Synthesis and potent antifolate activity and cytotoxicity of B-ring deaza analogues of the nonpolyglutamatable dihydrofolate reductase inhibitor Nalpha-(4-amino-4-deoxypteroyl)-Ndelta-hemiphthaloyl- L-ornithine (PT523).

No abstract is available for this paper.

• Publication year

  1998

• Venue

  Journal of Medicinal Chemistry

• Publication date

  Unknown publication date

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1021/jm980477PMID 9857098
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Reduced folate carrier gene (RFC1) expression and anti‐folate resistance in transfected and non‐selected cell lines

  1997cited by this paper
• Comparison of two independent crystal structures of human dihydrofolate reductase ternary complexes reduced with nicotinamide adenine dinucleotide phosphate and the very tight-binding inhibitor PT523.

  1997cited by this paper
• Differences in folylpolyglutamate synthetase and dihydrofolate reductase expression in human B-lineage versus T-lineage leukemic lymphoblasts: mechanisms for lineage differences in methotrexate polyglutamylation and cytotoxicity.

  1997cited by this paper
• Characterization of the p53 tumor suppressor pathway in cell lines of the National Cancer Institute anticancer drug screen and correlations with the growth-inhibitory potency of 123 anticancer agents.

  1997cited by this paper
• NMR solution structure of the antitumor compound PT523 and NADPH in the ternary complex with human dihydrofolate reductase.

  1997cited by this paper
• Preventive effect of a novel antifolate, MX-68, in murine systemic lupus erythematosus (SLE).

  1997cited by this paper
• Synthesis and evaluation of novel fluorinated methotrexate derivatives for application to rheumatoid arthritis treatment.

  1997cited by this paper
• Antirheumatic agents: novel methotrexate derivatives bearing a benzoxazine or benzothiazine moiety.

  1997cited by this paper
• Analogues of N alpha-(4-amino-4-deoxypteroyl)-N delta-hemiphthaloyl-L-ornithine (PT523) modified in the side chain: synthesis and biological evaluation.

  1997cited by this paper
• Carrier- and receptor-mediated transport of folate antagonists targeting folate-dependent enzymes: correlates of molecular-structure and biological activity.

  1995cited by this paper
• Dihydrofolate reductase binding and cellular uptake of nonpolyglutamatable antifolates: correlates of cytotoxicity toward methotrexate-sensitive and -resistant human head and neck squamous carcinoma cells.

  1995cited by this paper
• 2,4-Diaminopyrido[3,2-d]pyrimidine inhibitors of dihydrofolate reductase from Pneumocystis carinii and Toxoplasma gondii.

  1995cited by this paper
• Synthesis and biological activity of N omega-hemiphthaloyl-alpha,omega- diaminoalkanoic acid analogues of aminopterin and 3',5-dichloroaminopterin.

  1994cited by this paper
• Biochemical studies on PT523, a potent nonpolyglutamatable antifolate, in cultured cells.

  1994cited by this paper
• Differences in constitutive and post-methotrexate folylpolyglutamate synthetase activity in B-lineage and T-lineage leukemia.

  1994cited by this paper
• Intrinsic resistance of cervical squamous cell carcinoma cell lines to methotrexate (MTX) as a result of decreased accumulation of intracellular MTX polyglutamates.

  1993cited by this paper
• In vitro activity of novel antifolates against human squamous carcinoma cell lines of the head and neck with inherent resistance to methotrexate

  1992cited by this paper
• Synthesis and antifolate evaluation of the 10-propargyl derivatives of 5-deazafolic acid, 5-deazaaminopterin, and 5-methyl-5-deazaaminopterin.

  1992cited by this paper
• Intrinsic resistance to methotrexate in human soft tissue sarcoma cell lines.

  1992cited by this paper
• Morphological and immunocytochemical characteristics of human tumor cell lines for use in a disease-oriented anticancer drug screen.

  1992cited by this paper
• Multidrug-resistant phenotype of disease-oriented panels of human tumor cell lines used for anticancer drug screening.

