ArticleMolecular pharmacology2020
Cellular Pharmacodynamics of a Novel Pyrrolo[3,2-
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Article in Molecular pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29citing papers in PubMed
1.2field-weighted citation impact, top 21% of its field
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Who cites it
29 citing papers in PubMed, 35 citations in OpenAlex.
- Comparative binding and activity analysis of known serine hydroxymethyltransferase inhibitors in biochemical assays.RSC advances · 2026Article
- Serine Hydroxymethyltransferase (SHMT) in biology and disease: molecular mechanisms and therapeutic targeting.Journal of translational medicine · 2026Review
- Research on serine hydroxymethyltransferase 2 mechanisms in malignant tumor development and progression.PeerJ · 2026Review
- Article
- Multifaceted role of serine hydroxymethyltransferase in health and disease.Molecules and cells · 2025Review
- Pharmacodynamic determinants of mitochondrial one-carbon flux and serine hydroxymethyltransferase inhibition in human tumors.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Folate induces stemness and increases oxygen consumption under glucose deprivation by notch-1 pathway activation in colorectal cancer cell.Molecular and cellular biochemistry · 2025Article
- Mechanism and Therapeutic Progress of One-Carbon Metabolic Key Enzyme: Serine Hydroxymethyltransferase 2 in Cancer.Clinical Medicine Insights. Oncology · 2025Review
- Role of Mitochondrial and Cytosolic Folylpolyglutamate Synthetase in One-Carbon Metabolism and Antitumor Efficacy of Mitochondrial-Targeted Antifolates.Molecular pharmacology · 2024Article
- Mitochondrial and Cytosolic One-Carbon Metabolism Is a Targetable Metabolic Vulnerability in Cisplatin-Resistant Ovarian Cancer.Molecular cancer therapeutics · 2024Article
- Structural Characterization of 5-Substituted Pyrrolo[3,2-Biochemistry · 2024Article
- Targeting one-carbon metabolism for cancer immunotherapy.Clinical and translational medicine · 2024Review
- Discovery of Tumor-Targeted 6-Methyl Substituted Pemetrexed and Related Antifolates with Selective Loss of RFC Transport.ACS medicinal chemistry letters · 2023Article
- A novel antifolate suppresses growth of FPGS-deficient cells and overcomes methotrexate resistance.Life science alliance · 2023Article
- Structure-Based Design of Transport-Specific Multitargeted One-Carbon Metabolism Inhibitors in Cytosol and Mitochondria.Journal of medicinal chemistry · 2023Article
- Methotrexate Provokes Disparate Folate Metabolism Gene Expression and Alternative Splicing in Ex Vivo Monocytes and GM-CSF- and M-CSF-Polarized Macrophages.International journal of molecular sciences · 2023Article
- Serine-associated one-carbon metabolic reprogramming: a new anti-cancer therapeutic strategy.Frontiers in oncology · 2023Review
- The Influence of Mitochondrial Energy and 1C Metabolism on the Efficacy of Anticancer Drugs: Exploring Potential Mechanisms of Resistance.Current medicinal chemistry · 2023Review
- Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management.Journal of hematology & oncology · 2022Review
- Targeting cancer metabolism in the era of precision oncology.Nature reviews. Drug discovery · 2022Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 2 countries.
Aamod S DekhneDepartment of Oncology, Wayne State University School of Medicine/Karmanos Cancer Institute, Detroit, Michigan (A.S.D., J.F., A.W.-P., C.O., Z.H., S.K., L.H.M.); Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., A.G.); Center for Molecular Medicine and Genetics (H.K., M.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Biochemistry and Molecular Biology, Jilin University, Changchun, Jilin Province, China (C.N.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (Z.H., S.K., M.H., L.H.M.).ORCID 0000-0002-2481-1858
Changwen NingDepartment of Oncology, Wayne State University School of Medicine/Karmanos Cancer Institute, Detroit, Michigan (A.S.D., J.F., A.W.-P., C.O., Z.H., S.K., L.H.M.); Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., A.G.); Center for Molecular Medicine and Genetics (H.K., M.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Biochemistry and Molecular Biology, Jilin University, Changchun, Jilin Province, China (C.N.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (Z.H., S.K., M.H., L.H.M.).
