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FOXO4-DRI (Proxofim) (10mg)
$270.00
FOXO4-DRI peptides are Synthesized and Lyophilized in the USA.
Discount per Quantity
Quantity | 5 - 9 | 10 + |
---|---|---|
Discount | 5% | 10% |
Price | $256.50 | $243.00 |
FREE - 30ml bottle of bacteriostatic water
(Required for reconstitution)
FREE - USPS priority shipping
Description
What is the FOXO4-DRI peptide?
FOXO4-DRI is a synthetic version of FOXO4, containing D amino acids instead of L amino acids. This modification is intended to allow the peptide to retain the functionality of the original protein with a longer shelf life and lower clearance from the body. Its most prominent function is suggested to be the regulation of apoptosis in senescent cells[1]. It appears to inhibit FOXO4-p53 binding, thereby p53 may target pro-apoptotic genes and promote their expression. These proteins, in turn, may bring about apoptosis of old cells, thereby reducing the old cell burden in tissues. This increases cellular differentiation, tissue repair, and regrowth and decreases “biological age.” FOXO4 protein is a prominent member of the group of transcription factors that have the potential to regulate growth and differentiation. It is abundant in tissues such as the placenta, ovaries, fat cells, testes, and adrenal glands. Post-translational modifications, especially those in the DNA binding domain of FOXO4 protein, appear to modify its functionality as a transcription factor and regulation of pathways such as apoptosis, cellular senescence, insulin signaling, and senescence. FOXO4-D-Retro-Inverso is a synthetic ad partially altered form of the original FOXO4 protein. The modification was developed to help enhance the half-life of the protein and allows it to obstruct the normal FOXO4 function. FOXO4-DRI has been suggested to prevent normal FOXO4 binding to p53, eliminating of senescent cells, enhancing organ function, and reducing “biological age.” FOXO4-DRI appears to influence insulin signaling, cell cycle regulation, and oxidative stress signaling pathways. The peptide appears to be permeable into cells and has been suggested by researchers to selectively induce senescent cell apoptosis, thereby reversing aging effects in animal studies.
Specifications
AKA: Forkhead box protein O4, Proxofim, FOXO4a, AFX, AFX1, MLLT7
Sequence: H-D-Leu-D-Thr-D-Leu-D-Arg-D-Lys-D-Glu-D-Pro-D-Ala-D-Ser-D-Glu-D-Ile-D-Ala-D-Gln-D-Ser-D-Ile-D-Leu-D-Glu-D-Ala-D-Tyr-D-Ser-D-Gln-D-Asn-D-Gly-D-Trp-D-Ala-D-Asn-D-Arg-D-Arg-D-Ser-D-Gly-D-Gly-D-Lys-D-Arg-D-Pro-D-Pro-D-Pro-D-Arg-D-Arg-D-Arg-D-Gln-D-Arg-D-Arg-D-Lys-D-Lys-D-Arg-D-Gly-OH
Molecular Formula: C228H388N86O64
Molecular Weight: 5358.05 g/mol
Reconstitution: Required
FOXO4-DRI Research
DRI peptides are synthetic variants of their natural counterparts. The synthetic alternatives have the sequence of amino acids reversed as well as the alpha chirality changed[2]. Naturally occurring amino acids have L chiral configuration, while the DRI peptides appear to be composed of D chiral amino acids. This has the potential to protect the synthetic peptides from enzymatic degradation and longer bioavailability. This leads to prolonged functional viability. They are also potential candidates for peptidomimetics for the study of protein-protein, protein-peptide, and peptide-peptide interactions. Biopharmaceuticals also prefer D peptides due to their apparent resistance to degradation, longer bioavailability, and low immunogenicity compared to their L counterparts.
FOXO4-DRI and Research in Aging, Senescence
FOXO4 is suggested to help the perpetuation of aged or senescent cells. It appears to bind to p53 and thereby may prevent apoptotic death of the senescent cells[3]. The DRI peptide appears to prevent FOXO4-p53 interaction, thus p53 may activate apoptotic protein and induce cellular death. Thus the old cells may be cleared from tissues, naturally allowing for better tissue regeneration. Studies have observed treatment of aging mice with the DRI peptide has improved tissue regeneration and healthspan. Healthspan refers to the tenure of lifespan wherein the body remains active. It decreases with age. Tissue renewal can certainly reduce the biological aging of tissues and thereby enhance the health span of an individual. The aged mice exhibited a longer healthy life span, greater physical activity, lesser observed disability such as cardiac diseases and musculoskeletal dysfunction, etc.
