Ingenol Mebutate: A Promising Treatment for Actinic Keratoses and Nonmelanoma Skin Cancers

Abstract

Ingenol mebutate is a convenient, safe, and effective intervention for precancerous and cancerous skin conditions.

Reactivation of HIV latency by a newly modified Ingenol derivative via protein kinase Cδ–NF-κB signaling

“…Recently, an Ingenol ester compound, PICATO (ingenol mebutate), was approved by the US Food and Drug Administration (FDA) for treatment of skin precancer [68] (Fig. 5).…”

CH Oxidation of Ingenanes Enables Potent and Selective Protein Kinase C Isoform Activation

“…[5] This is reflected by comparing the biological activities of 12-Otetradecanoylphorbol-13-acetate (TPA), bryostatin 1, and ingenol mebutate (2): the first is as trong tumor promoter, the second shows antiproliferative properties,a nd latter has antitumoral properties and represents the active ingredient in Picato,amarketed product for the topical treatment of actinic keratosis (solar keratosis). [6] Thet wo-phase total synthesis of ingenol (1) [7] and the semisyntheses of ingenol mebutate (2) [8] and ingenol 3-amethylcyclohexanecarboxylate (3) [9] were reported previously ( Figure 1A). Tw o-phase terpene synthesis can both enable scalable access to the parent natural product and constitute atemplate for preparation of analogues with deepseated changes.…”

“…Finally,t ransformation of cyclase-phase endpoint 17 into ingenol analogue 14 led to another curious finding in oxidation chemistry (Path E): although 14 did not react under Pd(OH) 2 /TBHP conditions,it was successfully oxidized at C3 when using our recently developed Cr V -based allylic oxidation, [13] giving ingenane 26 with an inverted stereocenter at C3. This inversion of stereochemistry did not obstruct the synthetic plan, since it 26 was easily converted into analogues 11 and 9 in 1a nd 2 steps,respectively.Assuch, 10 new ingenol analogues (5)(6)(7)(8)(9)(10)(11)(12)(13)(14) were synthesized, with most of these products containing an a-methylcyclohexanecarboxylate ester for stability and potency. Thef eat of generating many derivatives with vastly different oxidation states was achieved by embracing the subtleties of CÀHoxidation in complex-molecule synthesis.…”

Synthesis of an Advanced Intermediate of the Jatrophane Diterpene Pl-4: A Dibromide Coupling Approach

“…6,7 Thus, it is not surprising that several Euphorbia species have been employed in traditional herbal folk medicines, mainly to treat cancerous conditions, swellings, and warts. 8 In particular, the MDR-reversing properties, more precisely, the selective inhibition of the ATP-dependent efflux pump p-glycoprotein, are of great interest to modern cancer research.…”