ArticleMolecular cancer therapeutics2019
Novel Pyrrolo[3,2-
Erratum issuedOpen access · bronzeAbstract read
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Article in Molecular cancer therapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 46 papers.
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46citing papers in PubMed
2.0field-weighted citation impact, top 13% of its field
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Who cites it
46 citing papers in PubMed, 53 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
- SHMT2 inhibition triggers mitochondrial apoptosis to suppress lung adenocarcinoma progression.Journal of translational medicine · 2026Article
- Research on serine hydroxymethyltransferase 2 mechanisms in malignant tumor development and progression.PeerJ · 2026Review
- 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
- One-Carbon Metabolism Inhibition Depletes Purines and Results in Profound and Prolonged Ewing Sarcoma Growth Suppression.Cancer research communications · 2025Article
- The oncoprotein SET promotes serine-derived one-carbon metabolism by regulating SHMT2 enzymatic activity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- SHMT inhibitor synergizes with 5-Fu to suppress gastric cancer via cell cycle arrest and chemoresistance alleviation.NPJ precision oncology · 2025Article
- Inhibition Of One-Carbon Metabolism In Ewing Sarcoma Results In Profound And Prolonged Growth Suppression Associated With Purine Depletion.bioRxiv : the preprint server for biology · 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
- Tracing the Diverse Paths of One-Carbon Metabolism in Cancer and Beyond.Cold Spring Harbor perspectives in medicine · 2024Review
- Mitochondrial and Cytosolic One-Carbon Metabolism Is a Targetable Metabolic Vulnerability in Cisplatin-Resistant Ovarian Cancer.Molecular cancer therapeutics · 2024Article
- Cycling back to folate metabolism in cancer.Nature cancer · 2024Review
- Article
- Structural Characterization of 5-Substituted Pyrrolo[3,2-Biochemistry · 2024Article
- Discovery of Tumor-Targeted 6-Methyl Substituted Pemetrexed and Related Antifolates with Selective Loss of RFC Transport.ACS medicinal chemistry letters · 2023Article
- Multifaceted roles of mitochondrial dysfunction in diseases: from powerhouses to saboteurs.Archives of pharmacal research · 2023Review
- Structure-Based Design of Transport-Specific Multitargeted One-Carbon Metabolism Inhibitors in Cytosol and Mitochondria.Journal of medicinal chemistry · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
25 authors at 6 institutions in 2 countries.
Aamod S DekhneDepartment of Oncology, Wayne State University School of Medicine, and the Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.ORCID 0000-0002-2481-1858
Khushbu ShahDivision of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania.
Gregory S DuckerDepartment of Chemistry/Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey.ORCID 0000-0002-8651-6846
Jade M KatinasDepartment of Chemistry, Indiana University, Bloomington, Indiana.
Jennifer Wong-RousharDepartment of Chemistry, Indiana University, Bloomington, Indiana.ORCID 0000-0002-3278-3711
Md Junayed NayeenDivision of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania.
Arpit DoshiDivision of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania.
Changwen NingBiochemistry and Molecular Biology, Jilin University, Changchun, Jilin Province, China.
Xun BaoDepartment of Oncology, Wayne State University School of Medicine, and the Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Josephine FrühaufDepartment of Oncology, Wayne State University School of Medicine, and the Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Jenney LiuCenter for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan.
Adrianne Wallace-PovirkDepartment of Oncology, Wayne State University School of Medicine, and the Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Carrie O'ConnorDepartment of Oncology, Wayne State University School of Medicine, and the Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Sijana H DzinicDepartment of Oncology, Wayne State University School of Medicine, and the Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Kathryn WhiteDepartment of Oncology, Wayne State University School of Medicine, and the Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Juiwanna KushnerDepartment of Oncology, Wayne State University School of Medicine, and the Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Seongho KimDepartment of Oncology, Wayne State University School of Medicine, and the Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Maik HüttemannCenter for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan.
Lisa PolinDepartment of Oncology, Wayne State University School of Medicine, and the Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Joshua D RabinowitzDepartment of Chemistry/Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey.
Jing LiDepartment of Oncology, Wayne State University School of Medicine, and the Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Zhanjun HouDepartment of Oncology, Wayne State University School of Medicine, and the Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.ORCID 0000-0001-5631-5202
Charles E DannDepartment of Chemistry, Indiana University, Bloomington, Indiana. matherly@karmanos.org gangjee@duq.edu cedann@indiana.edu.