FOXO4-DRI and Research in Insulin Signal Regulation
FOXO proteins are suggested to regulate the influence of insulin signaling and insulin-like growth factors. Scientific evidence suggests that the FOXO family of proteins act downstream of insulin signaling to regulate cellular growth, metabolism, differentiation, and oxidative stress. Mutations in FOXO genes have been suggested to cause diabetic toxicity such as hyperglycemia and hyperlipidemia and even lead to cancer. In the context of diabetes, it may lead to heart attack, impaired wound healing, stroke, and kidney damage, to name a few. Targeting FOXO signaling in the milieu of diabetes may lead to effective and targeted treatment regimens without any disease complications[4]. The exact mechanism of FOXO4-DRI signaling is yet unknown. It is opined to reduce fasting blood sugar levels, thereby controlling diabetes.
FOXO4-DRI and Research in Heart Disease
Age is one of the critical factors which influence the onset of cardiac disease. The reason has been ascribed to loss of proteasome activity with age. Proteasome helps in the degradation of oxidized, modified, or damaged proteins, thereby keeping the cellular environment healthy. Reduction in proteasome functionality leads to the accumulation of toxic protein, which can be detrimental to cardiac tissues[5]. FOXO signaling appears to have the potential to increase autophagy and proteasomal activity in the heart, clearing out damaged cells. It is thought that FOXO4-DRI protein or any variant of it may promote proteasomal functions, enhancing the health of cardiac tissues and reducing the risk of cardiovascular disease.
FOXO4-DRI and Research in Neurodegenerative diseases
The complex etiology of neurodegenerative diseases is yet to be completely understood. There is evidence that indicates the alteration in FOXO proteins to be a contributor to the disease etiology[6]. A decrease in proteasomal activity enhances the underlying condition of Huntington’s disease, Alzheimer’s disease, Parkinson’s, and Prion disease. Hence, FOXO-DRI protein or other modified alternatives may be valuable in treating the conditions by substituting for the absence of native FOXO proteins.
Conclusion
The synthetic peptide thus holds a lot of promise concerning a stable alternative to indigenous FOXO4 protein. The composition appears to allow it to retain the functionality of the original protein while overcoming the enzymatic degradation. Thus its bioavailability appears to be enhanced with sustained physiological effects. More extensive and dedicated research has the potential to unravel the precise mechanism of the FOXO4-DRI protein in disease biology and amelioration such as diabetes, cancer, Alzheimer’s, Parkinson’s, cardiac disease, dementia, and cellular senescence. At present, the peptide is available only for animal experiments, and human consumption has not been approved. The modified protein FOXO4-DRI has been reported by researchers to exhibit excellent subcutaneous and low oral bioavailability in mice where it is administered.
References
- Huang Y, He Y, Makarcyzk MJ, Lin H. Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes. Front Bioeng Biotechnol. 2021 Apr 29;9:677576. doi: 10.3389/fbioe.2021.677576. PMID: 33996787; PMCID: PMC8116695.
- Doti N, Mardirossian M, Sandomenico A, Ruvo M, Caporale A. Recent Applications of Retro-Inverso Peptides. Int J Mol Sci. 2021 Aug 12;22(16):8677. doi: 10.3390/ijms22168677. PMID: 34445382; PMCID: PMC8395423.
- Baar MP, Brandt RMC, Putavet DA, Klein JDD, Derks KWJ, Bourgeois BRM, Stryeck S, Rijksen Y, van Willigenburg H, Feijtel DA, van der Pluijm I, Essers J, van Cappellen WA, van IJcken WF, Houtsmuller AB, Pothof J, de Bruin RWF, Madl T, Hoeijmakers JHJ, Campisi J, de Keizer PLJ. Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell. 2017 Mar 23;169(1):132-147.e16. doi: 10.1016/j.cell.2017.02.031. PMID: 28340339; PMCID: PMC5556182.
