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Chemical Structure| 16561-29-8 Chemical Structure| 16561-29-8
Chemical Structure| 16561-29-8

*Storage: Keep in dark place,Inert atmosphere,Store in freezer, under -20°C.

Phorbol 12-myristate 13-acetate

CAS No.: 16561-29-8

Phorbol 12-myristate 13-acetate is a PKC-activating phorbol ester, increases the intracellular Ca2+ concentration ([Ca2+]i) in a dose-dependent manner, with an EC50 of 11.7 nM.

Synonyms: PMA;TPA;Phorbol myristate acetate

4.5 *For Research Use Only !

Cat. No.: A175370 Purity: 95%

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Product Citations

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Zhang, Haoran ; Nie, Jinlin ; Bao, Zhen , et al.

Abstract: Colorectal cancer is a highly prevalent and deadly malignancy worldwide. Current treatment strategies, including surgery, chemotherapy, and targeted therapy, still face limitations due to recurrence and metastasis. By conducting a weighted gene coexpression network analysis on gene expression data from The Cancer Genome Atlas, we pinpointed critical genes linked to M2 macrophages and tumor metastasis. Among these, FOXC1 emerged as a significant prognostic indicator within our predictive model. Clinical sample analysis further confirmed that FOXC1 is upregulated in colorectal cancer tissues and associated with an unfavorable patient outcome. Both in vivo and in vitro experimental results revealed that FOXC1 promotes CRC cell migration, invasion and proliferation by regulating the expression of Snail and TGF-β/Smad2/3 pathways, thereby facilitating the epithelial–mesenchymal transition process. Additionally, FOXC1 recruits M2 macrophages to the tumor microenvironment by regulating CXCL2 expression through Snail. The TGF-β factor secreted by M2 macrophages further activates the TGF-β/Smad2/3 pathway, forming a positive feedback loop. In these processes, FOXC1 plays a critical regulatory role. In summary, this study highlights the critical significance of FOXC1 in CRC progression and indicates its viability as a therapeutic target, offering a novel theoretical foundation for the development of future CRC treatment strategies.

Keywords: Colorectal cancer ; WGCNA ; FOXC1 ; Epithelial–mesenchymal transition ; TGF-β/Smad2/3 signalling pathway ; Macrophages

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Keeney, Justin N. ; Winters, Ashley D. ; Sitcheran, Raquel , et al.

Abstract: NF-kB-inducing kinase (NIK), which is essential for the activation of the noncanonical NF-kB pathway, regulates diverse processes in immunity, development, and disease. Although recent studies have elucidated important functions of NIK in adaptive immune cells and cancer cell metabolism, the role of NIK in metabolic-driven inflammatory responses in innate immune cells remains unclear. In this study, we demonstrate that murine NIK-deficient bone marrow derived macrophages exhibit defects in mitochondrial-dependent metabolism and oxidative phosphorylation, which impair the acquisition of a prorepair, anti-inflammatory phenotype. Subsequently, NIK-deficient mice exhibit skewing of myeloid cells characterized by aberrant eosinophil, monocyte, and macrophage cell populations in the blood, bone marrow, and adipose tissue. Furthermore, NIK-deficient blood monocytes display hyperresponsiveness to bacterial LPS and elevated TNF-α production ex vivo. These findings suggest that NIK governs metabolic rewiring, which is critical for balancing proinflammatory and anti-inflammatory myeloid immune cell function. Overall, our work highlights a previously unrecognized role for NIK as a mol. rheostat that fine-tunes immunometabolism in innate immunity, and suggests that metabolic dysfunction may be an important driver of inflammatory diseases caused by aberrant NIK expression or activity.

