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Further proteomics studies have shown that QD394 can effectively reduce the expression of proteins in mitochondria (mainly down-regulate the mitochondrial proteins LRPPRC and PNPT1)
.
Figure 9 Combined use with FDA approved drugs
The combination of QD394 and existing FDA-approved drugs (including Napabucasin, As2O3 and olaparib) found that QD394 and these drugs showed a certain synergistic anti-cancer ability
.
Figure 10 Pharmacokinetic data
The above-mentioned research shows that QD394 has significant potential for the development of pancreatic cancer drugs, but follow-up pharmacokinetic studies show that QD394 is poor in plasma stability, with a half-life of only 6 minutes
.
Therefore, researchers have further developed QD394-Me with better pharmacokinetic data (see Figure 11 for the structural formula), and its plasma half-life can reach more than 120 minutes (Figure 10)
.
Figure 11.
Development and mechanism of QD394-Me
The efficacy and function evaluation of QD394-Me showed that the mechanism of action of QD394-Me is similar to that of QD394, and at the same time it has better efficacy
.
Figure 12 QD394-Me drug efficacy and function evaluation
The development of pancreatic cancer from QD394 to QD394-Me not only provides two drug molecules, QD394 and QD394-Me, but also provides the possibility for further pancreatic cancer drug development; at the same time, the combination of this type of drug molecule with existing marketed drug molecules can show It has a synergistic effect and has the potential for development of combination drugs
.
It is expected that such drug molecules will be launched as soon as possible to benefit the majority of pancreatic cancer patients
.
references:
1.
A Novel Redox Modulator Induces a GPX4-Mediated Cell Death That Is Dependent on Iron and Reactive Oxygen Species, 2020.