FOXO4-DRI powder
Other names:Forkhead box O transcription factor 4-D-Retro-Inverso, Proxofim, D-Retro Inverso Forkhead box protein O4, FOXO4-D-retro-inverso
FOXO4-D-Retro-Inverso(DRI) is a synthetic, slightly modified version of the standard FOXO4 protein. The modification prolongs half-life of the protein and allows it to interfere with normal FOXO4 function. FOXO4-DRI has been shown in research to prevent normal FOXO4 binding to p53, thereby allowing for elimination of senescent cells, improved organ function, and younger tissue “biological age.” FOXO4-DRI impacts insulin signaling, cell cycle regulation, and oxidative stress signaling pathways. FOXO4-DRI is a cell penetrating peptide shown to selectively induce apoptosis of senescent cells thereby reversing effects of aging in animal studies.
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Properties
Description
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Properties
Sequence: | H-LTLRKEPASEIAQSILEAYSQNGWANRRSGGKRPPPRRRQRRKKRG-OH |
Molecular Formula: | C228H388N86O64 |
Molecular Weight: | 5358.05 g/mol |
PubChem CID: | / |
CAS Number: | 2460055-10-9 |
Synonyms: | Forkhead box O transcription factor 4-D-Retro-Inverso, Proxofim, D-Retro Inverso Forkhead box protein O4, FOXO4-D-retro-inverso |
Description
Structure of FOXO4-DRI
What Is FOXO4-DRI?
FOXO4-DRI is a synthetic peptide designed to block the interaction between two proteins, forkhead box O 4 (FOXO4) and p53. This interaction is involved in maintaining the viability of senescent (aged) cells. By preventing FOXO4 from targeting p53 to the nucleus, FOXO4-DRI allows p53 to induce apoptosis (cell death) in these senescent cells. [1][5][7][9]
FOXO4-D-Retro-Inverso is a modified version of the standard FOXO4 protein. This modification extends the half-life of the protein and enables it to interfere with the normal function of FOXO4. FOXO4-DRI has been shown in research to disrupt the normal binding of FOXO4 to p53, leading to the elimination of senescent cells. This can result in improved organ function and a reduction in the “biological age” of the tissue.[3][4][12][13]
Furthermore, FOXO4-DRI affects various cellular processes, including insulin signaling, cell cycle regulation, and oxidative stress signaling pathways. It is a cell-penetrating peptide, meaning it can enter cells and exert its effects from within. In animal studies, FOXO4-DRI has demonstrated the ability to selectively induce apoptosis in senescent cells, potentially reversing some effects of aging.[4][5][7][9]
What is FOXO4-DRI of structure and function?
FOXO4 is a member of the forkhead family transcription factors O subclass, which is characterized by a winged helix domain used for DNA binding. There are 4 members of the FOXO family, including FOXO1, FOXO3, and FOXO6. Their activity is modified by many post translational activities, such as phosphorylation,[6][8][10][11] ubiquitination, and acetylation Depending on this modified state, FOXO4 binding affinity for DNA is altered, allowing for FOXO4 to regulate many cellular pathways including oxidative stress signaling, longevity, insulin signaling, cell cycle progression, and apoptosis. Two of the main upstream regulators of FOXO4 activity are phosphoinositide 3- kinase (PI3K) and serine/threonine kinase AKT/PKB. Both PI3K and AKT modify FOXO4 and prevent it from translocating to the nucleus, effectively preventing the transcription of the downstream FOXO targets.
How does FOXO4-DRI work?
FOXO4-DRI is a peptide that is believed to have the potential to target and eliminate senescent cells selectively. Senescent cells are cells that have entered a state of irreversible growth arrest and are associated with aging and age-related diseases. FOXO4-DRI’s mechanism of action is designed to specifically target these senescent cells while sparing healthy cells, primarily through the use of D-amino acids instead of L-amino acids.[11][12][13]
Here’s how FOXO4-DRI is thought to work:
Selective Penetration of Senescent Cells
FOXO4-DRI is designed with specific sequences of D-amino acids, which makes it more resistant to enzymatic degradation and protein metabolism. This peptide is believed to have an enhanced ability to penetrate senescent cells compared to normal, healthy cells.
