Ingenol mebutate: a novel treatment for actinic keratosis

Collier, N.J.; Ali, Faisal; Lear, John T.

doi:10.2217/cpr.14.13

Cited by 11 publications

(12 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ingenol mebutate showed potent antiproliferative effects in a dose- and time-dependent manner against several cell lines [ 90 , 91 ], especially against colon 205 cells line with IC 50 = 10 nM, that means more active than staurosporine (IC 50 = 29 nM) or doxorubicin (IC 50 = 1.5 µM), known active compounds used as standards [ 90 ]. There is evidence that its effectiveness at damaging the tumor vasculature is related to the fact that it can be transported through the epidermis into the deep dermis via a P-glycoprotein [ 92 ]. Treatment with this compound, both in vitro (230 µM) and in vivo (42 nmol), rapidly caused swelling of mitochondria probably by loss of mitochondrial membrane potential and cell death by primary necrosis and is, therefore, unlikely to have its activity compromised by the development of apoptosis resistance in tumor cells [ 86 ].…”

Section: Secondary Metabolites From Plants As Anticancer Agentsmentioning

confidence: 99%

“…Unfortunately, adverse reactions associated with this application have been reported, although they are restricted to moderate “local skin responses” and included erythema, flaking/scaling, swelling, crusting, erosion/ulceration and vesiculation/postulation. However, it shows a favorable safety and tolerability profile exhibiting a lack of systemic absorption and photosensitivity [ 92 , 97 ].…”

Section: Secondary Metabolites From Plants As Anticancer Agentsmentioning

confidence: 99%

See 1 more Smart Citation

Plant Secondary Metabolites as Anticancer Agents: Successes in Clinical Trials and Therapeutic Application

Seca

Pinto

2018

IJMS

518

303

View full text Add to dashboard Cite

Cancer is a multistage process resulting in an uncontrolled and abrupt division of cells and is one of the leading causes of mortality. The cases reported and the predictions for the near future are unthinkable. Food and Drug Administration data showed that 40% of the approved molecules are natural compounds or inspired by them, from which, 74% are used in anticancer therapy. In fact, natural products are viewed as more biologically friendly, that is less toxic to normal cells. In this review, the most recent and successful cases of secondary metabolites, including alkaloid, diterpene, triterpene and polyphenolic type compounds, with great anticancer potential are discussed. Focusing on the ones that are in clinical trial development or already used in anticancer therapy, therefore successful cases such as paclitaxel and homoharringtonine (in clinical use), curcumin and ingenol mebutate (in clinical trials) will be addressed. Each compound’s natural source, the most important steps in their discovery, their therapeutic targets, as well as the main structural modifications that can improve anticancer properties will be discussed in order to show the role of plants as a source of effective and safe anticancer drugs.

show abstract

Section: Secondary Metabolites From Plants As Anticancer Agentsmentioning

confidence: 99%

Section: Secondary Metabolites From Plants As Anticancer Agentsmentioning

confidence: 99%

Plant Secondary Metabolites as Anticancer Agents: Successes in Clinical Trials and Therapeutic Application

Seca

Pinto

2018

IJMS

518

303

View full text Add to dashboard Cite

show abstract

“…Euphorbia peplus L., belonging to the Euphorbia genus of the Euphorbiaceae family, is indigenous to Europe and North Africa. Currently, it is distributed widely throughout the world and has been used as a folk medicine for many years in the treatment of skin lesions, inflammatory diseases, asthma, diabetes, and cancers. , Ingenol mebutate, an approved drug used for the treatment of actinic keratosis, was obtained from E. peplus . Previous phytochemical studies have revealed that jatrophane, ingenane, and pepluane diterpenoids are the main chemical constituents of E. peplus . − Jatrophane diterpenoids usually occur in the form of polyesters, possessing a 5/12 bicyclic pentadecane skeleton without a cyclopropane ring.…”

