Carrier- and receptor-mediated transport of folate antagonists targeting folate-dependent enzymes: correlates of molecular-structure and biological activity.

@article{Westerhof1995CarrierAR,
  title={Carrier- and receptor-mediated transport of folate antagonists targeting folate-dependent enzymes: correlates of molecular-structure and biological activity.},
  author={G. Robbin Westerhof and Jan H. Schornagel and Ietje Kathmann and Ann L. Jackman and Andre Rosowsky and Ronald A Forsch and John B. Hynes and Frederick Boyle and Godefridus J. Peters and Herbert M. Pinedo},
  journal={Molecular pharmacology},
  year={1995},
  volume={48 3},
  pages={459-71}
}
The transport properties and growth-inhibitory potential of 37 classic and novel antifolate compounds have been tested in vitro against human and murine cell lines expressing different levels of the reduced folate carrier (RFC), the membrane-associated folate binding protein (mFBP), or both. The intracellular targets of these drugs were dihydrofolate reductase (DHFR), glycinamide ribonucleotide transformylase (GARTF), folylpolyglutamate synthetase (FPGS), and thymidylate synthase (TS… CONTINUE READING
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Substitutions at the 2-position ( e.g. , 2-CH3 ) improved the RFC substrate affinity for methotrexate and aminopterin .
Methotrexate , aminopterin , N10-propargyl-5,8-dideazafolic acid ( CB3717 ) , ZD1694 , 5,8-dideazaisofolic acid ( IAHQ ) , 5,10-dideazatetrahydrofolic acid ( DDATHF ) , and 5-deazafolic acid ( efficient substrate for FPGS ) were used as the basic structures in the present study , from which modifications were introduced in the pteridine / quinazoline ring , the C9-N10 bridge , the benzoyl ring , and the glutamate side chain .
Methotrexate , aminopterin , N10-propargyl-5,8-dideazafolic acid ( CB3717 ) , ZD1694 , 5,8-dideazaisofolic acid ( IAHQ ) , 5,10-dideazatetrahydrofolic acid ( DDATHF ) , and 5-deazafolic acid ( efficient substrate for FPGS ) were used as the basic structures in the present study , from which modifications were introduced in the pteridine / quinazoline ring , the C9-N10 bridge , the benzoyl ring , and the glutamate side chain .
Substitutions at the 2-position ( e.g. , 2-CH3 ) improved the RFC substrate affinity for methotrexate and aminopterin .
Methotrexate , aminopterin , N10-propargyl-5,8-dideazafolic acid ( CB3717 ) , ZD1694 , 5,8-dideazaisofolic acid ( IAHQ ) , 5,10-dideazatetrahydrofolic acid ( DDATHF ) , and 5-deazafolic acid ( efficient substrate for FPGS ) were used as the basic structures in the present study , from which modifications were introduced in the pteridine / quinazoline ring , the C9-N10 bridge , the benzoyl ring , and the glutamate side chain .
Methotrexate , aminopterin , N10-propargyl-5,8-dideazafolic acid ( CB3717 ) , ZD1694 , 5,8-dideazaisofolic acid ( IAHQ ) , 5,10-dideazatetrahydrofolic acid ( DDATHF ) , and 5-deazafolic acid ( efficient substrate for FPGS ) were used as the basic structures in the present study , from which modifications were introduced in the pteridine / quinazoline ring , the C9-N10 bridge , the benzoyl ring , and the glutamate side chain .
Substitutions at the 2-position ( e.g. , 2-CH3 ) improved the RFC substrate affinity for methotrexate and aminopterin .
Methotrexate , aminopterin , N10-propargyl-5,8-dideazafolic acid ( CB3717 ) , ZD1694 , 5,8-dideazaisofolic acid ( IAHQ ) , 5,10-dideazatetrahydrofolic acid ( DDATHF ) , and 5-deazafolic acid ( efficient substrate for FPGS ) were used as the basic structures in the present study , from which modifications were introduced in the pteridine / quinazoline ring , the C9-N10 bridge , the benzoyl ring , and the glutamate side chain .
Methotrexate , aminopterin , N10-propargyl-5,8-dideazafolic acid ( CB3717 ) , ZD1694 , 5,8-dideazaisofolic acid ( IAHQ ) , 5,10-dideazatetrahydrofolic acid ( DDATHF ) , and 5-deazafolic acid ( efficient substrate for FPGS ) were used as the basic structures in the present study , from which modifications were introduced in the pteridine / quinazoline ring , the C9-N10 bridge , the benzoyl ring , and the glutamate side chain .