Disruption of FOXO4-p53 Interaction
Within senescent cells, there is an interaction between FOXO4 and p53, two important proteins involved in regulating cell growth and senescence. FOXO4-DRI is thought to prevent the binding and interaction between FOXO4 and p53. This disruption may interfere with the maintenance of senescent cell viability.[6][9][11][13]
Senescence Induction and High Glucose Environment
The passage in your text about senescence induction in a high glucose environment is likely unrelated to FOXO4-DRI but is important background information. Senescence can indeed be induced by various factors, including oxidative stress and changes in gene expression. In a high glucose environment, it is suggested that there is an increased production of reactive oxygen species (ROS), decreased expression of sirtuin 1 (SIRT1), and subsequent acetylation of FOXO1 and p53. These molecular changes can contribute to the upregulation of p21, a protein associated with cell cycle arrest and senescence.
In summary, FOXO4-DRI is designed to selectively target senescent cells by using D-amino acids, resist degradation, and disrupt the interaction between FOXO4 and p53. Its goal is to eliminate these senescent cells, which are thought to contribute to aging and age-related diseases, while leaving healthy cells unharmed. However, it’s important to note that the development and efficacy of FOXO4-DRI may still be a subject of ongoing research and clinical investigation.[9][10][12][14]
What are the benefits of FOXO4-DRI?
Forkhead box O4 (FOXO4) is a transcription factor and a member of the FOXO family of proteins. FOXO proteins are known for their role in regulating various cellular processes through transcriptional activity, and FOXO4, in particular, plays several important functions in the cell. Some of its key functions include:
Regulation of Gene Expression
FOXO4 regulates the transcription (gene expression) of numerous target genes. These target genes are involved in a wide range of cellular processes, including metabolism, cell cycle control, apoptosis (programmed cell death), oxidative stress response, and DNA repair. By controlling the expression of these genes, FOXO4 helps maintain cellular homeostasis and respond to environmental stresses.
Cell Cycle Regulation
FOXO4 can influence the cell cycle by regulating the expression of genes that control cell division. It can induce cell cycle arrest, which is a temporary halt in the cell cycle, allowing the cell to repair DNA damage or respond to other cellular signals before proceeding with cell division.[8][9][10][13]
Apoptosis
FOXO4 is involved in apoptosis, a programmed cell death process. It can activate the expression of genes that promote apoptosis, allowing cells to undergo controlled cell death when necessary. This is important for removing damaged or potentially harmful cells from the body.
Metabolism
FOXO4 plays a role in metabolic regulation by influencing the expression of genes involved in glucose metabolism, lipid metabolism, and insulin signaling. It can help maintain glucose homeostasis and respond to changes in nutrient availability.
Oxidative Stress Response
FOXO4 is part of the cellular response to oxidative stress, which occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the cell’s ability to detoxify them. FOXO4 can activate genes that enhance the cell’s antioxidant defenses to counteract oxidative damage.[1][5][7][9]
Cellular Homeostasis
Overall, FOXO4 contributes to the maintenance of cellular homeostasis by orchestrating the expression of genes involved in various cellular processes. It helps the cell adapt to changing conditions and respond to stressors to ensure its survival and function.
It’s important to note that the functions of FOXO4 can vary depending on the cellular context and the specific genes it regulates. FOXO4 is part of a complex regulatory network that interacts with other proteins and signaling pathways to fine-tune cellular responses to different stimuli and maintain overall cellular health.[11][14][15]
Can FOXO4-DRI treats low testosterone?
