeutics or anti-cancer agents and/or with other antibodies or fragments thereof.

Anti-Claudin 3 Monoclonal Antibody and Treatment and Diagnosis of Cancer Using the Same

Monoclonal antibodies that bind specifically to Claudin 3 expressed on cell surface are provided. The antibodies of the present invention are useful for diagnosis of cancers that have enhanced expression of Claudin 3, such as ovarian cancer, prostate cancer, breast cancer, uterine cancer, liver cancer, lung cancer, pancreatic cancer, stomach cancer, bladder cancer, and colon cancer. The present invention provides monoclonal antibodies showing cytotoxic effects against cells of these cancers. Methods for inducing cell injury in Claudin 3-expressing cells and methods for suppressing proliferation of Claudin 3-expressing cells by contacting Claudin 3-expressing cells with a Claudin 3-binding antibody are disclosed. The present application also discloses methods for diagnosis or treatment of cancers.

Process Of Making Optically Pure Melphalan

This invention provides a process of making 4-(bis-(2-hydroxyethyl)amino)-L-phenylalanine of the formula by hydroxyethylation, in a regioselective manner, of the aromatic amino group rather than the glycinic amino group.

Pharmaceutical formulations

The present invention relates to a new two-component pharmaceutical formulation of melphalan in which the two components comprise (a) freeze-dried mephalan hydrochloride and (b) a solvent-diluent comprising a citrate, propylene glycol and ethanol. Substantially pure melphalan, substantially pure melphalan hydrochloride and methods for preparing them are also described.