  1992cited by this paper
• Synthesis and in vitro biological activity of new deaza analogues of folic acid, aminopterin, and methotrexate with an L-ornithine side chain.

  1991cited by this paper
• Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines.

  1991cited by this paper
• Basis for natural resistance to methotrexate in human acute non-lymphocytic leukemia.

  1991cited by this paper
• In vitro metabolism of 5,8-dideazafolates and 5,8-dideazaisofolates by mammalian folylpoly-gamma-glutamate synthetase.

  1991cited by this paper
• Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts at diagnosis of childhood acute lymphoblastic leukemia: a pilot prognostic factor analysis.

  1990cited by this paper
• Inherent resistance of human squamous carcinoma cell lines to methotrexate as a result of decreased polyglutamylation of this drug.

  1989cited by this paper
• Cross-resistance to the lipid-soluble antifolate trimetrexate in human carcinoma cells with the multidrug-resistant phenotype.

  1989cited by this paper
• Cytotoxicity, uptake, polyglutamate formation, and antileukemic effects of 8-deaza analogues of methotrexate and aminopterin in mice.

  1988cited by this paper
• Kinetics of the formation and isomerization of methotrexate complexes of recombinant human dihydrofolate reductase.

  1988cited by this paper
• Expression and site-directed mutagenesis of human dihydrofolate reductase.

  1988cited by this paper
• Structural design, biochemical properties, and evidence for improved therapeutic activity of 5-alkyl derivatives of 5-deazaaminopterin and 5-deazamethotrexate compared to methotrexate in murine tumor models.

  1988cited by this paper
• Mechanism of acquired resistance to methotrexate in P388 murine leukemia cells and in their doxorubicin-resistant subline.

  1988cited by this paper
• Syntheses and antifolate activity of 5-methyl-5-deaza analogues of aminopterin, methotrexate, folic acid, and N10-methylfolic acid.

  1986cited by this paper
• Cross resistance of pleiotropically drug resistant P338 leukemia cells to the lipophilic antifolates trimetrexate and BW 301U.

  1986cited by this paper
• Inhibition of phosphoribosylaminoimidazolecarboxamide transformylase by methotrexate and dihydrofolic acid polyglutamates.

  1985cited by this paper
• Enhanced inhibition of thymidylate synthase by methotrexate polyglutamates.

  1985cited by this paper
• Methotrexate analogues. 25. Chemical and biological studies on the gamma-tert-butyl esters of methotrexate and aminopterin.

  1985cited by this paper
• Inhibition of dihydrofolate reductase, methotrexate transport, and growth of methotrexate-sensitive and -resistant L1210 leukemia cells in vitro by 5-substituted 2,4-diaminoquinazolines.

  1985cited by this paper
• Methotrexate analogues. 20. Replacement of glutamate by longer-chain amino diacids: effects on dihydrofolate reductase inhibition, cytotoxicity, and in vivo antitumor activity.

  1983cited by this paper
• Intrinsic resistance to methotrexate of cultured mammalian cells in relation to the inhibition kinetics of their dihydrololate reductases.

  1976cited by this paper
• A linear equation that describes the steady-state kinetics of enzymes and subcellular particles interacting with tightly bound inhibitors.

  1972cited by this paper
• Quinazoline analogues of folic acid.

  1970cited by this paper

• Non-uniformity in in vitro drug-induced cytotoxicity as evidenced by differences in IC50 values - implications and way forward.

  2022cites this paper
• Methotrexate analogues display enhanced inhibition of TNF-α production in whole blood from RA patients

  2014influential citation
• Inhibition of the Proton-Coupled Folate Transporter (PCFT-SLC46A1) by Bicarbonate and Other Anions

  2013cites this paper
• Folate and thiamine transporters mediated by facilitative carriers (SLC19A1-3 and SLC46A1) and folate receptors.

  2013cites this paper
• Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance.