There is a hypothesis that FOXO4-DRI may have therapeutic potential in treating male late-onset hypogonadism. Hypogonadism refers to a condition in which the body produces insufficient amounts of testosterone,[1][5][7][9] which can lead to a variety of symptoms including reduced libido, fatigue, muscle loss, and mood changes.
Here’s how FOXO4-DRI is thought to be related to the treatment of male late-onset hypogonadism based on the information you provided:
FOXO4 and Testosterone Synthesis. FOXO4 is expressed in human Leydig cells, which are responsible for testosterone synthesis in the testes. The translocation of FOXO4 to the nucleus in elderly individuals is associated with decreased testosterone synthesis. This suggests that FOXO4 may play a role in regulating testosterone production.
FOXO4 in Senescent Leydig Cells. In vitro experiments using senescent Leydig cells showed that FOXO4 helps maintain the viability of these cells and suppresses their apoptosis (cell death).[3][6][8][12] Senescent Leydig cells may contribute to reduced testosterone production in aging males.
FOXO4-DRI’s Mechanism. FOXO4-DRI, a specific FOXO4 blocker, disrupts the interaction between FOXO4 and p53. This disruption selectively induces p53 nuclear exclusion and apoptosis in senescent Leydig cells. This suggests that FOXO4-DRI may help eliminate these senescent cells.
Therapeutic Potential. In naturally aged mice, FOXO4-DRI was reported to improve the testicular microenvironment and alleviate age-related testosterone secretion insufficiency. This implies that FOXO4-DRI may have therapeutic potential for addressing the hormonal imbalances associated with male late-onset hypogonadism.
It’s important to note that these findings are based on research conducted in animals and in vitro models, and the translation of such research to effective treatments in humans can be complex and challenging. Additionally, the efficacy and safety of FOXO4-DRI for treating male late-onset hypogonadism would need to be rigorously tested in clinical trials before it could be considered a viable treatment option.
Could FOXO4-DRI be used for hair loss?
It’s suggested that FOXO4-DRI had a positive impact on fur density in mice, specifically in XpdTTD/TTD mice that experience accelerated hair loss as part of their aging phenotype. While these findings are intriguing, it’s important to approach the potential use of FOXO4-DRI for hair loss in humans with caution and consider the following points:
Mice vs. Humans. Mice and humans have different physiology and genetic makeup. What works in mice may not necessarily have the same effect in humans. [1][7][9]Hair loss in humans is a complex and multifactorial condition, often influenced by genetics, hormones, aging, and various other factors.
Specific Mouse Model. The improvement in fur density observed in FOXO4-DRI-treated XpdTTD/TTD mice might be specific to this particular mouse model and its unique characteristics. It’s uncertain whether similar effects would be observed in other models or in humans.
Safety and Efficacy. The safety and efficacy of FOXO4-DRI for promoting hair growth in humans have not been established through clinical trials. Before any substance can be considered a viable treatment for hair loss in humans,[11][13][15]it must undergo extensive testing to ensure its safety and effectiveness.
Regulatory Approval. Any treatment for hair loss intended for human use would need to go through regulatory approval processes in various countries, such as the FDA in the United States. This involves demonstrating safety and efficacy through rigorous clinical trials.
Dosing and Application. Even if FOXO4-DRI were found to have potential for hair growth in humans, determining the appropriate dosing, route of administration, and safety profile for topical or systemic use would be crucial.
In summary, while the observed effects of FOXO4-DRI on fur density in mice are interesting, it’s far from conclusive evidence that it could be a treatment for human hair loss. Hair loss is a complex issue with many contributing factors, and potential treatments need to be thoroughly researched and tested in humans before they can be considered safe and effective for this purpose.[2][3][4][6]
FOXO4-DRI side effects and safety
There is limited information available about the specific side effects of FOXO4-DRI, as it was still in the experimental and preclinical stages of development. It’s important to note that when evaluating potential side effects of any experimental or investigational drug or treatment, the information may change as further research is conducted.
