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Review
. 2022 Mar 5;13(3):466.
doi: 10.3390/genes13030466.

Recent Development of Prodrugs of Gemcitabine

Bhoomika Pandit  1 , Maksim Royzen  1
Affiliations
Review

Recent Development of Prodrugs of Gemcitabine

Bhoomika Pandit et al. Genes (Basel). .

Abstract

Gemcitabine is a nucleoside analog that has been used widely as an anticancer drug for the treatment of a variety of conditions, including ovarian, bladder, non-small-cell lung, pancreatic, and breast cancer. However, enzymatic deamination, fast systemic clearance, and the emergence of chemoresistance have limited its efficacy. Different prodrug strategies have been explored in recent years, seeking to obtain better pharmacokinetic properties, efficacy, and safety. Different drug delivery strategies have also been employed, seeking to transform gemcitabine into a targeted medicine. This review will provide an overview of the recent developments in gemcitabine prodrugs and their effectiveness in treating cancerous tumors.

Keywords: anticancer agent; chemotherapy; drug delivery; gemcitabine; prodrug.

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Conflict of interest statement

Maksim Royzen is an advisor and shareholder of Shasqi, Inc.

Figures

Figure 1
Figure 1
A library of prodrugs of GCB containing hydrophobic monophosphate ester modifications.
Figure 2
Figure 2
(A) Prodrugs of GCB, S-Gem and C-Gem. (B) Mechanism of enzymatic activation of S-Gem.
Figure 3
Figure 3
Mechanism of activation of A-Gem by hydrogen peroxide.
Figure 4
Figure 4
Prodrugs of GCB, containing various amino acids conjugated to the N4-position of the nucleobase.
Figure 5
Figure 5
Proposed mechanisms of activation of prodrugs Albumin-1a and Albumin-1b.
Figure 6
Figure 6
Prodrugs of GCB that can be uncaged by bio-orthogonal palladium Pd0 chemistry.
Figure 7
Figure 7
The structure of GCB-TCO-acid and the mechanism of its activation by Tz via bond-cleaving bio-orthogonal IEDDA chemistry.
Figure 8
Figure 8
CAPAC platform for local activation of systemically administered prodrugs to treat cancer.
See this image and copyright information in PMC

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