Nucleoside and non-nucleoside IMP dehydrogenase inhibitors as antitumor and antiviral agents.

  title={Nucleoside and non-nucleoside IMP dehydrogenase inhibitors as antitumor and antiviral agents.},
  author={Palmarisa Franchetti and Mario Grifantini},
  journal={Current medicinal chemistry},
  volume={6 7},
IMP dehydrogenase (IMPDH) is an enzyme which catalyzes the NAD-dependent conversion of inosine 5 -monophosphate (IMP) to xanthosine 5 -monophosphate (XMP) at the metabolic branch point in the de novo purine nucleotide synthetic pathway. IMPDH was shown to be increased significantly in cancer cells and therefore considered to be a sensitive target for cancer chemotherapy. By blocking the conversion of IMP to XMP, IMPDH inhibitors lead to depletion of the guanylate (GMP, GDP, GTP and dGTP) pools… 

Inhibitors of the IMPDH Enzyme as Potential Anti-Bovine Viral Diarrhoea Virus Agents

Previously unreported IMPDH inhibitors that have potent anti-BVDV activity are identified, namely: C6-MPAlc (5), C 6-MPA-Me (7), C4-MP alc (8), C 4-M PA (10) and C2-MAD (20).

Synthesis of Azole Nucleoside 5′‐Monophosphate Mimics (P1Ms) and Their Inhibitory Properties of IMP Dehydrogenases

A series of azole nucleoside 5′‐MP mimics (P1Ms) based on ribavirin, EICAR and bredinin were synthesized and screened against human and C. albicans IMP dehydrogenises, demonstrating substantial IMPDH inhibition with Ki values in low micromolar range.

Repurposing existing drugs: identification of irreversible IMPDH inhibitors by high-throughput screening

In the preliminary efficacy experiment against cryptosporidiosis in severe combined immunodeficiency mouse, a decrease in the number of oocyst shed was observed upon the oral administration of disulfiram and bronopol, providing an early clinical proof-of-concept for further utilization of these compounds as IMPDH inhibitors.

From ribavirin to NAD analogues and back to ribavirin in search for anticancer agents

Ribavirin adenine dinucleotide did not show any significant inhibition at the enzymatic level, and was clearly established that its antitumor activity is related to the inhibition of an oncogene, the eukaryotic translation initiation factor (eIF4E).

Virtual and experimental high-throughput screening (HTS) in search of novel inosine 5′-monophosphate dehydrogenase II (IMPDH II) inhibitors

A ligand-based virtual screening using IMPDH inhibitor pharmacophore models was performed on in-house compound collection and 7 interesting classes were discovered which represent structurally novel chemotypes which can be taken up for further development.

Regulation of the Interaction of Inosine Monophosphate Dehydrogenase with Mycophenolic Acid by GTP*

It is concluded that intracellular GTP acts as an antagonist to MPA by directly binding to IMPDH and reversing the conformational changes in the protein.

Characterization of Pharmacological Efficacy of VX-148, a New, Potent Immunosuppressive Inosine 5′-Monophosphate Dehydrogenase Inhibitor

It is demonstrated that VX-148 is a potent and specific IMPDH inhibitor with a favorable pharmacokinetic profile and good pharmacological activity in mice, and thus support development of V X-148 as an immunosuppressive drug.


In this study, the role of inosine monophosphate dehydrogenase at the metabolic branch point of de novo purine nucleotide biosynthesis makes this enzyme an attractive probe for the discovery of antiviral compounds, and some of the parent nucleosides exhibited antiviral activity.


Nucleoside and Non-nucleoside IMP Dehydrogenase- Inhibitors as Antitumor and Antiviral Agents

It was hypothesized that the inhibitory activity of tiazofurin is due to an attractive electrostatic interaction between the heterocyclic sulphur atom and the furanose oxygen 1' which constrain rotation about the C-glycosidic bond in tiazo-4- carboxamide adenine dinucleotide and in its active anabolite TAD.