If you are considering or participating in clinical trials involving FOXO4-DRI or any experimental treatment,[2][6][8][11] it is essential to work closely with healthcare professionals and researchers who can monitor your health, provide guidance, and document any side effects or adverse reactions. They can also inform you about the latest information regarding the safety profile of the treatment.
Storage FOXO4-DRI
FOXO4 D-Retro-Inverso(DRI) should be stored in a freezer at or below -9C. After reconstitution, FOXO4 D-Retro-Inverso(DRI) peptide should be kept refrigerated.
FOXO4-DRI For Sale | FOXO4-DRI supplier
FOXO4 is a protein that belongs to the Forkhead box O (FOXO) family of transcription factors. These proteins play important roles in regulating various cellular processes, including cell cycle control, DNA repair, oxidative stress response, and apoptosis (programmed cell death). FOXO4, in particular, is involved in the regulation of genes related to cell survival and cell death. Researchers interested in experimenting with FOXO4-DRI will want to ensure that they source this material from a reliable supplier. lf you’re looking to buying FOXO4-DRI online,[10][11][13][15]it is essential to exercise caution and ensure that you obtain the powder from a reputable and trustworthy manufacuturer. peptide.ltd is a highly reliable manufacturer that offers pharmaceutical grade powder.
Manufacturers/Factory
FOXO4-DRI is designed to block the interaction between FOXO4 and p53.[1][5][7][9] This interaction normally allows FOXO4 to target p53 to the nucleus of the cell, where p53 can induce apoptosis (cell death). By blocking this interaction, FOXO4-DRI may prevent FOXO4 from inhibiting p53-mediated apoptosis, potentially promoting the death of senescent (aged) cells. If you are looking for the professional and top peptide FOXO4-DRI manufacturer or factory, here is the right place where you are.
The research mentioned suggests that FOXO4-DRI could be a potential tool for eliminating senescent cells, which are cells that have ceased to divide and can accumulate in tissues as a person ages.[2][3][6][9] The elimination of senescent cells has been studied as a potential approach to address some of the effects of aging and age-related diseases.
As the best FOXO4-DRI powder manufacturer,[11][13][15] peptide.ltd is not only supply the powder FOXO4-DRI in powder form but provide the customized standard easy use vial form.
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FAQ
What is FOXO4-DRI?
FOXO4-DRI is a peptide antagonist designed to block the interaction of forkhead box O 4 (FOXO4) and p53 [24]. Using ionizing radiation-induced senescent IMR90 cells,[1][5][7]it was observed that FOXO4 maintains senescent cell viability by targeting p53 to the nucleus and preventing it from inducing apoptosis.
What is mechanism of FOXO4-DRI?
FOXO4-DRI, a specific FOXO4 blocker, disrupts the interaction between FOXO4 and p53. This disruption selectively induces p53 nuclear exclusion and apoptosis in senescent Leydig cells. This suggests that FOXO4-DRI may help eliminate these senescent cells.
What is FOXO4-DRI used for?
❶ Increased Energy. Some proponents of FOXO4-DRI suggest that its ability to selectively target and eliminate senescent cells could lead to improved tissue and organ function. Senescent cells are associated with aging and age-related diseases, and removing them could potentially result in increased vitality and overall energy levels. However, clinical evidence supporting this claim is limited.
❷ May Improve Osteoarthritis Treatments. Osteoarthritis is a degenerative joint disease often associated with aging. Senescent cells have been implicated in the progression of osteoarthritis. FOXO4-DRI’s potential to target senescent cells may lead to improvements in osteoarthritis treatment by reducing the burden of these cells in affected joints. Again, this is a concept that requires further research and clinical validation.
❸ May Be Useful in Reducing side effects of Cancer Treatments. Some cancer treatments, such as chemotherapy and radiation therapy, can have side effects on healthy cells and tissues. The selective removal of senescent cells by FOXO4-DRI could theoretically reduce some of these side effects by sparing healthy cells from damage. However, this concept also requires rigorous testing and validation through clinical trials.
