Nucleoside Antimetabolite/Analog

SIBA selectively inhibits spermine synthase, IC50=8 uM.

Forodesine(BCX-1777 freebase; Immucillin-H) is an orally bioavailable PNP inhibitor with picomolar potency; induces apoptosis, mainly in T cells.

Forodesine hydrochloride (BCX-1777) is a highly potent and specific purine nucleoside phosphorylase (PNP) inhibitor.

7-Methylguanosine is a novel cNIIIB nucleotidase inhibitor with IC50 value of 87.8????7.5??M.

CI 972 is a potent, orally active, and competitive inhibitor of purine nucleoside phosphorylase (PNP) (Ki=0.83 μM) under development as a T cell-selective immunosuppressive agent.

Zalcitabine is a potent nucleoside analogue reverse transcriptase inhibitor used in the treatment of HIV infection.

Adenosine dialdehyde is a purine nucleoside analogue and a potent inhibitor of S-adenosylhomocysteine hydrolase (SAHH), with a Ki of 3.3 nM. By inhibiting SAHH, it disrupts methylation-dependent processes, contributing to its demonstrated anti-tumor activity in vivo. Adenosine dialdehyde is a valuable tool in cancer research, particularly in studies targeting epigenetic regulation and methylation pathways.

Netivudine is a nucleoside antimetabolite that acts as an analog inhibitor with significant antiviral activity against varicella zoster virus. In addition to its biological applications, Netivudine features an alkyne group, enabling its use in click chemistry through copper-catalyzed azide-alkyne cycloaddition (CuAAc). This reagent is valuable for molecular biology research and chemical biology applications, particularly in the development of novel therapeutic agents.

Dihydro-5-azacytidine acetate is a nucleoside analog that functions as a DNA methylation inhibitor. It is incorporated into DNA, leading to the disruption of normal methylation patterns. This compound exhibits notable antitumor activity and is utilized in research focused on cancer biology and epigenetic regulation.

BCX-5 is a selective inhibitor of purine nucleoside phosphorylase (PNP), offering an inhibitory potency with a Ki value of 0.08 μM. This compound is known to impede cell proliferation and modulate mixed lymphocyte reactions by elevating levels of inosine and guanosine in plasma. BCX-5 is valuable for research applications in immunology, providing insights into purine metabolism and lymphocyte function.

Dihydro-5-azacytidine is a DNA methylation inhibitor that is incorporated into the DNA structure, disrupting normal methylation processes. This compound exhibits antitumor activity, making it a valuable tool for cancer research. Its properties are relevant for studies focused on epigenetic regulation and the development of therapeutic strategies targeting DNA methylation.

CMX-521 is a nucleoside analog that functions as a potent inhibitor of the RNA-dependent RNA polymerase (RdRp) of norovirus. This compound effectively suppresses both murine norovirus (MNV) and human norovirus, making it a valuable tool for research into norovirus infections. Its inhibitory properties are essential for studies focused on antiviral development and mechanisms of norovirus replication.

5-Phenyluracil is a potent inhibitor of thymidine phosphorylase, an enzyme involved in nucleoside metabolism. This compound exhibits significant anti-tumor activity by disrupting the salvage pathway of nucleotides, making it relevant for cancer research. Its selective inhibition of thymidine phosphorylase highlights its potential utility in exploring cancer therapeutics and related biological pathways.

Nitrobenzylthioinosine 5'-monophosphate (NBMPR-P) is a prodrug of the effective nucleoside transport inhibitor Nitrobenzylthioinosine (NBMPR). This compound primarily functions by blocking nucleoside transport in vivo, thereby mitigating host toxicity during high-dose Tubercidin treatment in tumor-bearing mice. NBMPR-P is valuable in research applications focusing on nucleoside transport mechanisms and related therapeutic interventions.

5'-dUMPS is a competitive inhibitor of enzymes interacting with 2'-deoxypyrimidine-5'-monophosphate. It plays a crucial role in modulating nucleic acid synthesis and can be utilized in research focused on metabolic pathways and enzyme kinetics. Its capacity to regulate enzyme activity makes it a valuable tool for studies in molecular biology and pharmacology.

Brivoligide (AYX1) is a double-stranded, unprotected oligonucleotide composed of 23 base pairs, functioning as a pain inhibitor. It has demonstrated efficacy in reducing acute post-surgical pain through its ability to mimic the DNA sequence typically bound by the transcription factor EGR1 on chromosomes. This unique mechanism makes Brivoligide a valuable tool for research applications focused on pain management and therapeutic interventions in pain-related conditions.

