Phorbol 12-Myristate 13-acetate CAS NO.16561-29-8

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General tips：For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging：1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition：Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Chemical Properties of 12-O-tetradecanoylphorbol-13-acetate

Cas No.	16561-29-8
PubChem ID	27924	Appearance	White powder
Formula	C36H56O8	M.Wt	616.83
Type of Compound	Diterpenoids	Storage	Desiccate at -20°C
Synonyms	PMA
Solubility	Ethanol : 100 mg/mL (162.12 mM; Need ultrasonic) DMSO : ≥ 50 mg/mL (81.06 mM) H2O : < 0.1 mg/mL (insoluble) *"≥" means soluble, but saturation unknown.
SMILES	CCCCCCCCCCCCCC(=O)OC1C(C2(C(C=C(CC3(C2C=C(C3=O)C)O)CO)C4C1(C4(C)C)OC(=O)C)O)C
Standard InChIKey	PHEDXBVPIONUQT-RGYGYFBISA-N
General tips	For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging	1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment.
Shipping Condition	Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Source of 12-O-tetradecanoylphorbol-13-acetate

The seeds of Euphorbia lathyris L.

Biological Activity of 12-O-tetradecanoylphorbol-13-acetate

Description	1. 12-O-tetradecanoylphorbol-13-acetate has skin tumor-promoting potential. 2. 12-O-tetradecanoylphorbol-13-acetate induces endogenous FBXO10 mRNA and FBXO10 protein in Jurkat cells, a human T cell line. 3. 12-O-tetradecanoylphorbol-13-acetate provokes cell motility through regulating the expression and function of S100A14 in a KLF4-dependent manner.
Targets	PKC | AP-1

Preparing Stock Solutions of 12-O-tetradecanoylphorbol-13-acetate

	1 mg	5 mg	10 mg	20 mg	25 mg
1 mM	1.6212 mL	8.106 mL	16.2119 mL	32.4238 mL	40.5298 mL
5 mM	0.3242 mL	1.6212 mL	3.2424 mL	6.4848 mL	8.106 mL
10 mM	0.1621 mL	0.8106 mL	1.6212 mL	3.2424 mL	4.053 mL
50 mM	0.0324 mL	0.1621 mL	0.3242 mL	0.6485 mL	0.8106 mL
100 mM	0.0162 mL	0.0811 mL	0.1621 mL	0.3242 mL	0.4053 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

References on 12-O-tetradecanoylphorbol-13-acetate

Structure-dependent inhibitory effects of synthetic cannabinoids against 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and skin tumour promotion in mice.[Pubmed:23837590]

J Pharm Pharmacol. 2013 Aug;65(8):1223-30.

OBJECTIVES: Whether and how synthetic cannabinoids affect inflammation and carcinogenesis has not been well studied. The present study was thus conducted to assess effects of synthetic cannabinoids on inflammation and carcinogenesis in vivo in mice. METHODS: Twenty-three analogues of synthetic cannabinoids were isolated from, and identified as adulterants in, illegal drugs distributed in the Tokyo metropolitan area, and were examined for their inhibitory effects on the induction of oedema in mouse ears by 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, selected cannabinoids, JWH-018, -122 and -210, were studied for their effects on carcinogenesis induced in mouse skin initiated with 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by TPA. KEY FINDINGS: Among cannabinoids, naphthoylindoles mostly exhibited superior inhibitory effects against TPA-induced ear oedema and, especially, JWH-018, -122 and -210 showed potent activity with 50% inhibitory dose (ID50) values of 168, 346 and 542 nm, respectively (an activity corresponding to that of indometacin (ID50 = 908 nm)). Furthermore these three compounds also markedly suppressed the tumour-promoting activity of TPA. CONCLUSIONS: This is the first report indicating the structure-activity relationships for the anti-inflammatory activity of synthetic cannabinoids on TPA-induced inflammation in mice. Naphthoylindoles, JWH-018, -122 and -210, had the most potent anti-inflammatory activity and also markedly inhibited tumour promotion by TPA in the two-stage mouse skin carcinogenesis model. The present results suggest that synthetic cannabinoids, such as JWH-018, -122 and -210, may be used as cancer chemopreventive agents in the future.

