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Trade names | Stelfonta |
Other names | EBC-46 |
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Routes of administration | Injection |
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Formula | C30H42O10 |
Molar mass | 562.656 g·mol−1 |
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Tigilanol tiglate (USAN; [1] ), sold under the brand name Stelfonta is a medication used to treat dogs with non-metastatic, skin-based (cutaneous) mast cell tumors (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. [2] Stelfonta is injected directly into the MCT (intratumoral injection). Stelfonta works by activating a protein that spreads throughout the treated tumor, 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.[ citation needed ]
Initially, the synthesis was only used to confirm the structure and is possible via the Wender synthesis. [3] In 2022, the Wender group reported an efficient semi-synthesis of tigilanol tiglate from phorbol (12% overall yield over 12 steps). [4]
Tigilanol tiglate was approved for use in dogs in the European Union in January 2020. [5] 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. [5]
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. [6] It was discovered through an automated screening process of natural products 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 ester which, along with other related compounds, acts as a protein kinase C regulator. [7]
The initial lead came from observation that marsupials found the seed of Fontainea picrosperma (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. [8]
Tigilanol tiglate is an extract from blushwood berries of Queensland, Australia. [9]
Gefitinib, sold under the brand name Iressa, is a medication used for certain breast, lung and other cancers. Gefitinib is an EGFR inhibitor, like erlotinib, which interrupts signaling through the epidermal growth factor receptor (EGFR) in target cells. Therefore, it is only effective in cancers with mutated and overactive EGFR, but resistances to gefitinib can arise through other mutations. It is marketed by AstraZeneca and Teva.
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.
Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology (immuno-oncology) and a growing subspecialty of oncology.
Quinazoline is an organic compound with the formula C8H6N2. It is an aromatic heterocycle with a bicyclic structure consisting of two fused six-membered aromatic rings, a benzene ring and a pyrimidine ring. It is a light yellow crystalline solid that is soluble in water. Also known as 1,3-diazanaphthalene, quinazoline received its name from being an aza derivative of quinoline. Though the parent quinazoline molecule is rarely mentioned by itself in technical literature, substituted derivatives have been synthesized for medicinal purposes such as antimalarial and anticancer agents. Quinazoline is a planar molecule. It is isomeric with the other diazanaphthalenes of the benzodiazine subgroup: cinnoline, quinoxaline, and phthalazine. Over 200 biologically active quinazoline and quinoline alkaloids are identified.
Melphalan, sold under the brand name Alkeran among others, is a chemotherapy medication used to treat multiple myeloma; malignant lymphoma; lymphoblastic and myeloblastic leukemia; childhood neuroblastoma; ovarian cancer; mammary adenocarcinoma; and uveal melanoma. It is taken by mouth or by injection into a vein.
Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells. Because most agents for targeted therapy are biopharmaceuticals, the term biologic therapy is sometimes synonymous with targeted therapy when used in the context of cancer therapy. However, the modalities can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy.
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, Croton tiglium. The structure of phorbol was determined in 1967. Various esters of phorbol have important biological properties, the most notable of which is the capacity to act as tumor promoters through activation of protein kinase C. They mimic diacylglycerols, glycerol derivatives in which two hydroxyl groups have reacted with fatty acids to form esters. The most common and potent phorbol ester is 12-O-tetradecanoylphorbol-13-acetate (TPA), also called phorbol-12-myristate-13-acetate (PMA), which is used as a biomedical research tool in contexts such as models of carcinogenesis.
Lapatinib (INN), used in the form of lapatinib ditosylate (USAN) is an orally active drug for breast cancer and other solid tumours. It is a dual tyrosine kinase inhibitor which interrupts the HER2/neu and epidermal growth factor receptor (EGFR) pathways. It is used in combination therapy for HER2-positive breast cancer. It is used for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 (ErbB2).
PAC-1 is a synthesized chemical compound that selectively induces apoptosis, in cancerous cells. It was granted orphan drug status by the FDA in 2016.
KRAS is a gene that provides instructions for making a protein called K-Ras, a part of the RAS/MAPK pathway. The protein relays signals from outside the cell to the cell's nucleus. These signals instruct the cell to grow and divide (proliferate) or to mature and take on specialized functions (differentiate). It is called KRAS because it was first identified as a viral oncogene in the KirstenRAt Sarcoma virus. The oncogene identified was derived from a cellular genome, so KRAS, when found in a cellular genome, is called a proto-oncogene.
Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.
Temsirolimus, sold under the brand name Torisel, is an intravenous drug for the treatment of renal cell carcinoma (RCC), developed by Wyeth Pharmaceuticals and approved by the U.S. Food and Drug Administration (FDA) in May 2007, and was also approved by the European Medicines Agency (EMA) in November 2007. It is a derivative and prodrug of sirolimus.
Eribulin, sold under the brand name Halaven among others, is an anti-cancer medication used to treat breast cancer and liposarcoma.
Interferon alfa (INN) or HuIFN-alpha-Le, trade name Multiferon, is a pharmaceutical drug composed of natural interferon alpha (IFN-α), obtained from the leukocyte fraction of human blood following induction with Sendai virus. Interferon alfa contains several naturally occurring IFN-α subtypes and is purified by affinity chromatography. Although the pharmaceutical product is often simply called "interferon alpha" or "IFN-α" like its endogenous counterpart, the product's International nonproprietary name (INN) is interferon alfa.
Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast cancer. It is administered by slow intravenous injection.
Binimetinib, sold under the brand name Mektovi, is an anti-cancer medication used to treat various cancers. Binimetinib is a selective inhibitor of MEK, a central kinase in the tumor-promoting MAPK pathway. Inappropriate activation of the pathway has been shown to occur in many cancers. In June 2018 it was approved by the FDA in combination with encorafenib for the treatment of patients with unresectable or metastatic BRAF V600E or V600K mutation-positive melanoma. In October 2023, it was approved by the FDA for treatment of NSCLC with a BRAF V600E mutation in combination with encorafenib. It was developed by Array Biopharma.
Atezolizumab, sold under the brand name Tecentriq among others, is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma and alveolar soft part sarcoma, but discontinued for use in triple-negative breast cancer (TNBC). It is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1 (PD-L1).
Osimertinib, sold under the brand name Tagrisso, is a medication used to treat non-small-cell lung carcinomas with specific mutations. It is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor.
Abemaciclib, sold under the brand name Verzenio among others, is a medication for the treatment of advanced or metastatic breast cancers. It was developed by Eli Lilly and it acts as a CDK inhibitor selective for CDK4 and CDK6.
A mastocytoma in dogs is a neoplasm (neoplasia) originating from mast cells in the domestic dog, which occurs mainly in the skin and subcutis. Mastocytoma are not only extremely common in dogs, but also tend to be much more malignant in them than in other animal species. The average survival time for malignant tumors is only four months, whereas for benign tumors it is over two years.