ArticleJournal of medicinal chemistry2013
Development and binding mode assessment of N-[4-[2-propyn-1-yl[(6S)-4,6,7,8-tetrahydro-2-(hydroxymethyl)-4-oxo-3H-cyclopenta[g]quinazolin-6-yl]amino]benzoyl]-l-γ-glutamyl-D-glutamic acid (BGC 945), a novel thymidylate synthase inhibitor that targets tumor cells.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- MTHFD2: a promising metabolic checkpoint for diseases.Journal of translational medicine · 2026Review
- Folate Receptor Alpha-A Secret Weapon in Ovarian Cancer Treatment?International journal of molecular sciences · 2024Review
- Therapeutic strategies targeting folate receptor α for ovarian cancer.Frontiers in immunology · 2023Review
- A Phase I Trial of CT900, a Novel α-Folate Receptor-Mediated Thymidylate Synthase Inhibitor, in Patients with Solid Tumors with Expansion Cohorts in Patients with High-Grade Serous Ovarian Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Folic Acid-Peptide Conjugates Combine Selective Cancer Cell Internalization with Thymidylate Synthase Dimer Interface Targeting.Journal of medicinal chemistry · 2021Article
- Development of a Pemetrexed/Folic Acid Nanoformulation: Synthesis, Characterization, and Efficacy in a Murine Colorectal Cancer Model.ACS omega · 2020Article
- Exploiting the folate receptor α in oncology.Nature reviews. Clinical oncology · 2020Review
- Formulation of Folate-Modified Raltitrexed-Loaded Nanoparticles for Colorectal Cancer Theranostics.Pharmaceutics · 2020Article
- IgE Antibodies: From Structure to Function and Clinical Translation.Antibodies (Basel, Switzerland) · 2019Review
- Anti-Folate Receptor Alpha-Directed Antibody Therapies Restrict the Growth of Triple-negative Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- A Modified System for the Synthesis of Enantioenriched N-Arylamines through Copper-Catalyzed Hydroamination.Angewandte Chemie (International ed. in English) · 2018Article
- Mg2+ binds to the surface of thymidylate synthase and affects hydride transfer at the interior active site.Journal of the American Chemical Society · 2013Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
N-[4-[2-Propyn-1-yl[(6S)-4,6,7,8-tetrahydro-2-(hydroxymethyl)-4-oxo-3H-cyclopenta[g]quinazolin-6-yl]amino]benzoyl]-l-γ-glutamyl-d-glutamic acid 1 (BGC 945, now known as ONX 0801), is a small molecule thymidylate synthase (TS) inhibitor discovered at the Institute of Cancer Research in London. It is licensed by Onyx Pharmaceuticals and is in phase 1 clinical studies. It is a novel antifolate drug resembling TS inhibitors plevitrexed and raltitrexed that combines enzymatic inhibition of thymidylate synthase with α-folate receptor-mediated targeting of tumor cells. Thus, it has potential for efficacy with lower toxicity due to selective intracellular accumulation through α-folate receptor (α-FR) transport. The α-FR, a cell-surface receptor glycoprotein, which is overexpressed mainly in ovarian and lung cancer tumors, has an affinity for 1 similar to that for its natural ligand, folic acid. This study describes a novel synthesis of 1, an X-ray crystal structure of its complex with Escherichia coli TS and 2'-deoxyuridine-5'-monophosphate, and a model for a similar complex with human TS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.