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Product Details of [ Phorbol 12-myristate 13-acetate ]

CAS No. :16561-29-8
Formula : C36H56O8
M.W : 616.83
SMILES Code : CCCCCCCCCCCCCC(O[C@H]([C@H]1C)[C@]2(OC(C)=O)[C@@]([C@@](C=C(CO)C[C@]34O)([H])[C@@]1(O)[C@]4([H])C=C(C)C3=O)([H])C2(C)C)=O
Synonyms :
PMA;TPA;Phorbol myristate acetate
MDL No. :MFCD00036736
InChI Key :PHEDXBVPIONUQT-RGYGYFBISA-N
Pubchem ID :27924

Safety of [ Phorbol 12-myristate 13-acetate ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H314-H317-H334-H351-H300+H310+H330
Precautionary Statements:P201-P202-P262-P264-P270-P271-P272-P280-P284-P303+P361+P353-P304+P340-P305+P351+P338-P310-P330-P331-P363-P403+P233-P405-P501
Class:6.1(8)
UN#:2928
Packing Group:

Biological Activity

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT01195272 Rheumatoid Arthritis Phase 4 Completed - United Kingdom ... More >> Liverpool, United Kingdom, L9 7AL Less <<
NCT01195272 - Completed - -
NCT02137876 - Withdrawn(Subject recruitment ... More >>was unsuccessful.) Less << - United States, Illinois ... More >> Northwestern University Comprehensive Transplant Center Chicago, Illinois, United States, 60611 Less <<
NCT00551746 Cardiovascular Disease Not Applicable Completed - United States, Utah ... More >> Intermountain Medical Center Murray, Utah, United States, 84157 Less <<
NCT03448250 Breast Cancer Not Applicable Recruiting March 2020 Germany ... More >> Technical University of Dortmund, Leibniz Research Centre for Working Environment and Human Factors Recruiting Dortmund, Germany, 44139 Contact: Carsten Watzl, PhD    +492311084233    watzl@ifado.de    University Medical Center Leipzig, Department of Medical Psychology and Medical Sociology, Section Psychosocial Oncology Active, not recruiting Leipzig, Germany, 04103 Less <<
NCT00551746 - Completed - -
NCT00364715 - Completed - Taiwan ... More >> National Taiwan University Hospital Taipei, Taiwan, 100 Less <<
NCT01795924 Acute Myelogenous Leukemia|Mye... More >>lodysplastic Syndrome Less << PHASE1|PHASE2 TERMINATED 2025-11-14 City of Hope, Duarte, Californ... More >>ia, 91010, United States|University of Kentucky Medical Center, Lexington, Kentucky, 40513, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.62mL

0.32mL

0.16mL

8.11mL

1.62mL

0.81mL

16.21mL

3.24mL

1.62mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

[1]Mugami S, Kravchook S, et al. Differential roles of PKC isoforms (PKCs) and Ca(2+) in GnRH and phorbol 12-myristate 13-acetate(PMA) stimulation of p38MAPK phosphorylation in immortalized gonadotrope cells. Mol Cell Endocrinol. 2017 Jan 5;439:141-154.

[2]Xu F, Satoh E, et al. Protein kinase C-mediated Ca2+ entry in HEK 293 cells transiently expressing human TRPV4. Br J Pharmacol. 2003 Sep;140(2):413-21. Epub 2003 Aug 11.

[3]Blumberg PM. Protein kinase C as the receptor for the phorbol ester tumor promoters: sixth Rhoads memorial award lecture. Cancer Res. 1988 Jan 1;48(1):1-8.

[4]Kawasaki H, Springett GM, Toki S, Canales JJ, Harlan P, Blumenstiel JP, Chen EJ, Bany IA, Mochizuki N, Ashbacher A, Matsuda M, Housman DE, Graybiel AM. A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia. Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13278-83.

[5]Jiang Y, Fleet JC. Effect of phorbol 12-myristate 13-acetate activated signaling pathways on 1α, 25 dihydroxyvitamin D3 regulated human 25-hydroxyvitamin D3 24-hydroxylase gene expression in differentiated Caco-2 cells. J Cell Biochem. 2012 May;113(5):1599-607.

[6]Gordon JR, Galli SJ. Phorbol 12-myristate 13-acetate-induced development of functionally active mast cells in W/Wv but not Sl/Sld genetically mast cell-deficient mice. Blood. 1990 Apr 15;75(8):1637-45.

[7]Hurley JH, Newton AC, Parker PJ, Blumberg PM, Nishizuka Y. Taxonomy and function of C1 protein kinase C homology domains. Protein Sci. 1997 Feb;6(2):477-80.

[8]De Vry CG, Valdez M, Lazarov M, et al. Topical application of a novel immunomodulatory peptide, RDP58, reduces skin inflammation in the phorbol ester-induced dermatitis model. J Invest Dermatol. 2005;125(3):473-481.

 

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