Prostratin
(Synonyms: 13-O-乙酰基-12-脱氧佛波醇,13-O-Acetylphorbol) 目录号 : GC44729An HIV re-activator
Cas No.:60857-08-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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]
Reference:
[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. Biochemical Pharmacology 77, 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, 649-652 (2008).
[3]. Williams, S.A., Chen, L.F., Kwon, H., et al. Prostratin antagonizes HIV latency by activating NF- k B. 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. Journal of Virology 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, 207-222 (2004).
| Cas No. | 60857-08-1 | SDF | |
| 别名 | 13-O-乙酰基-12-脱氧佛波醇,13-O-Acetylphorbol | ||
| 化学名 | 9a-(acetyloxy)-1,1aR,1bS,4,4aR,7aS,7bR,8R,9,9aS-decahydro-4a,7b-dihydro-3-(hydroxymethyl)-1,1,6,8-tetramethyl-5H-cyclopropa[3,4]benz[1,2-e]azulen-5-one | ||
| Canonical SMILES | OCC1=C[C@H]2[C@H]3[C@@](OC(=O)C)(C[C@@H](C)C2(O)C2C=C(C)C(=O)[C@@]2(O)C1)C3(C)C | ||
| 分子式 | C22H30O6 | 分子量 | 390.5 |
| 溶解度 | 10mg/mL in DMSO,10mg/mL in DMF, 10mg/mL in Ethanol | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5608 mL | 12.8041 mL | 25.6082 mL |
| 5 mM | 0.5122 mL | 2.5608 mL | 5.1216 mL |
| 10 mM | 0.2561 mL | 1.2804 mL | 2.5608 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Prostratin: An Overview
Mini Rev Med Chem 2015;15(13):1122-30.PMID:25963564DOI:10.2174/1389557515666150511154108.
Terpenoid class of molecules possesses a diverse therapeutic properties and potentials owing to their specific structural features. Prostratin and its derivatives are exemplified in this context to exhibit a variety of biological activities. In this review we discuss in detail the role of Prostratin as potential therapeutic and underlying molecular mechanisms by which it accomplishes these activities. Prostratin [13-O-acetyl-12-deoxyphorbol] is a phorbol ester that was first isolated from Strathmore weed Pimelea prostrate, a small endemic New Zealand shrub, and characterized by Hecker in 1976. Structurally, Prostratin contains four rings designated as A, B, C and D. Ring A is trans linked to the 7-membered ring B while Ring C is a 6 membered and is cis linked to the cyclopentane ring D. Chemical synthesis of this compound initiated with acidic hydrolysis of phorbol, a tigliane diterpene isolated from croton oil. Prostratin-containing extracts have been used by the Samoan healers to treat individuals with certain medical conditions such as jaundice. Importantly, these treatments are not associated with any significant side effect. Prostratin inhibits HIV-1 infections by down regulating HIV-1 cellular receptors through the activation of protein kinase C (PKC) pathway and reduces the HIV-1 latency. Unlike other phorbol esters that induce carcinogenesis by activating PKC, Prostratin does not induce tumors rather has shown tumor suppressing activity. Its ability to induce lytic gene expression supports a role for phorbol-ester regulated signaling pathways in Kaposi's sarcoma associated herpes-virus reactivation.
Prostratin as a new therapeutic agent targeting HIV viral reservoirs
Drug News Perspect 2005 Oct;18(8):496-500.PMID:16391719DOI:10.1358/dnp.2005.18.8.944543.
The persistence of latent reservoirs of human immunodeficiency virus type 1 (HIV-1) represents a major barrier to virus eradication in patients on combination antiretroviral therapy. It has been suggested that treating infected individuals simultaneously with highly active antiretroviral therapy (HAART) and agents that activate cells to express HIV-1 might eliminate these latent reservoirs. The phorbol ester Prostratin, used in Western Samoa as an ethno-botanical treatment for viral hepatitis, was isolated at the National Cancer Institute in 1992. Prostratin represents a distinct subclass of protein kinase C activators, since unlike other phorbol esters it does not induce tumor formation. Prostratin upregulates expression of viral products from latently infected cells such as U1, ACH-2 and peripheral blood mononuclear cells from patients on HAART with undetectable plasma viremia. It also inhibits HIV infection and viral spread at the entry/fusion step of viral life cycle. The lack of tumor promotion of Prostratin coupled with its ability to upregulate latent HIV-1 provirus expression and inhibition of viral infection are important features that could be exploited as effective therapy to eliminate latent reservoirs.