Could FOXO4-DRI be used for hair loss?
In summary, while the observed effects of FOXO4-DRI on fur density in mice are interesting, [4][6][13]it’s far from conclusive evidence that it could be a treatment for human hair loss. Hair loss is a complex issue with many contributing factors, and potential treatments need to be thoroughly researched and tested in humans before they can be considered safe and effective for this purpose.
Can FOXO4-DRI treats low testosterone?
It’s important to note that these findings are based on research conducted in animals and in vitro models, and the translation of such research to effective treatments in humans can be complex and challenging. Additionally,[2][6] the efficacy and safety of FOXO4-DRI for treating male late-onset hypogonadism would need to be rigorously tested in clinical trials before it could be considered a viable treatment option.
Storage FOXO4-DRI
FOXO4 D-Retro-Inverso(DRI) should be stored in a freezer at or below -9C. After reconstitution, FOXO4 D-Retro-Inverso(DRI) peptide should be kept refrigerated.
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Referenced Citations
[1]Parry P, Wei Y, Evans G (Feb 1995). “Cloning and characterization of the t(X;11) breakpoint from a leukemic cell line identify a new member of the forkhead gene family”. Genes Chromosomes Cancer. 11 (2): 79–84. doi:10.1002/gcc.2870110203. PMID 7529552. S2CID 19965473.
[2]Weigel D, Jäckle H (Nov 1990). “The fork head domain: a novel DNA binding motif of eukaryotic transcription factors?”. Cell. 63 (3): 455–456. doi:10.1016/0092-8674(90)90439-l. PMID 2225060. S2CID 1986657.
[3]van der Horst A, Burgering BM (Jun 2007). “Stressing the role of FoxO proteins in lifespan and disease”. Nature Reviews Molecular Cell Biology. 8 (6): 440–450. doi:10.1038/nrm2190. PMID 17522590. S2CID 31546098.
[4]Matsuzaki H, Daitoku H, Hatta M, Aoyama H, Yoshimochi K, Fukamizu A (Aug 2005). “Acetylation of Foxo1 alters its DNA-binding ability and sensitivityto phosphorylation”. Proceedings of the National Academy of Sciences of the United States of America. 102 (32): 11278–11283.Bibcode: 2005PNAS..10211278M. doi:10.1073/pnas.0502738102. PMC 1183558. PMID 16076959.
[5]Boura E, Silhan J, Herman P, Vecer J, Sulc M, Teisinger J, Obsilova V, Obsil T (Mar 2007). “Both the N-terminal loop and wing W2 of the forkhead domain of transcription factor Foxo4 are important for DNA binding”. The Journal of Biological Chemistry. 282 (11): 8265–8275. doi:10.1074/jbc.M605682200. PMID 17244620. S2CID 22561455.
[6]Neumann-Haefelin E, Qi W, Finkbeiner E, Walz G, Baumeister R, Hertweck M (Oct 2008). “SHC-1/p52Shc targets the insulin/IGF-1 and JNK signaling pathways to modulate life span and stress response in C. elegans”. Genes & Development. 22 (19): 2721–2735.
[7]Willcox BJ, Donlon TA, He Q, Chen R, Grove JS, Yano K, Masaki KH, Willcox DC, Rodriguez B, Curb JD (Sep 2008). “FOXO3A genotype is strongly associated with human longevity”. Proceedings of the National Academy of Sciences of the United States of America. 105 (37): 13987–13992. Bibcode:2008PNAS..10513987W. doi:10.1073/pnas.0801030105. PMC 2544566. PMID 18765803.
[8]Baar MP, Brandt RM, Putavet DA, Klein JD, Derks KW, Bourgeois BR, 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 RW, Madl T, Hoeijmakers JH, Campisi J, de Keizer PL (2017). “Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging”. Cell. 169 (1): 132–147. doi:10.1016/j.cell.2017.02.031. PMC 5556182. PMID 28340339.
