Ornithine Decarboxylase Inhibition: A Strategy to Combat Various Diseases
Rakesh R Somani1, Priyanshu R Rai1, Pooja S Kandpile1
1Department of Pharmaceutical Chemistry, Vivekanand Education Society`s College of Pharmacy, Chembur (E), Mumbai 400074, India.
Mini Reviews in Medicinal Chemistry
|October 4, 2017
Summary
Ornithine decarboxylase (ODC) inhibition targets polyamines crucial for cell growth. While Eflornithine (DFMO) showed early promise in cancer, its broader applications now include infectious diseases and hirsutism.
Area of Science:
- Biochemistry
- Pharmacology
- Molecular Biology
Background:
- Polyamines (putrescine, spermidine, spermine) are essential for cellular functions like growth, DNA stabilization, and gene expression.
- Elevated polyamine levels are characteristic of rapidly proliferating tumor cells, making their synthesis pathway a target for cancer therapy.
- Ornithine decarboxylase (ODC) is the rate-limiting enzyme in polyamine biosynthesis, catalyzing the conversion of ornithine to putrescine.
Purpose of the Study:
- To explore the role of ornithine decarboxylase (ODC) and polyamines in cellular processes and disease.
- To review the therapeutic applications and limitations of ODC inhibitors, particularly Eflornithine (DFMO).
- To discuss the development of novel ODC inhibitors for various diseases.
Main Methods:
- Review of existing literature on polyamine metabolism and ODC inhibitors.
- Analysis of Eflornithine's efficacy and challenges in cancer treatment.
- Examination of Eflornithine's success in treating African sleeping sickness and hirsutism.
- Discussion of ongoing research into new ODC-targeting analogs for tropical diseases.
Main Results:
- Eflornithine (DFMO), an irreversible ODC inhibitor, was initially explored for anticancer properties but faced limitations.
- Polyamines are critical in various infectious microorganisms, leading to Eflornithine's successful use in treating African sleeping sickness.
- Eflornithine is also effective for managing hirsutism in women.
- New analogs targeting ODC are being synthesized to combat diseases like Leishmaniasis and Malaria.
Conclusions:
- ODC and polyamine metabolism are vital targets for therapeutic intervention across diverse diseases.
- While Eflornithine's anticancer role is limited, its efficacy in other conditions highlights the potential of targeting this pathway.
- Continued development of ODC inhibitors offers promising avenues for treating infectious and proliferative diseases.
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