  2012cites this paper
• Treatment of Acute Lymphoblastic Leukaemia

  2012cites this paper
• Synthesis of highly functionalized 2,4-diaminoquinazolines as anticancer and anti-HIV agents.

  2010cites this paper
• Folate receptor beta as a potential delivery route for novel folate antagonists to macrophages in the synovial tissue of rheumatoid arthritis patients.

  2009cites this paper
• Recent advances in classical and non-classical antifolates as antitumor and antiopportunistic infection agents: Part II.

  2008cites this paper
• Targeting DMARD resistance in Rheumatoid Arthritis

  2008cites this paper
• Ultrafast de novo docking combining pharmacophores and combinatorics

  2007cites this paper
• Coexistence of multiple mechanisms of PT523 resistance in human leukemia cells harboring 3 reduced folate carrier alleles: transcriptional silencing, inactivating mutations, and allele loss.

  2006cites this paper
• Computer modelling of antifolate inhibition of folate metabolism using hybrid functional petri nets.

  2006cites this paper
• inactivating mutations and allele loss leukemia cells harboring three reduced folate carrier alleles : Coexistence of multiple mechanisms of PT 523-resistance in human

  2005cites this paper
• DNA and RNA synthesis: antifolates.

  2005cites this paper
• Synthesis and in vitro antifolate activity of rotationally restricted aminopterin and methotrexate analogues.

  2004cites this paper
• Susceptibility of human herpesvirus 8 as well as other herpesviruses and their enzymes towards various chemotherapeutical agents

  2004cites this paper
• Further studies on the interaction of nonpolyglutamatable aminopterin analogs with dihydrofolate reductase and the reduced folate carrier as determinants of in vitro antitumor activity.

  2003cites this paper
• Resistance to antifolates

  2003cites this paper
• Synthesis and in vitro antitumor activity of new deaza analogues of the nonpolyglutamatable antifolate N(alpha)-(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L-ornithine (PT523).

  2002cites this paper
• Gammaherpesviruses encode functional dihydrofolate reductase activity.

  2002cites this paper
• Synthesis of a novel phosphatidylcholine conjugated to docosahexaenoic acid and methotrexate that inhibits cell proliferation

  2002cites this paper
• Synthesis and enzymatic activation of N-[N(alpha)-(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L-ornithiny]-L-phenylalanine, a candidate for antibody-directed enzyme prodrug therapy (ADEPT).

  2002cites this paper
• Molecular, biochemical, and cellular pharmacology of pemetrexed.

  2002cites this paper
• Synthesis and antifolate evaluation of the aminopterin analogue with a bicyclo.

  2001cites this paper
• Marked suppression of the activity of some, but not all, antifolate compounds by augmentation of folate cofactor pools within tumor cells.

  2001cites this paper
• Interaction Energy Analyses of Folate Analog Binding to Human Dihydrofolate Reductase: Contribution of the Antifolate Substructural Regions to Complex Stability

  2000cites this paper
• Efficient utilization of the reduced folate carrier in CCRF-CEM human leukemic lymphoblasts by the potent antifolate N(alpha)-(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L- ornithine (PT523) and its B-ring analogues.

  2000cites this paper
• Analogues of the potent nonpolyglutamatable antifolate N(alpha)-(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L-ornithine (PT523) with modifications in the side chain, p-aminobenzoyl moiety, or 9,10-bridge: synthesis and in vitro antitumor activity.

  2000cites this paper
• The effect of side-chain, para-aminobenzoyl region, and B-ring modifications on dihydrofolate reductase binding, influx via the reduced folate carrier, and cytotoxicity of the potent nonpolyglutamatable antifolate N(alpha)-(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L- ornithine.

  2000cites this paper
• PT523 and other aminopterin analogs with a hemiphthaloyl-L-ornithine side chain: exceptionally tight-binding inhibitors of dihydrofolate reductase which are transported by the reduced folate carrier but cannot form polyglutamates.

  1999cites this paper