Differential 12-O-Tetradecanoylphorbol-13-acetate-induced activation of rat mammary carcinoma susceptibility Fbxo10 variant promoters via a PKC-AP1 pathway.[Pubmed:24008983]

Mol Carcinog. 2015 Feb;54(2):134-47.

Rat mammary carcinoma susceptibility 5a1 (Mcs5a1), which is concordant to human MCS5A1 breast cancer risk locus, mediates susceptibility by a non-mammary cell-autonomous mechanism associated with T cell differential expression of F-box protein 10 (Fbxo10). Human FBXO10, an evolutionarily conserved ubiquitin ligase gene, was shown to have a potential role in regulating cell death by controlling the degradation of Bcl-2, a key protein involved in apoptosis. Breast cancer susceptibility is controlled by interactions between environmental and genetic factors; therefore, we sought to determine if breast cancer risk-associated environmental chemicals interact with Mcs5a1 variants using luciferase reporter constructs containing 4.2 kb Fbxo10 promoters based on alleles of mammary cancer susceptible Wistar Furth (WF) and resistant Wistar Kyoto (WKY) rat strains. 12-O-tetradecanoylphorbol-13-acetate (TPA) induced activation of a 4.2 kb WF Fbxo10 promoter region, but lower levels of activation of the homologous WKY Fbxo10 promoter region. Using general and specific protein kinase inhibitors, we identified a protein kinase C (PKC) pathway that mediated TPA activation. We narrowed the possible PKCs to a member of the atypical PKC isoforms, namely PKCmicro. We also determined that activator protein 1 (AP1) family member c-Fos mediated TPA activation of the 4.2 kb WF Fbxo10 promoter. TPA was shown to induce endogenous FBXO10 mRNA and FBXO10 protein in Jurkat cells, a human T cell line, with a maximal level of expression from 1.5 to 2.5 h after exposure. These results indicate that FBXO10/Fbxo10 expression is regulated by a PKC-dependent pathway acting through c-Fos, which binds AP1-specific DNA elements in Mcs5a1.

12-O-tetradecanoylphorbol-13-acetate promotes breast cancer cell motility by increasing S100A14 level in a Kruppel-like transcription factor 4 (KLF4)-dependent manner.[Pubmed:24532790]

J Biol Chem. 2014 Mar 28;289(13):9089-99.

The S100 protein family represents the largest subgroup of calcium binding EF-hand type proteins. These proteins have been reported to be involved in a wide range of biological functions that are related to normal cell development and tumorigenesis. S100A14 is a recently identified member of the S100 protein family and differentially expressed in a number of different human malignancies. However, the transcriptional regulation of S100A14 and its role in breast cancer needs to be further investigated. Here, we determined that 12-O-tetradecanoylphorbol-13-acetate (TPA) up-regulated the expression of KLF4 and facilitated its binding directly to two conserved GC-rich DNA segments within the S100A14 promoter, which is essential for the transactivation of KLF4 induced S100A14 expression. Furthermore, stable silencing of KLF4 significantly suppressed breast cancer cell migration induced by TPA. Collectively, these results offer insights into the fact that TPA provokes cell motility through regulating the expression and function of S100A14 in a KLF4-dependent manner.

Tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in an ultra-short-term skin carcinogenesis bioassay using rasH2 mice.[Pubmed:23610217]

Vet Pathol. 2013 Sep;50(5):903-8.