Md Junayed NayeenDepartment of Oncology, Wayne State University School of Medicine/Karmanos Cancer Institute, Detroit, Michigan (A.S.D., J.F., A.W.-P., C.O., Z.H., S.K., L.H.M.); Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., A.G.); Center for Molecular Medicine and Genetics (H.K., M.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Biochemistry and Molecular Biology, Jilin University, Changchun, Jilin Province, China (C.N.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (Z.H., S.K., M.H., L.H.M.).
Khushbu ShahDepartment of Oncology, Wayne State University School of Medicine/Karmanos Cancer Institute, Detroit, Michigan (A.S.D., J.F., A.W.-P., C.O., Z.H., S.K., L.H.M.); Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., A.G.); Center for Molecular Medicine and Genetics (H.K., M.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Biochemistry and Molecular Biology, Jilin University, Changchun, Jilin Province, China (C.N.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (Z.H., S.K., M.H., L.H.M.).
Hasini KalpageDepartment of Oncology, Wayne State University School of Medicine/Karmanos Cancer Institute, Detroit, Michigan (A.S.D., J.F., A.W.-P., C.O., Z.H., S.K., L.H.M.); Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., A.G.); Center for Molecular Medicine and Genetics (H.K., M.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Biochemistry and Molecular Biology, Jilin University, Changchun, Jilin Province, China (C.N.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (Z.H., S.K., M.H., L.H.M.).
Josephine FrühaufDepartment of Oncology, Wayne State University School of Medicine/Karmanos Cancer Institute, Detroit, Michigan (A.S.D., J.F., A.W.-P., C.O., Z.H., S.K., L.H.M.); Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., A.G.); Center for Molecular Medicine and Genetics (H.K., M.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Biochemistry and Molecular Biology, Jilin University, Changchun, Jilin Province, China (C.N.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (Z.H., S.K., M.H., L.H.M.).
Adrianne Wallace-PovirkDepartment of Oncology, Wayne State University School of Medicine/Karmanos Cancer Institute, Detroit, Michigan (A.S.D., J.F., A.W.-P., C.O., Z.H., S.K., L.H.M.); Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., A.G.); Center for Molecular Medicine and Genetics (H.K., M.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Biochemistry and Molecular Biology, Jilin University, Changchun, Jilin Province, China (C.N.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (Z.H., S.K., M.H., L.H.M.).
Carrie O'ConnorDepartment of Oncology, Wayne State University School of Medicine/Karmanos Cancer Institute, Detroit, Michigan (A.S.D., J.F., A.W.-P., C.O., Z.H., S.K., L.H.M.); Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., A.G.); Center for Molecular Medicine and Genetics (H.K., M.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Biochemistry and Molecular Biology, Jilin University, Changchun, Jilin Province, China (C.N.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (Z.H., S.K., M.H., L.H.M.).
Zhanjun HouDepartment of Oncology, Wayne State University School of Medicine/Karmanos Cancer Institute, Detroit, Michigan (A.S.D., J.F., A.W.-P., C.O., Z.H., S.K., L.H.M.); Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., A.G.); Center for Molecular Medicine and Genetics (H.K., M.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Biochemistry and Molecular Biology, Jilin University, Changchun, Jilin Province, China (C.N.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (Z.H., S.K., M.H., L.H.M.).
Seongho KimDepartment of Oncology, Wayne State University School of Medicine/Karmanos Cancer Institute, Detroit, Michigan (A.S.D., J.F., A.W.-P., C.O., Z.H., S.K., L.H.M.); Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., A.G.); Center for Molecular Medicine and Genetics (H.K., M.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Biochemistry and Molecular Biology, Jilin University, Changchun, Jilin Province, China (C.N.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (Z.H., S.K., M.H., L.H.M.).
Maik HüttemannDepartment of Oncology, Wayne State University School of Medicine/Karmanos Cancer Institute, Detroit, Michigan (A.S.D., J.F., A.W.-P., C.O., Z.H., S.K., L.H.M.); Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., A.G.); Center for Molecular Medicine and Genetics (H.K., M.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Biochemistry and Molecular Biology, Jilin University, Changchun, Jilin Province, China (C.N.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (Z.H., S.K., M.H., L.H.M.).
Aleem GangjeeDepartment of Oncology, Wayne State University School of Medicine/Karmanos Cancer Institute, Detroit, Michigan (A.S.D., J.F., A.W.-P., C.O., Z.H., S.K., L.H.M.); Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., A.G.); Center for Molecular Medicine and Genetics (H.K., M.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Biochemistry and Molecular Biology, Jilin University, Changchun, Jilin Province, China (C.N.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (Z.H., S.K., M.H., L.H.M.) gangjee@duq.edu.