[9]Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE (Apr 2004). “High frequency of mutations of the PIK3CA gene inhuman cancers”. Science. 304 (5670): 554. doi:10.1126/science.1096502. PMID 15016963. S2CID 10147415.
[10]Yang H, Zhao R, Yang HY, Lee MH (Mar 2005). “Constitutively active FOXO4 inhibits Akt activity, regulates p27 Kip1 stability, and suppresses HER2-mediated tumorigenicity”. Oncogene. 24 (11): 1924–35. doi:10.1038/sj.onc.1208352.PMID 15688030. S2CID 20360440.
[11]Liu X, Zhang Z, Sun L, Chai N, Tang S, Jin J, Hu H, Nie Y, Wang X, Wu K,Jin H, Fan D (Dec 2011). “MicroRNA-499-5p promotes cellular invasion and tumor metastasis in colorectal cancer by targeting FOXO4 and PDCD4”. Carcinogenesis. 32 (12): 1798–1805. doi:10.1093/carcin/bgr213. PMID 21934092.
[12]Liu X, Zhang Z, Sun L, Chai N, Tang S, Jin J, Hu H, Nie Y, Wang X, Wu K, Jin H, Fan D (Dec 2011). “MicroRNA-499-5p promotes cellular invasion and tumor metastasis in colorectal cancer by targeting FOXO4 and PDCD4”. Carcinogenesis. 32 (12): 1798–1805. doi:10.1093/carcin/bgr213. PMID 21934092.
[13]Brenkman AB, de Keizer PL, van den Broek NJ, van der Groep P, van Diest PJ, van der Horst A, Smits AM, Burgering BM (Sep 2008). “The peptidyl-isomerase Pin1 regulates p27kip1 expression through inhibition of Forkhead box O tumor suppressors”. Cancer Res. 68 (18): 7597–605. doi:10.1158/0008-5472.CAN-08-1059. PMID 18794148.
[14]Brenkman AB, de Keizer PL, van den Broek NJ, Jochemsen AG, Burgering BM (2008). Cookson MR (ed.).“Mdm2 induces mono-ubiquitination of FOXO4”. PLOS ONE. 3 (7): e2819. Bibcode:..3.2819B. doi:10.1371/journal.pone.0002819. PMC 2475507. PMID 18665269.
[15]Wong D, Yip S (April 2020).“Making heads or tails – the emergence of capicua (CIC) as an important multifunctional tumour suppressor”. The Journal of Pathology. 250 (5): 532–540. doi:1002/path.5400. PMID 32073140. S2CID 211192274.
Author of this article:
Dr. Jean Zeng graduated from king’s college london Faculty of Life Sciences & Medicine.Scientific Journal paper Author:
The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- TingtingLi
Reproductive Medicine Research Center, Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health & Science University, USA
Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA
In no way does this doctor/scientist endorse or advocate the purchase, sale, or use of this product for any reason. peptide.ltd has no affiliation or relationship, implied or otherwise, with this physician. The purpose of citing this doctor is to acknowledge, acknowledge and commend the exhaustive research and development work done by the scientists working on this peptide.
Author of this article:
Dr. Jean Zeng graduated from king's college london Faculty of Life Sciences & Medicine.
Scientific Journal paper Author:
Stephen C. Bain
Diabetes Research Group, Swansea University Medical School, Swansea, SA2 8PP, UK
Department of Diabetes and Endocrinology, Singleton Hospital, Swansea Bay University Health Board, Swansea, SA2 8QA, UK
In no way does this doctor/scientist endorse or advocate the purchase, sale, or use of this product for any reason. Polypeptide.ltd has no affiliation or relationship, implied or otherwise, with this physician. The purpose of citing this doctor is to acknowledge, acknowledge and commend the exhaustive research and development work done by the scientists working on this peptide.
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