79648-88-7

Upstream product

• 19741-14-1 4-[(2,4-diaminopteridin-6-ylmethyl)methylamino]benzoic acid 
• 34582-33-7 α-tert-butyl-γ-methyl L-Glu diester hydrochloride 
• 1499-55-4 L-glutamic acid 5-methyl ester 
• 10541-83-0 N-methyl-p-aminobenzoic acid 
• 945-24-4 2,4-diamino-6-(hydroxymethyl)pteridine 
• 367275-86-3 1,1-dimethylethyl 5-methyl N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-glutamate 
• 84793-07-7 Fmoc-Glu-OtBu 
• 2528-30-5 4-<<(benzyloxy)carbonyl>methylamino>benzoic acid 
• 79640-72-5 L-glutamic acid 1-tert-butyl ester 5-methyl ester 
• 59368-16-0 6-bromomethyl-pteridine-2,4-diamine 
• 472960-79-5 2-(4-methylamino-benzoylamino)-pentanedioic acid 1-tert-butyl ester 5-methyl ester 

Downstream Products

• 940952-00-1 C₃₀H₄₀N₈O₇ 
• 181040-33-5 N^α-[[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-(α-tert-butoxy)glutamoyl]-N-[2-[(1-oxohexadecyl)oxy]-1,1-bis[[(1-oxohexadecyl)oxy]methyl]ethyl]glycinamide 
• 181040-49-3 N^α-[[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-(α-tert-butoxy)glutamoyl]-N-[1-hydroxymethyl-2-[(1-oxohexadecyl)oxy]-1-[(1-oxohexadecyl)oxymethyl]ethyl]glycinamide 
• 511544-99-3 N^α-[[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-(α-tert-butoxy)glutamoyl]-N-[1,1-bis(hydroxymethyl)-2-[(1-oxohexadecyl)oxy]ethyl]glycinamide 
• 181040-47-1 N^α-[[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-(α-tert-butoxy)glutamoyl]-N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]glycinamide 
• 79640-69-0 tert-butyl N'-<4--N-methylamino>benzoyl>-L-glutamic acid γ-hydrazide 

Relevant academic research and scientific papers

Synthesis of methotrexate-containing heterodimeric molecules

The present invention relates to novel compositions of methotrexate-containing heterodimeric probe molecules, also known as chemical inducers of dimerization (CID), useful in three-hybrid assays. The invention further relates to synthesis of said compositions and their intermediates. Another aspect of the invention is a method for using the heterodimeric probe molecules described herein in drug screens to identify potential protein targets to a given ligand, optimize protein-ligand interactions, or identify potential ligands for a given protein target. In certain embodiments, the invention contemplates the synthesis of the following methotrexate-containing heterodimeric probe:

Synthesis, cleavage profile, and antitumor efficacy of an albumin-binding prodrug of methotrexate that is cleaved by plasmin and cathepsin B

Cathepsin B and plasmin are intra- or extracellular proteases that are overexpressed by several solid tumors. In order to exploit both proteases as molecular targets for tumor-specific cleavage of prodrugs, an albumin-binding formulation of methotrexate w

Tight binding ligand approach to oligosaccharide-grafted protein

A novel type of artificial glycoprotein was developed, by using dihydrofolate reductase (DHFR) and methotrexate (MTX) as a protein-ligand pair. Various oligosaccharides linked to MTX were shown to bind tightly with DHFR and afforded oligosaccharide-grafted protein, which could be isolated easily by lectin beads.

The use of Tris-lipidation to modify drug cytotoxicity in multidrug resistant cells expressing P-glycoprotein or MRP1

1. Increasing the lipophilicity is a strategy often used to improve a compound's cellular uptake and retention but this may also convert it into a substrate for an ATP-dependent transporter such as P-glycoprotein or the multidrug resistance-associated pro

Synthesis of methotrexate-antibody conjugates by regiospecific coupling and assessment of drug and antitumor activities

In order to increase the retention of drug activity, regiospecific coupling has been used to synthesize conjugates of methotrexate (MTX, 1) with normal rabbit IgG (NRG) and a mouse anti-human renal cancer monoclonal IgG (Dal K-20). MTX γ-methyl ester (4) was produced either by selective esterification of MTX or by coupling of 4-amino-4-deoxy-N10-methylpteroic acid (2) with suitable glutamic acid derivatives. The MTX γ-methyl ester (4) was then converted to the corresponding hydrazide 6. An amide-linked conjugate was formed when the MTX γ-hydrazide (6) was converted to reactive acylating species 7 by using tert-butyl nitrite or trifluoroacetaldehyde, which were reacted with nucleophilic centers, presumably ε-amino groups, in native IgG. A hydrazone-linked conjugate was formed when MTX γ-hydrazide (6) was reacted directly with IgG that had first been oxidized with periodate to form polyaldehyde IgG. The regiospecifically synthesized conjugates were somewhat more effective inhibitors in vitro of dihydrofolate reductase and of colony formation by human renal cancer (Caki-1) cells than were control nonregiospecific conjugates.

Methotrexate Analogues. 14. Synthesis of New γ-Substituted Derivatives as Dihydrofolate Reductase Inhibitors and Potential Anticancer Agents

The γ-tert-butyl ester (1), γ-hydrazide (2), γ-n-butylamide (3), and γ-benzylamide (4) derivatives of methotrexate (MTX) were synthesized from 4-amino-4-deoxy-N10-methylpteroic acid (APA) and the appropriate blocked L-glutamic acid precursors with the aid of the peptide bond forming reagent diethyl phosphorocyanidate.The affinity of these side chain modified products for dihydrofolate reductase (DHFR) from Lactobacillus casei and L1210 mouse leukemic cells was determined spectrophotometrically or by competitive radioligand binding assay, and their cytotoxicity was evaluated against L1210 leukemic cells in culture.The results provide continuing support for the view that the "γ-terminal region" of the MTX side chain is an attractive site for molecular modification of this anticancer agent.