Larry H MatherlyDepartment of Oncology, Wayne State University School of Medicine/Karmanos Cancer Institute, Detroit, Michigan (A.S.D., J.F., A.W.-P., C.O., Z.H., S.K., L.H.M.); Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania (M.J.N., K.S., A.G.); Center for Molecular Medicine and Genetics (H.K., M.H.) and Department of Pharmacology (L.H.M.), Wayne State University School of Medicine, Detroit, Michigan; Biochemistry and Molecular Biology, Jilin University, Changchun, Jilin Province, China (C.N.); and Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan (Z.H., S.K., M.H., L.H.M.) matherly@karmanos.org.
Duquesne University · US
Funding
Tumor Biology and Microenvironment (Program 1)P30CA022453 · NCI · WAYNE STATE UNIVERSITY · PI Julie Lynn Boerner · 1985 to 2026
$68.4MMOLECULAR REGULATION OF FOLATE AND ANTIFOLATE TRANSPORTR01CA053535 · NCI · WAYNE STATE UNIVERSITY · PI HOU, ZHANJUN, MATHERLY, LARRY H · 1993 to 2024
$6.3MTRAINING PROGRAM IN THE BIOLOGY OF CANCERT32CA009531 · NCI · WAYNE STATE UNIVERSITY · PI Larry H Matherly · 1985 to 2026
$5.3MDiscovery of novel PCFT-targeted agentsR01CA152316 · NCI · WAYNE STATE UNIVERSITY · PI GANGJEE, ALEEM, MATHERLY, LARRY H · 2011 to 2015
$2.3MPurine Synthesis Inhibitors with Selective Folate Receptor Tumor TransportR01CA166711 · NCI · DUQUESNE UNIVERSITY · PI DANN, CHARLES E., GANGJEE, ALEEM · 2013 to 2015
$1.7MDual Targeting Cytosolic and Mitochondrial One-Carbon Metabolism with Novel 5-substituted PyrrolopyrimidinesF30CA228221 · NCI · WAYNE STATE UNIVERSITY · PI DEKHNE, AAMOD · 2018 to 2020
$143kTherapeutic Targeting of Novel Antifolates to Solid Tumors via Folate ReceptorF31CA165853 · NCI · WAYNE STATE UNIVERSITY · PI MITCHELL, SHERMAINE KIMBERLY · 2011 to 2014
$111kTargeting Mitochondrial One-Carbon Metabolism in Epithelial Ovarian CancerF31CA243215 · NCI · WAYNE STATE UNIVERSITY · PI WALLACE-POVIRK, ADRIANNE · 2019 to 2020
$85kNCI NIH HHS F30 CA228221NCI NIH HHS F31 CA165853NCI NIH HHS F31 CA243215NCI NIH HHS P30 CA022453NCI NIH HHS R01 CA053535NCI NIH HHS R01 CA152316NCI NIH HHS R01 CA166711NCI NIH HHS T32 CA009531
Abstract
Folate-dependent one-carbon (C1) metabolism is compartmentalized in the mitochondria and cytosol and is a source of critical metabolites for proliferating tumors. Mitochondrial C1 metabolism including serine hydroxymethyltransferase 2 (SHMT2) generates glycine for de novo purine nucleotide and glutathione biosynthesis and is an important source of NADPH, ATP, and formate, which affords C1 units as 10-formyl-tetrahydrofolate and 5,10-methylene-tetrahydrofolate for nucleotide biosynthesis in the cytosol. We previously discovered novel first-in-class multitargeted pyrrolo[3,2-
Indexed as
Antineoplastic AgentsCell Line, TumorCell MembraneCytosolDrug Screening Assays, AntitumorGene Knockout TechniquesGlutathioneGlycine HydroxymethyltransferaseHumansLeucovorinMitochondriaPancreatic NeoplasmsPurine NucleotidesPyrimidinesPyrrolesReactive Oxygen Species10-formyltetrahydropteroylglutamic acid5,10-methylenetetrahydrofolic acidAntineoplastic AgentsGlutathioneGlycine HydroxymethyltransferaseLeucovorinPurine NucleotidesPyrimidinesPyrrolesPyrrolo(2,3-d)pyrimidineReactive Oxygen SpeciesSerineSHMT protein, humanTetrahydrofolates
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