89637-85-4

Basic information

• Product Name: N-^ε-10-methylpteroyl)-L-γ-glutamyl>-L-lysine
• CAS NO: 89637-85-4
• Molecular Weight: 582.619
• Mol File: 89637-85-4.mol
• Article Data: 1

Chemical Properties

• CAS DataBase Reference: N-^ε-10-methylpteroyl)-L-γ-glutamyl>-L-lysine(CAS DataBase Reference)
• NIST Chemistry Reference: N-^ε-10-methylpteroyl)-L-γ-glutamyl>-L-lysine(89637-85-4)
• EPA Substance Registry System: N-^ε-10-methylpteroyl)-L-γ-glutamyl>-L-lysine(89637-85-4)

Safety Data

• Hazardous Substances Data: 89637-85-4(Hazardous Substances Data)

Upstream product

• 89637-90-1 N-^α-(tert-butyloxycarbonyl)-N-^ε-10-methylpteroyl)-L-γ-glutamyl>-L-lysine tert-butyl(α-Glu)methyl(Lys) ester 
• 99532-86-2 N,2-[(1,1-dimethylethoxy)carbonyl]-L-lysine methyl ester hydrochloride 
• 79640-70-3 (S)-5-(tert-butoxy)-4-(4-(((2,4-diaminopteridin-6-yl)methyl)(methyl)amino)benzamido)-5-oxopentanoic acid 
• 89637-95-6 N-^α-(tert-butyloxycarbonyl)-N-^ε-10-methylpteroyl)-L-γ-glutamyl>-L-lysine tert-butyl(α-Glu) ester 

Relevant articles and documents

Methotrexate Analogues. 23. Synthesis, Dihydrofolate Reductase Affinity, Cytotoxicity, and in Vivo Antitumor Activity of Some Putative Degradation Products of Methotrexate-Poly(L-lysine) Conjugates

Derivatives of methotrexate (MTX) in which the γ-carbonyl group is joined to the ε-amino group of L-lysine, L-lysyl-L-lysine, or L-lysyl-L-lysyl-L-lysine, respectively, were prepared for evaluation of their dihydrofolate reductase (DHFR) affinity, their ability to retard cell growth in culture, and their antitumor activity in vivo.These small lysine derivatives of MTX are of interest as putative breakdown products of MTX-poly(L-lysine).Inhibition of DHFR in a cell-free assay was decreased only 3-fold relative to MTX, indicating that γ-substitution by up to three lysines is well tolerated for binding.On the other hand, toxicity toward L1210 murine leukemia cells in culture decreased up to 120-fold relative to MTX as the lysines increased in number from one to three, suggesting that uptake across the cell membrane becomes difficult when positively charged lysines are at the γ-position.Growth inhibition of H35 rat hepatoma cells was decreased 40- to 60-fold relative to MTX, but in H35R0.3 cells, which have normal DHFR content but are 180-fold MTX resistant by virtue of a transport defect, the lysine derivatives were only 3- to 7-fold less toxic than MTX.When the adducts were given to L1210 leukemic mice by twice-daily injection for 10 days an increase in life span (ILS) of 80-100percent was observed at 40 mg/kg (equivalent to 20-30 mg/kg of MTX).MTX itself, on the same schedule, gave a 100percent ILS at 0.5 mg/kg.The low in vivo activity of the mono-, di-, and trilysine adducts suggests minimal systemic hydrolysis to free MTX.