Homouridine is an uridine analogue that acts as an MMP-2 inhibitor, exhibiting an IC50 of 150 μM for compound I. This compound demonstrates significant biological activity through its ability to inhibit TNF-α binding to the TNF-αR1, making it valuable for research applications focused on inflammatory responses and extracellular matrix remodeling. Homouridine serves as a vital intermediate in the synthesis of MMP-2 inhibitors, facilitating studies in cancer and tissue repair mechanisms.

MANT-GppNHp is a competitive inhibitor of adenylate cyclase (AC) that serves as a fluorescently labeled GTP analogue. It specifically interacts with the hydrophobic pocket adjacent to the AC catalytic site through its MANT group, effectively obstructing the binding of ATP. This compound is valuable for investigating diseases characterized by elevated AC activity, such as cholera, and offers insights into cellular signaling pathways.

Immucillin-G is a potent inhibitor of purine nucleoside phosphorylase (PNP), a key enzyme in purine metabolism. By inhibiting PNP, Immucillin-G effectively reduces urate levels, making it valuable for research into metabolic disorders, particularly hyperuricemia. Its role in modulating purine metabolism provides significant insights for studies related to gout and metabolic diseases.

Ap5dT is an inhibitor of cytosolic thymidine kinase and mitochondrial enzymes, exhibiting inhibition constants (Kis) of 0.12 μM and 0.50 μM, respectively. This compound is relevant for research on acute myelocytic leukemia, facilitating investigations into thymidine metabolism and its implications in cancer biology. Its selective inhibition properties make Ap5dT a valuable tool for studying metabolic pathways involved in cellular proliferation.

Guanosine 3',5'-bisdiphosphate (ppGpp) acts as a specific inhibitor of guanylate kinases, affecting GTP biosynthesis in chloroplasts. By inhibiting plastid and mitochondrial guanylate kinase activity, ppGpp is crucial for understanding metabolic regulation and signaling processes in plant systems. This reagent is valuable for research applications involving nucleotide metabolism and signaling pathways.

HD202A is a selective dual inhibitor of MNK1 and MNK2, exhibiting IC50 values of 6.09 nM and 8.06 nM, respectively. This compound effectively inhibits the MNK-eIF4E signaling pathway, leading to downregulation of perilipin 2 and SCD1, while upregulating adipose triglyceride lipase and PPARγ coactivator 1α. HD202A enhances mitochondrial fatty acid oxidation, redox homeostasis, and demonstrates significant effects on metabolic health, including suppression of body weight gain, reduction in hepatic lipid accumulation, and improvement in glucose tolerance and insulin sensitivity. These properties make HD202A a valuable tool for researching metabolic dysfunction-associated steatotic liver disease.

KIN59 (5’-O-Tritylinosine) is a potent allosteric inhibitor of thymidine phosphorylase, effectively impacting cellular proliferation. This compound demonstrates the ability to inhibit FGF2-stimulated cell growth and reduces the expression of phosphorylated FGFR1 and Akt in FGF2-stimulated cells. KIN59 showcases significant anti-tumor activity, making it valuable for research in cancer therapeutics and cell signaling pathways.

RGB097 is a potent inhibitor of D-dopachrome tautomerase (D-DT), demonstrating an IC50 value of 0.5 µM. This compound exhibits significant biological activity and has potential applications in cancer research, particularly in elucidating the role of D-DT in oncogenesis and tumor progression.

MIF-IN-5 is a potent and reversible inhibitor of macrophage migration inhibitory factor (MIF), exhibiting a competitive mechanism of action. With an IC50 of 4.8 μM and a Ki value of 3.3 μM, it effectively disrupts MIF's biological activity. This compound is valuable for research applications involving inflammation, immune response modulation, and potential therapeutic strategies targeting various diseases associated with MIF dysregulation.

HTS05585 is a selective inhibitor of macrophage migration inhibitory factor (MIF), demonstrating a Kd value of 0.29 μM via microscale thermophoresis and 0.32±0.01 μM confirmed by isothermal titration calorimetry. This compound effectively inhibits the release of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, from LPS-stimulated macrophages. HTS05585 is a valuable tool for studying inflammation-related diseases, particularly in the context of sepsis research.

TE-11 is a potent MIF tautomerase inhibitor, exhibiting an IC50 value of 5.63 μM. This compound effectively ameliorates CD-like colitis and reduces migration of MIF-induced eosinophils and neutrophils. Additionally, TE-11 prevents M1 polarization and the associated metabolic reprogramming, making it a valuable tool for research in inflammatory and autoimmune disorders.