Aleem GangjeeDivision of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania. matherly@karmanos.org gangjee@duq.edu cedann@indiana.edu.
Larry H MatherlyDepartment of Oncology, Wayne State University School of Medicine, and the Barbara Ann Karmanos Cancer Institute, Detroit, Michigan. matherly@karmanos.org gangjee@duq.edu cedann@indiana.edu.
The Barbara Ann Karmanos Cancer Institute · USDuquesne University · USIndiana University Bloomington · USPrinceton University · USWayne State University · USJilin University · CN
Funding
Tumor Biology and Microenvironment (Program 1)P30CA022453 · NCI · WAYNE STATE UNIVERSITY · PI PAUL M STEMMER · 1985 to 2026
$68.4MTumor cell metabolism in actionR01CA163591 · NCI · RUTGERS, THE STATE UNIV OF N.J. · PI JOSHUA D RABINOWITZ, Eileen P. White · 2012 to 2026
$7.0MMOLECULAR REGULATION OF FOLATE AND ANTIFOLATE TRANSPORTR01CA053535 · NCI · WAYNE STATE UNIVERSITY · PI HOU, ZHANJUN, MATHERLY, LARRY H · 1993 to 2024
$6.3MMetabolism in Action: Quantitative Fluxes in MammalsDP1DK113643 · NIDDK · PRINCETON UNIVERSITY · PI RABINOWITZ, JOSHUA D · 2016 to 2020
$5.7MTRAINING 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
$2.3MMOLECULAR CORRELATES OF METHOTREXATE IN CHILDHOOD ALLR01CA076641 · NCI · WAYNE STATE UNIVERSITY · PI MATHERLY, LARRY H. · 1998 to 2007
$1.9MPurine Synthesis Inhibitors with Selective Folate Receptor Tumor TransportR01CA166711 · NCI · DUQUESNE UNIVERSITY · PI DANN, CHARLES E., GANGJEE, ALEEM · 2013 to 2015
$1.7MGlycine metabolism in cancer - Research Supplement to Promote Diversity in Health-Related Research; VelascoR00CA215307 · NCI · UNIVERSITY OF UTAH · PI DUCKER, GREGORY S · 2019 to 2021
$814kGlycine metabolism in cancerK99CA215307 · NCI · PRINCETON UNIVERSITY · PI DUCKER, GREGORY S · 2017 to 2018
$198kDual Targeting Cytosolic and Mitochondrial One-Carbon Metabolism with Novel 5-substituted PyrrolopyrimidinesF30CA228221 · NCI · WAYNE STATE UNIVERSITY · PI DEKHNE, AAMOD · 2018 to 2020
$143kTargeting 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 CA243215NCI NIH HHS K99 CA215307NCI NIH HHS P30 CA022453NCI NIH HHS R00 CA215307NCI NIH HHS R01 CA053535NCI NIH HHS R01 CA076641NCI NIH HHS R01 CA152316NCI NIH HHS R01 CA163591NCI NIH HHS R01 CA166711NCI NIH HHS T32 CA009531NIDDK NIH HHS DP1 DK113643
Abstract
Folate-dependent one-carbon (C1) metabolism is compartmentalized into the mitochondria and cytosol and supports cell growth through nucleotide and amino acid biosynthesis. Mitochondrial C1 metabolism, including serine hydroxymethyltransferase (SHMT) 2, provides glycine, NAD(P)H, ATP, and C1 units for cytosolic biosynthetic reactions, and is implicated in the oncogenic phenotype across a wide range of cancers. Whereas multitargeted inhibitors of cytosolic C1 metabolism, such as pemetrexed, are used clinically, there are currently no anticancer drugs that specifically target mitochondrial C1 metabolism. We used molecular modeling to design novel small-molecule pyrrolo[3,2-
Indexed as
AnimalsAntineoplastic AgentsBiosynthetic PathwaysCarbonCell Line, TumorCHO CellsCricetinaeCricetulusCytosolFemaleInhibitory Concentration 50MetabolomicsMice, SCIDMitochondriaPurinesPyrimidinesAntineoplastic AgentsCarbonPurinespyrimidinePyrimidinesPyrroles
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