- Murakami T, Inagaki N, Kondoh H. Cellular Senescence in Diabetes Mellitus: Distinct Senotherapeutic Strategies for Adipose Tissue and Pancreatic β Cells. Front Endocrinol (Lausanne). 2022 Mar 31;13:869414. doi: 10.3389/fendo.2022.869414. PMID: 35432205; PMCID: PMC9009089.
- Zhu M, Zhang QJ, Wang L, Li H, Liu ZP. FoxO4 inhibits atherosclerosis through its function in bone marrow derived cells. Atherosclerosis. 2011 Dec;219(2):492-8. doi: 10.1016/j.atherosclerosis.2011.09.038. Epub 2011 Oct 2. PMID: 22005198; PMCID: PMC3226872.
- Bourgeois B, Madl T. Regulation of cellular senescence via the FOXO4-p53 axis. FEBS Lett. 2018 Jun;592(12):2083-2097. doi: 10.1002/1873-3468.13057. Epub 2018 May 25. PMID: 29683489; PMCID: PMC6033032.
Dr. Usman (BSc, MBBS, MaRCP) completed his studies in medicine at the Royal College of Physicians, London. He is an avid researcher with more than 30 publications in internationally recognized peer-reviewed journals. Dr. Usman has worked as a researcher and a medical consultant for reputable pharmaceutical companies such as Johnson & Johnson and Sanofi.
Additional information
Brand | Biotech Peptides |
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23 reviews for FOXO4-DRI (Proxofim) (10mg)
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Niall Calder –
I had to wait 2 weeks for restocking which wasn’t ideal. Come up with a better system
Ariana Malik –
my trusted source
Chuck Northrop –
No hit and miss like other peptide sources. Each and every product that I bought here, has worked flawlessly. I highly recommend their products.
Matt Bryant –
I ordered peptides for the first time and I had no idea what to expect, but they were kind enough to put me in touch with someone who took the time to explain to to me all the details I needed to know. Thank you fro being patient with me.
Greg Kirby –
A++
Vikram Nair –
This is a first time in my career that I have worked with a peptide research company that I am happy with
Joe Mick –
Great job, I got no complaints.
Penny King –
I like to do research on companies before I do busniess with them. So far, I would highly recommend Biotech Peptides to any researcher or company! Products are pure and true!
Gary O’Neal –
Love the free bac water it came with!! pleasant surprise 🙂
Michelle Zkiab –
My company has been super happy with the products from Biotech! it has been about 3 months now that we have switched over and we’ve just placed our 10th order!
Yixing Liu –
偉大的產品,非常純淨
Joe Samaniego –
Not one to write reviews, but wanted to praise the company for the great service and the good quality products. I’ve been in the game a while now and had issues with my previous peptide supplier. Heard about Biotech from a friend and decided to test them out. No bs with them, they know their products and I let them know if I like their products that I’d love to work an arrangment out for consistent shipments and orders and possibly a better deal due to buying in bulk and buying as frequently as I will be. They had no issues with it, gave a great deal and happy with my decision.
Carolyn Rider –
I love their CS. They always answer any questions I have on the spot
Brynn Libermen –
They’re great at getting issues handled on a timely matter. Staff knows what they’re doing!
Casper Stone –
I have shopped with them before but this time they screwed up my order. Had to call and get it straightened out. They refunded me and overnighted the products I ACTUALLY needed. Happy about the refund, upset there was even a screw up. Products came in a day. Quality is always great and have never had any issues with the purity or performance of the peptides. Shit happens but hopfully not again.
Elie Rizk –
They have the best quality products!!! My only concern is I see they run out of products fast. Guess they’re getting pretty popular.
Philip Jones –
Nothing came broken, everything was packaged correctly. Seemed secure enough for me.
marc dennings –
My package got lost in transit and they were able to rush me a new one free of any charges. Amazing.
K.C. Stephens –
Peptides have good storage life. Have had some leftover from projects and was happy I didn’t have to repurchase any when I started a new project.
Brit K. Anders –
Best peptides I have come across in the last 10 years I have been working with it.
Tyler Goss –
New to the peptide game and Biotech has been the one and only site I buy my peptides from. Service is out of this world amazing and professional. Peptides are equally as good as the service.
Ryan Conner –
Staff is great and they are all pretty informed about all aspects of peptides. Rarely do you get an “I don’t know” to a question.
Shawn Riordan –
Nice variety of peptides and they have a lot of topical options as well which you don’t see too often.