Potential anticancer effect of Prostratin through SIK3 inhibition
Oncol Lett 2018 Mar;15(3):3252-3258.PMID:29435066DOI:10.3892/ol.2017.7674.
Prostratin, a phorbol ester natural plant compound, has been demonstrated to exert an anti-retroviral effect through activation of latent cluster of differentiation (CD)4+T lymphocytes and inhibition of viral entry into the cell through downregulation of chemokine receptor type 4 (CXCR4) expression. However, the potential effect of Prostratin on cancer is yet to be defined. As CXCR4 is well known to induce cancer migration, it was hypothesized that Prostratin induces an anti-cancer effect through inhibition of CXCR4 expression. The authors previously demonstrated that high stimulating conditions (sub-minimal IL-17, 0.1 ng/ml, synergized with high salt, Δ0.05 M NaCl) promote breast cancer cell proliferation and CXCR4 expression through upregulation of salt-inducible kinase (SIK)-3. The present study demonstrated that Prostratin selectively exerted increased cytotoxicity (IC50 of 7 µM) when breast cancer cells were cultured in high stimulating conditions, compared with regular basal culture conditions (IC50 of 35 µM). Furthermore, the cytotoxic potential of Prostratin was increased seven-fold in the four breast cancer cell lines (MCF-7, MDA-MB-231, BT-20 and AU-565) compared with the non-malignant MCF10A breast epithelial cell line. This suggested that Prostratin specifically targets cancer cells over normal cells. Mechanistic studies revealed that Prostratin inhibited CXCR4 expression in breast cancer cells through downregulation of SIK3 expression. Overall, the data suggest that Prostratin is a novel drug target for the pro-oncogenic factor SIK3. These studies could form a basis for further research to evaluate the anticancer effect of Prostratin in a combinatorial chemotherapeutic regimen.
Prostratin exhibits both replication enhancing and inhibiting effects on FIV infection of feline CD4+ T-cells
Virus Res 2013 Jan;171(1):121-8.PMID:23201205DOI:10.1016/j.virusres.2012.11.004.
The phorbol ester Prostratin may either stimulate or inhibit human immunodeficiency virus-1 (HIV-1) replication. Here we report that Prostratin also exhibits a similar dual action upon feline immunodeficiency virus (FIV) replication in an IL-2-dependent feline CD4(+) T-cell line (MYA-1). While withdrawal of IL-2 halted FIV spread, Prostratin rescued virus production and cell viability, mimicking the functions of the cytokine. Conversely, FIV grew rapidly in the presence of IL-2 and this was inhibited by Prostratin. In contrast to HIV-1, Prostratin mediated inhibition of FIV through means other than blocking virus entry. Co-application of the protein kinase C (PKC) inhibitor Gö6850 with Prostratin reversed both the inhibitory and stimulatory effects, suggesting that PKC is crucial for FIV replication.
Prostratin induces HIV activation and downregulates HIV receptors in peripheral blood lymphocytes
Antivir Ther 2004 Aug;9(4):545-54.PMID:15456086doi
Induction of HIV expression through lymphocyte activation has been proposed as a strategy to purge latent reservoirs. Prostratin is a non-tumourogenic phorbol ester that delays HIV replication in vitro, but paradoxically activates HIV expression in latently infected cells. To get a better insight into the mechanisms of action of Prostratin, we have analysed the effect of Prostratin on HIV activation and HIV receptor and coreceptors' surface expression in human lymphocytes. Peripheral blood mononuclear cells (PBMCs) were transfected with luciferase expression constructs under the control of wild type HIV-long terminal repeat (LTR) and consensus sequences for transcription factors involved in HIV-LTR transactivation (NF-kappaB, SP1, NFAT). Prostratin stimulates transactivation of LTR vectors, kappaB- and SP-1-driven luciferase constructs. In another set of experiments, PBMCs were transfected with a full-length infectious viral clone. Prostratin induced HIV transcription and viral expression as detected by luciferase activity in cellular extracts and p24 levels in culture supernatants, respectively. Expression of the HIV coreceptors CCR5 and CXCR4 was decreased by Prostratin and, concomitantly, Prostratin inhibited the infection of PBMCs with R5 and X4 strains. However, Prostratin did not inhibit infection with a pseudotyped viral clone that enters into the cells independently of HIV receptors. These results help to explain the paradoxical effects of Prostratin. On one hand, Prostratin induces HIV activation in latently infected cells through the induction of NF-kappaB and Sp1. On the other hand, strong and persistent downregulation of HIV receptors decreases infection of new targets and delays HIV propagation. These data support the potential use of Prostratin to activate HIV from latency and purge viral reservoirs.