Methotrexate , aminopterin , N10-propargyl-5,8-dideazafolic acid ( CB3717 ) , ZD1694 , 5,8-dideazaisofolic acid ( IAHQ ) , 5,10-dideazatetrahydrofolic acid ( DDATHF ) , and 5-deazafolic acid ( efficient substrate for FPGS ) were used as the basic structures in the present study , from which modifications were introduced in the pteridine / quinazoline ring , the C9-N10 bridge , the benzoyl ring , and the glutamate side chain .
Methotrexate , aminopterin , N10-propargyl-5,8-dideazafolic acid ( CB3717 ) , ZD1694 , 5,8-dideazaisofolic acid ( IAHQ ) , 5,10-dideazatetrahydrofolic acid ( DDATHF ) , and 5-deazafolic acid ( efficient substrate for FPGS ) were used as the basic structures in the present study , from which modifications were introduced in the pteridine / quinazoline ring , the C9-N10 bridge , the benzoyl ring , and the glutamate side chain .
Methotrexate , aminopterin , N10-propargyl-5,8-dideazafolic acid ( CB3717 ) , ZD1694 , 5,8-dideazaisofolic acid ( IAHQ ) , 5,10-dideazatetrahydrofolic acid ( DDATHF ) , and 5-deazafolic acid ( efficient substrate for FPGS ) were used as the basic structures in the present study , from which modifications were introduced in the pteridine / quinazoline ring , the C9-N10 bridge , the benzoyl ring , and the glutamate side chain .
Methotrexate , aminopterin , N10-propargyl-5,8-dideazafolic acid ( CB3717 ) , ZD1694 , 5,8-dideazaisofolic acid ( IAHQ ) , 5,10-dideazatetrahydrofolic acid ( DDATHF ) , and 5-deazafolic acid ( efficient substrate for FPGS ) were used as the basic structures in the present study , from which modifications were introduced in the pteridine / quinazoline ring , the C9-N10 bridge , the benzoyl ring , and the glutamate side chain .
Methotrexate , aminopterin , N10-propargyl-5,8-dideazafolic acid ( CB3717 ) , ZD1694 , 5,8-dideazaisofolic acid ( IAHQ ) , 5,10-dideazatetrahydrofolic acid ( DDATHF ) , and 5-deazafolic acid ( efficient substrate for FPGS ) were used as the basic structures in the present study , from which modifications were introduced in the pteridine / quinazoline ring , the C9-N10 bridge , the benzoyl ring , and the glutamate side chain .
Methotrexate , aminopterin , N10-propargyl-5,8-dideazafolic acid ( CB3717 ) , ZD1694 , 5,8-dideazaisofolic acid ( IAHQ ) , 5,10-dideazatetrahydrofolic acid ( DDATHF ) , and 5-deazafolic acid ( efficient substrate for FPGS ) were used as the basic structures in the present study , from which modifications were introduced in the pteridine / quinazoline ring , the C9-N10 bridge , the benzoyl ring , and the glutamate side chain .
The intracellular targets of these drugs were dihydrofolate reductase ( DHFR ) , glycinamide ribonucleotide transformylase ( GARTF ) , folylpolyglutamate synthetase ( FPGS ) , and thymidylate synthase ( TS ) .
Neoplastic CellIs abnormal cell of diseaseNeoplasms
Given the fact that for an increasing number of normal and neoplastic cells and tissue , different expression levels of RFC and mFBP are being recognized , this folate antagonist structure - activity relationship can be of value for predicting drug sensitivity and resistance of tumor cells or drug - related toxicity to normal cells and for the rational design and development of novel antifolates .
The intracellular targets of these drugs were dihydrofolate reductase ( DHFR ) , glycinamide ribonucleotide transformylase ( GARTF ) , folylpolyglutamate synthetase ( FPGS ) , and thymidylate synthase ( TS ) .
The intracellular targets of these drugs were dihydrofolate reductase ( DHFR ) , glycinamide ribonucleotide transformylase ( GARTF ) , folylpolyglutamate synthetase ( FPGS ) , and thymidylate synthase ( TS ) .
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