U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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Status:
Investigational
Source:
NCT02205892: Not Applicable Interventional Completed Acne
(2014)
Source URL:

Class (Stereo):
CHEMICAL (ABSOLUTE)



Lupeol, a biologically active dietary triterpenoid, is found in many medicinal plants and different fruits such as olives, mangos, and strawberries. Lupeol exhibits a wide spectrum of pharmacological properties including anti-inflammatory, anti-cancer, anti-diabetic, anti-microbial, cardioprotective, and hepatoprotective activities. Lupeol inhibits LPS-induced microglial neuroinflammation via the P38-MAPK and JNK pathways and has therapeutic potential to treat various neuroinflammatory disorders. Lupeol possesses antiskin tumor-promoting effects in CD-1 mouse and inhibits conventional as well as novel biomarkers of tumor promotion. It strongly suppressed lipogenesis by modulating the IGF-1R/phosphatidylinositide 3 kinase (PI3K)/Akt/sterol response element-binding protein-1 (SREBP-1) signaling pathway in SEB-1 sebocytes, and reduced inflammation by suppressing the NF-κB pathway in SEB-1 sebocytes and HaCaT keratinocytes. Lupeol exhibited a marginal effect on cell viability and may have modulated dyskeratosis of the epidermis. These results demonstrate the clinical feasibility of applying lupeol for the treatment of acne.
5F-DF-203-L-LYSINAMIDE (Phortress) is an experimental antitumor agent with potent and selective activity against human-derived carcinomas of breast, ovarian and renal origin. The mechanism of action of Phortress is distinct from all classes of chemotherapeutic agents currently in the clinic, and involves metabolic activation by cytochrome P450 (CYP) 1A1 to electrophilic species, which generate DNA adducts in sensitive tumors only. Phortress is in phase I clinical trials for the treatment of solid tumours. The compound was co-developed by Pharminox, University of Nottingham and Cancer Research UK.
Eleutheroside E is one of the active constituents of the Eleutherococcus senticosus (Rupr. & Maxim.) is also called Harms (ES), Acanthopanax senticosus, Siberian ginseng, or Gasiogapi in Korea. It is a diastereoisomer of Eleutheroside D. Eleutheroside E (EE) significantly decreased the inflammatory cell infiltration, pannus formation, cartilage damage, and bone erosion of collagen-induced arthritis mice, highlighting Eleutheroside E as a potential therapeutic agent for rheumatoid arthritis. Treatment of rat mesangial cells with Eleutheroside E markedly attenuated high glucose induced cells proliferation and in a dose-dependent manner. Intervention with EE also significantly blocked high glucose induced intracellular ROS production by decreasing NADPH oxidase activity. Intervention with EE also significantly blocked high glucose induced intracellular ROS production by decreasing NADPH oxidase activity. EE mediates the hyperglycemic effects of Eleutherococcus senticosus by regulating insulin signaling and glucose utilization. The beneficial effects of EE may provide an effective and powerful strategy to alleviate diabetes. Eleutheroside E exhibited weak inhibition against CYP2C9, CYP2E1 activity, and no effect on CYP2D6 and CYP3A4. The inhibition can result in the increase of the plasma concentration and toxicity of concomitant drugs, especially for those with narrow therapeutic windows such as warfarin, phenobarbital and phenytoin.
10-Hydroxy-2-decenoic acid, a natural fatty acid that has been extracted from royal jelly obtained from honeybees (Apis mellifera) and exhibits estrogenic action. 10-hydroxy-2-decenoic(10-HDA)dose-dependently inhibited the formation of the gastric ulcer induced by stress, pyloric ligation, and indomethacin selectively in rats. 10-HDA also accelerated the healing of gastric ulcer induced by acetic acid, by which the gastric acid output was decreased in a dose-dependent manner. A mechanism putatively linked to 10-HDA anti-inflammatory effect is the inhibition of LPS-induced NF-kB activation observed in the murine macrophage cell line RAW264. 10-HDA and 4-hydroperoxy-2-decenoic acid ethyl ester have been shown to inhibit histone deacetylase activity, thereby enhancing the expression of extracellular SOD release by leukemia THP-1 cells, and suggesting therapeutic potential against atherosclerosis. Various immunomodulatory activities have been reported for 10-HDA, including reduced T cell proliferation, inhibition of interleukin-12 production by spleen dendritic cells, and blocks of LPS- and IFN-b-induced NO production in macrophages. 10-HDA has been shown to increase collagen synthesis and production of the collagen promoting factor, transforming growth factor b1, in human skin fibroblasts. Such an effect is thought to mediate royal jelly skin protection against UVB-induced photoaging. 10-HDA and 10-hydroxydecanoic acid have been shown to act as potent agonists of the human TRPA1 and TRPV1 receptors. 10-HDA has stimulated neuron differentiation from rat embryo neural stem cells, possibly acting like the omega-3 docosahexaenoic acid, an essential diet component that is known to promote neurogenesis in the central nervous system.
