A novel antifolate suppresses growth of FPGS-deficient cells and overcomes methotrexate resistance

Mechanistic characterization of a novel, lipophilic antifolate that suppresses growth of FPGS-deficient cells that are linked to methotrexate resistance and relapse in cancer patients.

[1]  I. Ulitsky,et al.  Folylpolyglutamate synthetase mRNA G-quadruplexes regulate its cell protrusion localization and enhance a cancer cell invasive phenotype upon folate repletion , 2023, BMC Biology.

[2]  D. Frank,et al.  Cycloguanil and Analogues Potently Target DHFR in Cancer Cells to Elicit Anti-Cancer Activity , 2023, Metabolites.

[3]  J. Klumperman,et al.  Small molecules to regulate the GH/IGF1 axis by inhibiting the growth hormone receptor synthesis , 2022, Frontiers in Endocrinology.

[4]  Edward L. Huttlin,et al.  Proteome-wide mapping of short-lived proteins in human cells. , 2021, Molecular cell.

[5]  N. Neamati,et al.  A Review of Small-Molecule Inhibitors of One-Carbon Enzymes: SHMT2 and MTHFD2 in the Spotlight. , 2021, ACS pharmacology & translational science.

[6]  A. Vazquez,et al.  Folate metabolism: a re-emerging therapeutic target in haematological cancers , 2021, Leukemia.

[7]  Y. Assaraf,et al.  Folylpoly-ɣ-glutamate synthetase association to the cytoskeleton: Implications to folate metabolon compartmentalization. , 2021, Journal of proteomics.

[8]  M. Savitski,et al.  The functional proteome landscape of Escherichia coli , 2020, Nature.

[9]  Gregory A Landrum,et al.  Improving Conformer Generation for Small Rings and Macrocycles Based on Distance Geometry and Experimental Torsional-Angle Preferences , 2020, J. Chem. Inf. Model..

[10]  M. Savitski,et al.  Thermal proteome profiling for interrogating protein interactions , 2020, Molecular systems biology.

[11]  L. Matherly,et al.  Cellular Pharmacodynamics of a Novel Pyrrolo[3,2-d]pyrimidine Inhibitor Targeting Mitochondrial and Cytosolic One-Carbon Metabolism , 2019, Molecular Pharmacology.

[12]  Benjamin J. Raphael,et al.  Therapy-induced mutations drive the genomic landscape of relapsed acute lymphoblastic leukemia. , 2019, Blood.

[13]  M. Maurice,et al.  Three-dimensional analysis of single molecule FISH in human colon organoids , 2019, Biology Open.

[14]  L. Cantley,et al.  Toward a better understanding of folate metabolism in health and disease , 2018, The Journal of experimental medicine.

[15]  Martin Eisenacher,et al.  The PRIDE database and related tools and resources in 2019: improving support for quantification data , 2018, Nucleic Acids Res..

[16]  J. Blenis,et al.  Mitochondrial One-Carbon Pathway Supports Cytosolic Folate Integrity in Cancer Cells , 2018, Cell.

[17]  Matthew E Berginski,et al.  Coral: Clear and Customizable Visualization of Human Kinome Data. , 2018, Cell systems.

[18]  Peer Bork,et al.  Pervasive Protein Thermal Stability Variation during the Cell Cycle , 2018, Cell.

[19]  J. Asara,et al.  The mTORC1 Signaling Network Senses Changes in Cellular Purine Nucleotide Levels. , 2017, Cell reports.

[20]  R. Abraham,et al.  Purine Nucleotide Availability Regulates mTORC1 Activity through the Rheb GTPase. , 2017, Cell reports.

[21]  Joshua D Rabinowitz,et al.  One-Carbon Metabolism in Health and Disease. , 2017, Cell metabolism.

[22]  M. Bantscheff,et al.  Thermal profiling reveals phenylalanine hydroxylase as an off-target of panobinostat. , 2016, Nature chemical biology.

[23]  Karen H. Vousden,et al.  Serine and one-carbon metabolism in cancer , 2016, Nature Reviews Cancer.

[24]  G. Peters,et al.  Folylpolyglutamate synthetase splicing alterations in acute lymphoblastic leukemia are provoked by methotrexate and other chemotherapeutics and mediate chemoresistance , 2016, International journal of cancer.

[25]  G C P van Zundert,et al.  The HADDOCK2.2 Web Server: User-Friendly Integrative Modeling of Biomolecular Complexes. , 2016, Journal of molecular biology.

[26]  Sereina Riniker,et al.  Better Informed Distance Geometry: Using What We Know To Improve Conformation Generation , 2015, J. Chem. Inf. Model..

[27]  Toshiro Sato,et al.  Efficient genetic engineering of human intestinal organoids using electroporation , 2015, Nature Protocols.

[28]  G. Superti-Furga,et al.  Proteome-wide drug and metabolite interaction mapping by thermal-stability profiling , 2015, Nature Methods.

