Tigilanol tiglate

Tigilanol tiglate (USAN;[1] previously known as EBC-46) is an experimental drug candidate being studied pre-clinically[2] by the Australian company Ecobiotics (specifically its drug discovery subsidiary Qbiotics). 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.[3]

Tigilanol tiglate

Clinical data
Trade names	Stelfonta
Other names	EBC-46
Routes of administration	Injection
ATCvet code	QL01XX91 (WHO)
Legal status
Legal status	In general: ℞ (Prescription only)
Identifiers
IUPAC name (1aR,1bR,1cS,2aR,3S,3aS,6aS,6bR,7R,8R,8aS)-3,3a,6b-Trihydroxy-2a-(hydroxymethyl)-1,1,5,7-tetramethyl-8a-{[(2S)-2-methylbutanoyl]oxy}-4-oxo-1a,1b,1c,2a,3,3a,4,6a,6b,7,8,8a-dodecahydro-1H-cyclopropa[5', 6']benzo[1',2':7,8]azuleno[5,6-b]oxiren-8-yl-(2E)-2-methyl-2-butenoate
CAS Number	943001-56-7^Y
PubChem CID	23627739
ChemSpider	32079087^N
UNII	R1ZJT87990
KEGG	D11191
Chemical and physical data
Formula	C30H42O10
Molar mass	562.656 g·mol^−1
3D model (JSmol)	Interactive image
SMILES CCC(C)C(=O)O[C@@]12[C@@H](C1(C)C)[C@@H]3[C@H]4[C@](O4)([C@H]([C@]5([C@H]([C@]3([C@@H]([C@H]2OC(=O)/C(=C/C)/C)C)O)C=C(C5=O)C)O)O)CO
InChI InChI=1S/C30H42O10/c1-9-13(3)23(33)38-21-16(6)28(36)17-11-15(5)20(32)29(17,37)25(35)27(12-31)22(39-27)18(28)19-26(7,8)30(19,21)40-24(34)14(4)10-2/h9,11,14,16-19,21-22,25,31,35-37H,10,12H2,1-8H3/b13-9+/t14?,16-,17+,18-,19-,21-,22+,25-,27+,28+,29-,30-/m1/s1^N Key:YLQZMOUMDYVSQR-YUKITULJSA-N^N
^NY (what is this?)  (verify)

The initial lead came from observation that marsupials found the seed of Fontainea picrosperma 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.[4]

Tigilanol tiglate is an extract from blushwood berries of Queensland, Australia.[2]

It is a tiglien-3-on derivative, with a tiglian backbone. Since the substance is obtained by extraction, impurities with other tiglian-3-one derivatives are possible.

The synthesis is currently only used to confirm the structure and is possible via the Wender synthesis.[5]

Tigilanol tiglate was approved for use in dogs in the European Union in January 2020.[6] It is indicated for the treatment of non-resectable, non-metastatic (WHO staging) subcutaneous mast cell tumours located at or distal to the elbow or the hock, and non-resectable, non metastatic cutaneous mast cell tumors in dogs.[6]

See also

• Ingenol mebutate
• Thapsigargin

References

1. "United States Adopted Name (USAN) Drug Finder" (PDF). United States Adopted Names. American Medical Association. Retrieved 20 February 2017.
2. Boyle GM, D'Souza MM, Pierce CJ, Adams RA, Cantor AS, Johns JP, et al. (2014). "Intra-lesional injection of the novel PKC activator EBC-46 rapidly ablates tumors in mouse models". PLOS ONE. 9 (10): e108887. Bibcode:2014PLoSO...9j8887B. doi:10.1371/journal.pone.0108887. PMC 4182759. PMID 25272271.
3. Aitken A (1987). "The activation of protein kinase G by daphnane, ingenane and tigliane diterpenoid esters". Botanical Journal of the Linnean Society. 94 (1–2): 247–263. doi:10.1111/j.1095-8339.1987.tb01049.x.
4. WO 2007070985, "Tiglian-3-one derivatives"
5. Wender PA, Kogen H, Lee HY, Munger JD, Wilhelm RS, Williams PD (1989). "Studies on tumor promoters. 8. The synthesis of phorbol". Journal of the American Chemical Society. 111 (24): 8957–8958. doi:10.1021/ja00206a050.
6. "Stelfonta EPAR". European Medicines Agency (EMA). 7 November 2019. Retrieved 13 May 2020. This article incorporates text from this source, which is in the public domain.

External links

• "Tigilanol tiglate". Drug Information Portal. U.S. National Library of Medicine.