Tigilanol tiglate (

USAN 280px, "Samguk Sagi" Book 04. Silla's Records. In 512, Usan-guk（于山國）was Ulleungdo（鬱陵島） Usan-guk, or the State of Usan, occupied Ulleung-do and the adjacent islands during the Korean Three Kingdoms period. According to th ...

; ), sold under the brand name Stelfonta is a

medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...

used to treat

dog The dog (''Canis familiaris'' or ''Canis lupus familiaris'') is a domesticated descendant of the wolf. Also called the domestic dog, it is derived from the extinct Pleistocene wolf, and the modern wolf is the dog's nearest living relative. Do ...

s with non-

metastatic Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

, skin-based (

cutaneous Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different de ...

)

mast cell tumor A mastocytoma or mast cell tumor is a type of round-cell tumor consisting of mast cells. It is found in humans and many animal species; it also can refer to an accumulation or nodule of mast cells that resembles a tumor. Mast cells originate f ...

s (MCTs). The FDA is also approving Stelfonta to treat non-metastatic MCTs located under the dog's skin ( subcutaneous), in particular areas of a dog's leg. Stelfonta is injected directly into the MCT (intratumoral injection). Stelfonta works by activating a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that spreads throughout the treated

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

, which disintegrates tumor cells. It is a tiglien-3-on derivative, with a tigliane backbone. Since the substance is obtained by extraction, impurities with other tiglian-3-one derivatives are possible. Initially, the synthesis was only used to confirm the structure and is possible via the Wender synthesis. In 2022, the Wender group reported an efficient semi-synthesis of tigilanol tiglate from phorbol (12% overall yield over 12 steps). Tigilanol tiglate was approved for use in dogs in the European Union in January 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. It is indicated for the treatment of non-resectable, non-metastatic (WHO staging) subcutaneous mast cell tumors located at or distal to the elbow or the hock, and non-resectable, non metastatic cutaneous mast cell tumors in dogs.

Research

Tigilanol tiglate is an experimental drug candidate being studied in phase I and II human trials by the Australian company Ecobiotics (specifically its drug discovery subsidiary Qbiotics) in partnership with MSD. It was discovered through an automated screening process of

natural product A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical syn ...

s by selecting increasingly purified fractions of plant extracts, based on their ability to produce the desired activity profile. This is then followed by artificial synthesis of the isolated compound to confirm its chemical structure. Tigilanol tiglate is a

phorbol Phorbol is a natural, plant-derived organic compound. It is a member of the tigliane family of diterpenes. Phorbol was first isolated in 1934 as the hydrolysis product of croton oil, which is derived from the seeds of the purging croton, '' Croto ...

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...

which, along with other related compounds, acts as a

protein kinase C In cell biology, Protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and t ...

regulator. The initial lead came from observation that

marsupial Marsupials are any members of the mammalian infraclass Marsupialia. All extant marsupials are endemic to Australasia, Wallacea and the Americas. A distinctive characteristic common to most of these species is that the young are carried in a po ...

s found the seed of ''

Fontainea picrosperma ''Fontainea picrosperma'', commonly known as the blushwood tree, is a rainforest tree in the family Euphorbiaceae endemic to Queensland in Australia, where it grows on the Atherton Tablelands. Uses An anti-cancer drug known as EBC-46 has been ...

'' (blushwood) unpalatable due to an inflammatory chemical present in reasonably high concentrations. This was identified as 12-tigloyl-13-(2-methylbutanoyl)-6,7-epoxy-4,5,9,12,13,20-hexahydroxy-1-tiglian-3-one. Tigilanol tiglate is an extract from blushwood berries of Queensland, Australia.

References

External links

* Antineoplastic drugs Experimental cancer drugs Diterpenes Cyclopropanes Alcohols Alkene derivatives Ketones Carboxylate esters Epoxides Veterinary drugs {{pharma-stub