mentioning

confidence: 99%

Jatrophane Diterpenoids from Euphorbia peplus as Multidrug Resistance Modulators with Inhibitory Effects on the ATR-Chk-1 Pathway

et al. 2021

View full text Add to dashboard Cite

Twelve undescribed jatrophane diterpenoids, euphpepluones A−L (1−12), together with seven known analogues (13−19), were isolated from the whole plant of Euphorbia peplus, and their structures were elucidated by spectroscopic studies. The absolute configurations of 1 and 4 were assigned by X-ray crystallographic analysis. All isolates were investigated for their inhibitory effects against the ATR-Chk1 pathway using a Western blotting assay. As a result, 1, 2, 5, 8, 10, and 16 were found to suppress the camptothecin (CPT)-induced phosphorylation of Chk1, indicating that these compounds inhibit the activation of the ATR-Chk1 pathway. A preliminary structure−activity relationship (SAR) study of the isolates was conducted. When compound 10 and CPT were combined, apoptosis was induced in A549 cells with PARP cleavage, while there was no apoptotic effect by treatment with CPT or 10 alone. The data obtained indicate that 10 potentiates the chemotherapeutic sensitivity of A549 cells to CPT.

show abstract

“…To identify useful natural products, numerous isoprenoids are of significant commercial value owing to their broad-spectrum clinical and industrial applications (Tables 1 and 2). 19,[128][129][130][131][132][133][134][135][136][137][138][139][140][141][142][143][144][145] At present, the screening, isolation, and identification of new forms of natural compounds with pharmacological properties have gained increasing attention in academia and industry. In recent preclinical and clinical studies, the number of newly identified natural products with therapeutic efficacy in humans against diseases such as cancer, hepatitis, osteoporosis, and respiratory tract diseases has rapidly increased.…”

Section: Discussionmentioning

confidence: 99%

Structure, catalysis, and inhibition mechanism of prenyltransferase

Chang¹,

Cheng²,

Wang

2020

IUBMB Life

View full text Add to dashboard Cite

Isoprenoids, also known as terpenes or terpenoids, represent a large family of natural products composed of five-carbon isopentenyl diphosphate or its isomer dimethylallyl diphosphate as the building blocks. Isoprenoids are structurally and functionally diverse and include dolichols, steroid hormones, carotenoids, retinoids, aromatic metabolites, the isoprenoid side-chain of ubiquinone, and isoprenoid attached signaling proteins. Productions of isoprenoids are catalyzed by a group of enzymes known as prenyltransferases, such as farnesyltransferases, geranylgeranyltransferases, terpenoid cyclase, squalene synthase, aromatic prenyltransferase, and cis-and trans-prenyltransferases. Because these enzymes are key in cellular processes and metabolic pathways, they are expected to be potential targets in new drug discovery. In this review, six distinct subsets of characterized prenyltransferases are structurally and mechanistically classified, including (1) head-to-tail prenyl synthase, (2) head-to-head prenyl synthase, (3) head-tomiddle prenyl synthase, (4) terpenoid cyclase, (5) aromatic prenyltransferase, and (6) protein prenylation. Inhibitors of those enzymes for potential therapies against several diseases are discussed. Lastly, recent results on the structures of integral membrane enzyme, undecaprenyl pyrophosphate phosphatase, are also discussed.

show abstract

Ingenol mebutate: a novel treatment for actinic keratosis

Cited by 11 publications

References 53 publications

Plant Secondary Metabolites as Anticancer Agents: Successes in Clinical Trials and Therapeutic Application

Plant Secondary Metabolites as Anticancer Agents: Successes in Clinical Trials and Therapeutic Application

Jatrophane Diterpenoids from Euphorbia peplus as Multidrug Resistance Modulators with Inhibitory Effects on the ATR-Chk-1 Pathway

Structure, catalysis, and inhibition mechanism of prenyltransferase

Contact Info

Product

Resources

About