Prostratin

Activation of latent reservoirs of HIV-infected cells is a treatment strategy designed to reduce viral load and eliminate the perpetuation of retroviral infection. Prostratin is a non-tumor promoting phorbol ester that potently induces HIV-1 reactivation in latent reservoirs of infected Jurkat-LAT-GFP cells with an IC₅₀ value of ~0.5 µM.¹ Originally, prostratin was isolated from plant sources including P. prostrata, E. cornigera, and H. nutans. ² The effects of prostratin are mediated through activation of NF-κB via protein kinase C and by downregulation of HIV-1 receptor CD4 expression and its co-receptors CXCR4 and CCR5.^3,4,5

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1. Bedoya, L.M., Márquez, N., Martínez, N., et al. SJ23B, a jatrophane diterpene activates classical PKCs and displays strong activity against HIV in vivo. Biochem. Pharmacol. 77(6), 965-978 (2009).

2. Wender, P.A., Kee, J.M., and Warrington, J.M. Practical synthesis of prostratin, DPP, and their analogs, adjuvant leads against latent HIV. Science 320(5876), 649-652 (2008).

3. Williams, S.A., Chen, L.F., Kwon, H., et al. Prostratin antagonizes HIV latency by activating NF-ĸB. The Journal of Biological Chemisty 279(40), 42008-42017 (2004).

4. Biancotto, A., Grivel, J.C., Gondois-Rey, F., et al. Dual role of prostratin in inhibition of infection and reactivation of human immunodeficiency virus from latency in primary blood lymphocytes and lymphoid tissue. J. Virol. 78(19), 10507-10515 (2004).

5. Hezareh, M., Moukil, M.A., Szanto, I., et al. Mechanisms of HIV receptor and co-receptor down-regulation by prostratin: Role of conventional and novel PKC isoforms. Antivir. Chem. Chemother. 15(4), 207-222 (2004).