FOXO4-DRI CAS NO.2460055-10-9

Aging and many diseases are largely caused by the accumulation of damaged cells that no longer divide. The scientists found that inhibitors of FOXO4 protein activity cleared senescent cells in mice. If the cell is badly damaged, it may enter a self-clearing process called apoptosis, or a self-disabling process called aging. Since senescent cells can survive for a long time, they accumulate in aging and damaged organs. A range of evidence has shown that eliminating senescent cells extends healthy life in mice and reduces the severity of age-related diseases. Baar et al. 's paper, published in Cell, deepens our understanding of this phenomenon. They noted that the survival of senescent cells depended on the transcription factor FOXO4. Meanwhile, mouse models show that tissue dysfunction and age-related diseases caused by chemotherapy can be reversed by pharmacological interference with FOXO4 function. Senescent cells inhibit their ability to proliferate as they reprogram, while secreting signaling molecules -a phenomenon known as senescence-associated secretory phenotype (SASP). Scientists believe that the normal function of SASP is to restore tissue function in two ways: first, by stimulating less damaged adjacent cells to participate in tissue repair; Second, eliminate senescent cells by attracting inflammatory cells and turn off SASP-mediated signaling. However, this repair process may fail when the extent, duration, or frequency of damage exceeds repair capacity, or when SASP can no longer stimulate repair and attract inflammatory cells. The end result is abnormal accumulation of senescent cells, exacerbating tissue dysfunction. Over the past two years, several studies have shown that senescent cells, due to their apparent molecular vulnerability, can be targeted with compounds - drugs that preferentially kill senescent cells. Senescent cells express high levels of pro-apoptotic and anti-apoptotic factors, so they always hover on the edge of cell death. This is the theoretical basis for the preparation of typical anti-aging drugs. These drugs inhibit the action of the BCL-2 protein family (a family of proteins that promote cell survival) and guide cells into the process of apoptosis. The scientists have also proposed an anti-aging formula based on a combination of two drugs, but the specific molecular basis remains to be elucidated. Gene expression data showed that the transcription factor FOXO4 was up-regulated in senescent cells compared to normal cells. Baar further noted that downregulation of FOXO4 using inhibitory RNA molecules induces apoptosis in senescent cells, but not in normal cells, while downregulation of other FOXO family members does not have this effect. To some extent, FOXO4 and some of its family members promote cell survival through interactions with multiple protein partners. According to Baar et al., FOXO4 is an important molecule that promotes the survival of senescent cells. Interestingly, FOXO4 can interact with the protein p53, a known age-inducing protein. The researchers therefore reasoned that this FOXO4-p53 interaction may be essential for the survival of senescent cells, and that disrupting this interaction would drive apoptosis (Figure 1). To test this, they synthesized a modified peptide fragment known as FOXO4-D reverse transcription (FOXO4-DRI). This peptide fragment lacks the normal transcriptional activity of FOXO4, but binds to p53 more stably and can therefore competitively inhibit FoxO4-p53 interactions.

Purity (HPLC) ≥98.0%

Single impurity≤2%

Peptide content≥75.0%

Amino Acid Composition≤±15%

Bacterial Endotoxins≤50EU/mg

Solubility：H₂O/DMSO

Vacuum-packed with aluminum foil bag or transparent bag.Various weights can be packed according to your requirements.

Storage:Cool dry place( Store at -20°C, away from the light)

Remark:For Research Use Only. Not for human use.

Aging and many diseases are largely caused by the accumulation of damaged cells that no longer divide. The scientists found that inhibitors of FOXO4 protein activity cleared senescent cells in mice. If the cell is badly damaged, it may enter a self-clearing process called apoptosis, or a self-disabling process called aging. Since senescent cells can survive for a long time, they accumulate in aging and damaged organs. A range of evidence has shown that eliminating senescent cells extends healthy life in mice and reduces the severity of age-related diseases. Baar et al. 's paper, published in Cell, deepens our understanding of this phenomenon. They noted that the survival of senescent cells depended on the transcription factor FOXO4. Meanwhile, mouse models show that tissue dysfunction and age-related diseases caused by chemotherapy can be reversed by pharmacological interference with FOXO4 function. Senescent cells inhibit their ability to proliferate as they reprogram, while secreting signaling molecules -a phenomenon known as senescence-associated secretory phenotype (SASP). Scientists believe that the normal function of SASP is to restore tissue function in two ways: first, by stimulating less damaged adjacent cells to participate in tissue repair; Second, eliminate senescent cells by attracting inflammatory cells and turn off SASP-mediated signaling. However, this repair process may fail when the extent, duration, or frequency of damage exceeds repair capacity, or when SASP can no longer stimulate repair and attract inflammatory cells. The end result is abnormal accumulation of senescent cells, exacerbating tissue dysfunction. Over the past two years, several studies have shown that senescent cells, due to their apparent molecular vulnerability, can be targeted with compounds - drugs that preferentially kill senescent cells. Senescent cells express high levels of pro-apoptotic and anti-apoptotic factors, so they always hover on the edge of cell death. This is the theoretical basis for the preparation of typical anti-aging drugs. These drugs inhibit the action of the BCL-2 protein family (a family of proteins that promote cell survival) and guide cells into the process of apoptosis. The scientists have also proposed an anti-aging formula based on a combination of two drugs, but the specific molecular basis remains to be elucidated. Gene expression data showed that the transcription factor FOXO4 was up-regulated in senescent cells compared to normal cells. Baar further noted that downregulation of FOXO4 using inhibitory RNA molecules induces apoptosis in senescent cells, but not in normal cells, while downregulation of other FOXO family members does not have this effect. To some extent, FOXO4 and some of its family members promote cell survival through interactions with multiple protein partners. According to Baar et al., FOXO4 is an important molecule that promotes the survival of senescent cells. Interestingly, FOXO4 can interact with the protein p53, a known age-inducing protein. The researchers therefore reasoned that this FOXO4-p53 interaction may be essential for the survival of senescent cells, and that disrupting this interaction would drive apoptosis (Figure 1). To test this, they synthesized a modified peptide fragment known as FOXO4-D reverse transcription (FOXO4-DRI). This peptide fragment lacks the normal transcriptional activity of FOXO4, but binds to p53 more stably and can therefore competitively inhibit FoxO4-p53 interactions.