Assessment of the skin tumor-promoting potential of 12-O-tetradecanoylphorbol-13-acetate (TPA) after initiation with 7,12-dimethylbenz[a]anthracene (DMBA) was conducted using rasH2 transgenic (Tg) mice and their nontransgenic (non-Tg) littermates. Mice were treated with DMBA (50 mug/100 muL acetone) on clipped back skin at the commencement of the study, and 1 week thereafter, TPA was applied at 8 mug/200 muL or 4 mug/200 muL acetone, once or twice weekly, for 7 weeks. Skin nodules were observed in the rasH2 Tg mice from week 4, and the incidence reached 100% at weeks 5 and 6. The number of skin nodules (multiplicity) in the 8-mug twice-weekly, 8-mug once-weekly, 4-mug twice-weekly, and 4-mug once-weekly groups was 62.4, 46.2, 62.6, and 36.9, respectively. The non-Tg mice also developed skin nodules, but the sensitivity to induction in the rasH2 Tg mice was higher. No nodules were observed in the acetone groups, but single nodules were apparent in the no-treatment rasH2 Tg and non-Tg groups. In conclusion, skin promotion effects could be detected within only 8 weeks in the rasH2 mice, and the concentration of 4 mug TPA once weekly was sufficient as a positive control. This short-term skin carcinogenesis bioassay using rasH2 mice could represent a useful tool for the assessment of drug and chemical safety with cutaneous treatment.

Structural determinants of phorbol ester binding in synaptosomes: pharmacokinetics and pharmacodynamics.[Pubmed:10528137]

Eur J Pharmacol. 1999 Sep 17;381(1):77-84.

The present study used structurally distinct phorbol esters to investigate the relationship between their pharmacokinetics of binding to protein kinase C (PKC) in rat brain cortex synaptosomes, their affinity for PKC in synaptosomes and ability to enhance noradrenaline release from rat brain cortex. Affinity binding studies using [3deoxyphorbol 13-tetradecanoate (dPT)=PDB&z. Gt;12-deoxyphorbol 13-acetate (dPA)=phorbol 12,13-diacetate (PDA). In intact synaptosomes PDB, dPA and PDA rapidly displaced bound [3H]PDB whereas PMA and dPT were comparatively slow. However, the displacement rates for all the phorbol esters were equally rapid in synaptosomal membranes or synaptosomes permeabilised with Staphylococcus alpha-toxin. These results suggest that the lipophilic phorbol esters (dPT and PMA) are slower to displace [3H]PDB binding because they are hindered by the plasma membrane. In brain cortex slices it was found that the rate of displacement of [3H]PDB binding was closely correlated with the degree of elevation of transmitter noradrenaline release. Thus kinetic characteristics may determine biological responses and this may be particularly evident in events which occur rapidly or where there is fast counter-regulation.

A diacylglycerol analogue reduces neuronal calcium currents independently of protein kinase C activation.[Pubmed:2922062]

Nature. 1989 Mar 23;338(6213):340-2.

Diacylglycerol analogues (for example 1,2-oleoylacetylglycerol, OAG) and phorbol esters are activators of protein kinase C, and have been widely used to study the function of this enzyme in both intact cells and cell-free preparations. Electrophysiological studies have shown that these activators can either depress or increase Ca2+ currents, or decrease K+ currents when applied outside the cell. It has been assumed that these effects are mediated by protein kinase C activation. Here we report that micromolar levels of OAG and phorbol esters depress Ca2+ currents in chick sensory neurons independently of their effect as activators of protein kinase C. The depression of the Ca2+ current is rapid and is unaffected by intracellular application of the protein kinase C inhibitors staurosporin, sphingosine and H-7. Furthermore, the activators were ineffective when applied intracellularly, indicating that their site of action is on the outside of the membrane.

Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters.[Pubmed:7085651]

J Biol Chem. 1982 Jul 10;257(13):7847-51.

Tumor-promoting phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) directly activate in vitro Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C), which normally requires unsaturated diacylglycerol. Kinetic analysis indicates that TPA can substitute for diacylglycerol and greatly increases the affinity of the enzyme for Ca2+ as well as for phospholipid. Under physiological conditions, the activation of this enzyme appears to be linked to the receptor-mediated phosphatidylinositol breakdown which may be provoked by a wide variety of extracellular messengers, eventually leading to the activation of specific cellular functions or proliferation. Using human platelets as a model system, TPA is shown to enhance the protein kinase C-specific phosphorylation associated with the release reaction in the total absence of phosphatidylinositol breakdown. Various phorbol derivatives which have been shown to be active in tumor promotion are also capable of activating this protein kinase in in vitro systems.

Description

Phorbol 12-myristate 13-acetate (PMA), a phorbol ester, is a dual SphK and protein kinase C (PKC) activator.

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