Methylinositol is a natural product in the family of inositols. It is found in many foods as well as pine tree bark. Methylinositol is found naturally in many foods and is commercially available as an approved food supplement. Methylinositol can mediate insulin action to improve glycemic control and insulin sensitivity in patients with type 2 diabetes mellitus, especially in patients with insulin resistance. It plays a positive role in regulating insulin-mediated glucose uptake in the liver through translocation and activation of the PI3K/Akt signaling pathway. The compound also modulates gamma-secretase to reduce A-betta production while sparing cleavage of the gamma-secretase substrate Notch. Methylinositol improves cognitive function and memory deficits in preclinical models of Alzheimer's disease (AD) neuropathology. Methylinositol was will tolerated in the population of AD subjects of varying age and severity. No serious adverse effects were detected in clinical trials. Many plant-derived compounds have excellent therapeutic potential against various human ailments. It was shown, that methylinositol mitigates tumor growth by modulating interleukins and hormones and induces apoptosis in rat breast carcinogenesis through inhibition of NF-κB.
Zingerone is one of the active phenolic components isolated from Zingiber officinale. Zingerone is primarily present in dry ginger, but cooking or drying also converts gingerol into zingerone by a retroaldol reaction. Chemically synthesized zingerone is vanillyl acetone, which is a member of the phenolic alkanone group, and its varied pharmacological properties include antioxidant, anti-inflammatory, and anticancer activities. Thus, zingeroneshowed strong anti-angiogenic activity via the inhibition of MMP-2 and MMP-9 during tumor progression. Zingerone was likely to be broad-spectrum anti-inflammatory agents in most organs that suppressed the activation of NF-κB, the production of IL-1β, and the infiltration of inflammatory cells in mice. Zingerone effectively inhibits 1,2-dimethylhydrazine-induced colon carcinogenesis in male Wistar rats. Zingerone possess radioprotective effects in laboratory animals and in cultured cells in vitro. Zingerone produced marked improvement in stress induced irritable bowel disorder, which could be attributed to the powerful antioxidant nature, direct effect on the intestinal smooth muscle and adaptogenic nature. Analysis of the qualities that constituted zingerone irritation found that the sensations produced are predominantly burning and warmth, making it qualitatively similar to capsaicin.
5F-DF-203-L-LYSINAMIDE (Phortress) is an experimental antitumor agent with potent and selective activity against human-derived carcinomas of breast, ovarian and renal origin. The mechanism of action of Phortress is distinct from all classes of chemotherapeutic agents currently in the clinic, and involves metabolic activation by cytochrome P450 (CYP) 1A1 to electrophilic species, which generate DNA adducts in sensitive tumors only. Phortress is in phase I clinical trials for the treatment of solid tumours. The compound was co-developed by Pharminox, University of Nottingham and Cancer Research UK.
5F-DF-203-L-LYSINAMIDE (Phortress) is an experimental antitumor agent with potent and selective activity against human-derived carcinomas of breast, ovarian and renal origin. The mechanism of action of Phortress is distinct from all classes of chemotherapeutic agents currently in the clinic, and involves metabolic activation by cytochrome P450 (CYP) 1A1 to electrophilic species, which generate DNA adducts in sensitive tumors only. Phortress is in phase I clinical trials for the treatment of solid tumours. The compound was co-developed by Pharminox, University of Nottingham and Cancer Research UK.
Methylinositol is a natural product in the family of inositols. It is found in many foods as well as pine tree bark. Methylinositol is found naturally in many foods and is commercially available as an approved food supplement. Methylinositol can mediate insulin action to improve glycemic control and insulin sensitivity in patients with type 2 diabetes mellitus, especially in patients with insulin resistance. It plays a positive role in regulating insulin-mediated glucose uptake in the liver through translocation and activation of the PI3K/Akt signaling pathway. The compound also modulates gamma-secretase to reduce A-betta production while sparing cleavage of the gamma-secretase substrate Notch. Methylinositol improves cognitive function and memory deficits in preclinical models of Alzheimer's disease (AD) neuropathology. Methylinositol was will tolerated in the population of AD subjects of varying age and severity. No serious adverse effects were detected in clinical trials. Many plant-derived compounds have excellent therapeutic potential against various human ailments. It was shown, that methylinositol mitigates tumor growth by modulating interleukins and hormones and induces apoptosis in rat breast carcinogenesis through inhibition of NF-κB.