Inosine monophosphate dehydrogenase (IMPDH), an NAD-dependent enzyme that controls de novo synthesis of guanine nucleotides, has received considerable interest in recent years as an important target enzyme, not only for the discovery of anticancer drugs, but also for antiviral, antiparasitic, and immunosuppressive chemotherapy. The field of IMPDH inhibitor research is highly important for providing potential therapeutics against a validated target for disease intervention. This patent review examines the chemical structures and biological activities of recently reported IMPDH inhibitors. Patent databases SciFinder and Espacenet and Delphion were used to locate patent applications that were published between January 2002 and July 2012, claiming chemical structures for use as IMPDH inhibitors. From 2002 to 2012, around 47 primary patent applications have claimed IMPDH inhibitors, which we analyzed by target and applicant. The level of newly published patent applications covering IMPDH inhibitors remains high and a diverse range of scaffolds has been claimed.
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Exp Hematol
December 2024
Division of Molecular Oncology, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Japan. Electronic address:
Nucleic acid analogs, including cytarabine, decitabine, and azacitidine, have significantly advanced therapeutic approaches for myeloid tumors over the past five decades. Nucleic acid metabolism is a crucial pathway driving myeloid tumorigenesis, with emerging evidence indicating that myeloid tumors are particularly dependent on the de novo nucleotide synthesis pathway, underscoring its potential as a therapeutic target. This review provides a comprehensive overview of nucleic acid metabolism, focusing on de novo nucleotide synthesis.
View Article and Find Full Text PDFActa Pharmacol Sin
November 2024
Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Tumor cells are characterized by rapid proliferation. In order to provide purines for DNA and RNA synthesis, inosine 5'-monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo guanosine biosynthesis, is highly expressed in tumor cells. In this study we investigated whether IMPDH was involved in cancer immunoregulation.
View Article and Find Full Text PDFbioRxiv
November 2024
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA.
Objective: Obesity is a major health concern, largely because it contributes to type 2 diabetes mellitus (T2DM), cardiovascular disease, and various malignancies. Increase in circulating amino acids and lipids, in part due to adipose dysfunction, have been shown to drive obesity-mediated diseases. Similarly, elevated purines and uric acid, a degradation product of purine metabolism, are found in the bloodstream and in adipose tissue.
View Article and Find Full Text PDFMicroorganisms
October 2024
Laboratory of Medical Zoology, Department of Microbiology, University of Massachusetts, Amherst, MA 01003, USA.
's inosine-5'-monophosphate dehydrogenase (IMPDH, GuaB encoded by the gene) is a potential therapeutic target. GuaB is necessary for replication in mammalian hosts but not in standard laboratory culture conditions. Therefore, we cannot test novel GuaB inhibitors against without utilizing mammalian infection models.
View Article and Find Full Text PDFEur J Med Chem
December 2024
School of Chemistry, University College Cork, Cork, Ireland; School of Pharmacy, University College Cork, Cork, Ireland; Analytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland. Electronic address:
Antimicrobial resistance poses a significant threat to global health, necessitating the development of novel therapeutic agents with unique mechanisms of action. Inosine 5'-monophosphate dehydrogenase (IMPDH), an essential enzyme in guanine nucleotide biosynthesis, is a promising target for the discovery of new antimicrobial agents. High-throughput screening studies have previously identified several urea-based leads as potential inhibitors, although many of these are characterised by reduced chemical stability.
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