Related Experiment Video

Updated: Nov 20, 2025

Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells
08:11

Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells

Published on: August 7, 2021

4.4K

Targeting prenylation inhibition through the mevalonate pathway

Pimyupa Manaswiyoungkul1, Elvin D de Araujo2, Patrick T Gunning2,1

  • 1Department of Chemistry , University of Toronto , 80 St. George Street , Toronto , Ontario M5S 3H6 , Canada.

RSC Medicinal Chemistry
|January 22, 2021
PubMed

Insights

Protein prenylation is key in diseases like cancer and AIDS. Targeting upstream enzymes offers a new strategy to inhibit prenylation and cholesterol synthesis, potentially overcoming drug resistance.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Protein prenylation is a crucial biological process implicated in diseases such as cancer and AIDS.
  • Current therapies targeting prenyltransferase enzymes (FTase, GGTase I/II) face challenges including off-target effects, drug resistance, and suboptimal potency.

Purpose of the Study:

  • To explore an alternative therapeutic strategy by targeting upstream mevalonate pathway enzymes (FPPS, GGPPS).
  • To investigate the potential of dual inhibition of prenylation and cholesterol synthesis for improved therapeutic outcomes.

Main Methods:

  • Review of current research on prenylation inhibitors.
  • Analysis of the mevalonate pathway and its key enzymes (FPPS, GGPPS).
  • Discussion of novel inhibitor development strategies.

Main Results:

  • Direct targeting of prenyltransferase enzymes has shown limited clinical success due to resistance and side effects.
  • Inhibiting upstream enzymes (FPPS, GGPPS) offers a dual approach to block prenylation and cholesterol synthesis.
  • This alternative strategy presents opportunities to overcome existing therapeutic limitations.

Conclusions:

  • Targeting FPPS and GGPPS represents a promising avenue for developing novel therapeutics against cancer and AIDS.
  • Dual inhibition of prenylation and cholesterol synthesis may offer enhanced efficacy and overcome drug resistance mechanisms.
  • Further development of inhibitors against the prenylation machinery is warranted.

More Related Videos

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

13.5K
Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.4K

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.3K
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
3.3K
Feedback Inhibition00:46

Feedback Inhibition

Biochemical reactions are occurring constantly in cells, converting starting substances to different products, usually with the help of enzymes that speed the reactions. Without enzymes, it would take far too long for most reactions to occur to be useful to the cell!
56.2K
Biosynthesis of Nucleic Acids01:28

Biosynthesis of Nucleic Acids

Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
546
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.0K
Enzyme Inhibition01:30

Enzyme Inhibition

Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
88.8K