Ingenol Mebutate

Ingenol mebutate, also known as ingenol-3-angelate, is a substance found in the sap of the plant Euphorbia peplus and an inducer of cell death. Ingenol Mebutate was approved for the topical treatment of actinic keratosis. Ingenol mebutate has also been found to be useful for reactivating latent HIV virus in cells taken from individuals who have tested negative for signs of the disease following extended courses of anti-retroviral drugs, raising the possibility that this drug may be used to expose the last traces of virus, and thus potentially provide a permanent cure for HIV infection.

Product information

CAS Number: 75567-37-2

Molecular Weight: 416.55

Formula: C25H36O5

Synonym:

PEP-005

ingenol-3-angelate

Picato

Chemical Name: (Z)-(1aS,5R,5aS,6S,9R)-5,5a-dihydroxy-4-(hydroxymethyl)-1,1,7,9-tetramethyl-1a,2,5,5a,6,9,10,10a-octahydro-1H-2,8a-methanocyclopenta[a]cyclopropa[e][10]annulen-6-yl 2-methylbut-2-enoate

Smiles: CC1(C)[C@@H]2C1C[C@@H](C)C13CC2C=C(CO)[C@@H](O)[C@]1(O)[C@@H](OC(=O)C(C)=CC)C(C)=C3

InChiKey: KIBVFXDTJVSNKX-IFOWAPEYSA-N

InChi: InChI=1S/C25H36O5/c1-7-13(2)22(28)30-21-14(3)10-24-11-16(9-17(12-26)20(27)25(21,24)29)19-18(8-15(24)4)23(19,5)6/h7,9-10,15-16,18-21,26-27,29H,8,11-12H2,1-6H3/b13-7+/t15-,16?,18?,19+,20-,21+,24?,25+/m1/s1

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: soluble in DMSO, not soluble in water.

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Ingenol Mebutate (Ingenol 3-angelate) is an active ingredient in Euphorbia peplus, acting as a potent PKC activator, with Kis of 0.3, 0.105, 0.162, 0.376, and 0.171 nM for PKC-α, PKC-β, PKC-γ, PKC-δ, and PKC-ε, respectively. Ingenol Mebutate also EC50s of 13 ± 2.4 nM (PKC-α), 4.37 ± 0.4 nM (PKC-βI), 10.5 ± 2.2 nM (PKC-βII), 38.6 ± 2.9 nM (PKC-δ), 1.08 ± 0.01 nM (PKC-ε), 0.9 ± 0.13 nM (PKC-μ) in WEHI-231 cells, 198 ± 12.5 nM (PKC-α), 69.1 ± 8.2 nM (PKC-βI), 4.6 ± 0.4 nM (PKC-ε) and 1 nM (PKC-μ) in HOP-92 cells, 635 ± 245 nM (PKC-α), 146 ± 35 nM (PKC-βI), 4.7 ± 0.7 nM (PKC-δ), 1.1 ± 0.5 nM (PKC-ε), and 30 nM (PKC-μ) in Colo-205 cells. Ingenol Mebutate sensitizes WEHI-231 cells, HOP-92 and Colo-205 cells, with IC50s of 1.41 ± 0.255 nM, 3.24 ± 2.01 nM, and 11.9 ± 1.307 nM, respectively. Ingenol Mebutate (PEP005; 20 nM) actions are PKC-δ dependent, induces apoptosis in primary AML marrow blasts but not in normal myeloblasts. Ingenol Mebutate (PEP005) activates PKCδ and inhibits PKCα. Colo205-R cells (IC50: >10 μM) are >300-fold more resistant to Ingenol Mebutate than parental Colo205-S cells.

References:

1. Bobyr I, Campanati A, Consales V, Giangiacomi M, Diotallevi F, Offidani A. Granuloma faciale successfully treated with ingenol mebutate. Dermatol Ther. 2016 Jun 30. doi: 10.1111/dth.12368. [Epub ahead of print] PubMed PMID: 27364361.
2. Bettencourt MS. Tolerability of Ingenol Mebutate Gel, 0.05%, for Treating Patients with Actinic Keratosis on the Scalp in a Community Dermatology Practice. J Clin Aesthet Dermatol. 2016 Mar;9(3):20-4. Epub 2016 Mar 1. PubMed PMID: 27354884; PubMed Central PMCID: PMC4896817.
3. Flórez Á, Batalla A, de la Torre C. Management of actinic cheilitis using ingenol mebutate gel: A report of seven cases. J Dermatolog Treat. 2016 May 31:1-3. [Epub ahead of print] PubMed PMID: 27241280.

Products are for research use only. Not for human use.