phorbol 12-myristate

Phorbol 12-myristate 13-acetate (PMA) belongs to the phorbol ester group of natural products and is an activator of PKC, SphK, and NF-κB. Phorbol 12-myristate 13-acetate induces THP1 cell differentiation.

(Rac)-Phorbol-12-(2-methylbutyrate), a natural product, can be isolated from croton oil [1].

Phorbol 12-tiglate, a derivative of Phorbol, which in turn is a hydrolyzed product of Croton oil, plays a role in tumor promotion through activation of protein kinase C. This compound and its related derivatives are employed in the construction of carcinogenic models for biomedical research [1].

Beta-Tocopherol shows effect on human erythroleukemia cell (HEL) adhesion induced by phorbol 12-myristate 13-acetate (PMA).

Lyso-globotriaosylceramide is a form of globotriaosylceramide that is lacking the fatty acyl group. It binds to Shiga toxin 1 (Stx1) in the presence of cholesterol and phosphatidylcholine but does not bind Stx2. It also reduces viability and aggregation of human neutrophils induced by phorbol 12-myristate 13-acetate when used at concentrations of 50 and 1 μM, respectively. Lyso-globotriaosylceramide accumulates in the brain, heart, kidney, liver, lung, and spleen in a mouse model of Fabry disease, a lysosomal storage disorder characterized by a deficiency in the enzyme α-galactosidase A. It also accumulates in the urine, kidney, and plasma of patients with Fabry disease. Lyso-globotriaosylceramide levels decrease in response to administration of the α-galactosidase inhibitor 1-deoxygalactonojirimycin in a transgenic mouse model of Fabry disease. Decreases in plasma and urine concentrations of lyso-globotriaosylceramide have been used as a biomarker for efficacy of enzyme replacement therapy (ERT) and other therapies in the treatment of Fabry disease.

Sphingosine (d14:1) is a bioactive sphingolipid that has been found in B. mori (silkworm), P. clarkii (crayfish), and A. aurita (jellyfish) extracts. It increases the germination rate of N. rileyi, an entomopathogenic fungus, with an EC50 value of 10.2 nM. Sphingosine (d14:1) inhibits protein kinase C (PKC) in vitro (IC50 = 7.3 mol%) as well as superoxide generation induced by phorbol 12-myristate 13-acetate in neutrophils and reduces growth of CHO cells (IC50s = 19 and 8 μM, respectively).

Gliovirin is a fungal metabolite that has been found inT. harzianumand has fungicidal, antimicrobial and anti-inflammatory activities.1It is active against the plant pathogenic fungusP. ultimum(MIC = 60 ng/ml) and the parasiteT. brucei brucei(IC50= 90 ng/ml), but has no effect on the plant pathogenic fungiR. solani,P. omnivorum,T. basicola,R. arrhizus, andV. dahliaeor the bacteriaB. thuringiensis,P. fluorescens, andX. malvacearumwhen used at concentrations up to 1,000 ng/ml.2,3Gliovirin decreases phorbol 12-myristate 13-acetate (TPA)- and ionomycin-induced increased expression of COX-2 (IC50= 1 μM) and protein levels of IL-2 in Jurkat cells (IC50= 5.2 μM).1 1.Rether, J., Serwe, A., Anke, T., et al.Inhibition of inducible tumor necrosis factor-α expression by the fungal epipolythiodiketopiperazine gliovirinBiol. Chem.388(6)627-637(2007) 2.Howell, C.R., and Stipanovic, R.D.Gliovirin, a new antibiotic from Gliocladium virens, and its role in the biological control of Pythium ultimumCan. J. Microbiol.29(3)321-324(1983) 3.Iwatsuki, M., Otoguro, K., Ishiyama, A., et al.In vitro antitrypanosomal activity of 12 low-molecular-weight antibiotics and observations of structure/activity relationshipsJ. Antibiot. (Tokyo)63(10)619-622(2010)