[29]  Víctor Segarra,et al.  Setup and validation of shake-flask procedures for the determination of partition coefficients (logD) from low drug amounts. , 2015, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[30]  M. Fenech,et al.  Biomarkers of Nutrition for Development-Folate Review. , 2015, The Journal of nutrition.

[31]  Hayley E. Francies,et al.  Prospective Derivation of a Living Organoid Biobank of Colorectal Cancer Patients , 2015, Cell.

[32]  Matthew E. Ritchie,et al.  limma powers differential expression analyses for RNA-sequencing and microarray studies , 2015, Nucleic acids research.

[33]  G. Drewes,et al.  Tracking cancer drugs in living cells by thermal profiling of the proteome , 2014, Science.

[34]  P. Johnston,et al.  Standing the test of time: targeting thymidylate biosynthesis in cancer therapy , 2014, Nature Reviews Clinical Oncology.

[35]  V. Mootha,et al.  Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer , 2014, Nature Communications.

[36]  A. Anderson,et al.  Elucidating features that drive the design of selective antifolates using crystal structures of human dihydrofolate reductase. , 2013, Biochemistry.

[37]  Adam Godzik,et al.  Divergent evolution of protein conformational dynamics in dihydrofolate reductase , 2013, Nature Structural &Molecular Biology.

[38]  K. Sohn,et al.  γ-Glutamyl hydrolase modulation and folate influence chemosensitivity of cancer cells to 5-fluorouracil and methotrexate , 2013, British Journal of Cancer.

[39]  P. Nordlund,et al.  Monitoring Drug Target Engagement in Cells and Tissues Using the Cellular Thermal Shift Assay , 2013, Science.

[40]  I. Goldman,et al.  Mechanisms of membrane transport of folates into cells and across epithelia. , 2011, Annual review of nutrition.

[41]  A. Anderson,et al.  2,4-Diamino-5-(2'-arylpropargyl)pyrimidine derivatives as new nonclassical antifolates for human dihydrofolate reductase inhibition. , 2011, Journal of molecular graphics & modelling.

[42]  Y. Assaraf,et al.  Aberrant splicing of folylpolyglutamate synthetase as a novel mechanism of antifolate resistance in leukemia. , 2009, Blood.

[43]  G. Peters,et al.  Gene expression profiling of leukemia T-cells resistant to methotrexate and 7-hydroxymethotrexate reveals alterations that preserve intracellular levels of folate and nucleotide biosynthesis. , 2009, Biochemical pharmacology.

[44]  M. Loh,et al.  Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children's Oncology Group study , 2008, Leukemia.

[45]  S. Kurup,et al.  Recent advances in classical and non-classical antifolates as antitumor and antiopportunistic infection agents: part I. , 2007, Anti-cancer agents in medicinal chemistry.

[46]  M. Lucock,et al.  Effects of folylpolyglutamate synthetase modulation on chemosensitivity of colon cancer cells to 5-fluorouracil and methotrexate , 2004, Gut.

[47]  R. Abagyan,et al.  Identification of protein-protein interaction sites from docking energy landscapes. , 2004, Journal of molecular biology.

[48]  I. Goldman,et al.  Resistance to antifolates , 2003, Oncogene.

[49]  P. Johnston,et al.  5-Fluorouracil: mechanisms of action and clinical strategies , 2003, Nature Reviews Cancer.

[50]  Y. Assaraf,et al.  Loss of folylpoly‐γ‐glutamate synthetase activity is a dominant mechanism of resistance to polyglutamylation‐dependent novel antifolates in multiple human leukemia sublines , 2003, International journal of cancer.

[51]  C. Dominguez,et al.  HADDOCK: a protein-protein docking approach based on biochemical or biophysical information. , 2003, Journal of the American Chemical Society.

[52]  David Weininger,et al.  SMILES. 2. Algorithm for generation of unique SMILES notation , 1989, J. Chem. Inf. Comput. Sci..

[53]  W. L. Jorgensen,et al.  The OPLS [optimized potentials for liquid simulations] potential functions for proteins, energy minimizations for crystals of cyclic peptides and crambin. , 1988, Journal of the American Chemical Society.

[54]  David Weininger,et al.  SMILES, a chemical language and information system. 1. Introduction to methodology and encoding rules , 1988, J. Chem. Inf. Comput. Sci..

[55]  Jacob D. Jaffe,et al.  Next-generation characterization of the Cancer Cell Line Encyclopedia , 2019, Nature.

[56]  S. Kurup,et al.  Recent advances in classical and non-classical antifolates as antitumor and antiopportunistic infection agents: Part II. , 2008, Anti-cancer agents in medicinal chemistry.

[57]  M. Mann,et al.  Protocol for micro-purification, enrichment, pre-fractionation and storage of peptides for proteomics using StageTips , 2007, Nature Protocols.

[58]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[59]  Y. Yamano,et al.  Severe complications after high-dose methotrexate treatment. , 1995, Acta oncologica.