Ingenol Mebutate | PEP005 | CAS#75567-37-2 | inducer of cell death

MedKoo Cat#: 201545 | Name: Ingenol Mebutate

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

Ingenol Mebutate

CAS#75567-37-2

Theoretical Analysis

MedKoo Cat#: 201545

Name: Ingenol Mebutate

CAS#: 75567-37-2

Chemical Formula: C25H34O6

Exact Mass: 430.2355

Molecular Weight: 430.53

Elemental Analysis: C, 69.74; H, 7.96; O, 22.30

Price and Availability

Size	Price	Availability
1mg	USD 90.00	Ready to ship
5mg	USD 250.00	Ready to ship
10mg	USD 450.00	Ready to ship
25mg	USD 950.00	Ready to ship
50mg	USD 1,650.00	Ready to ship
100mg	USD 2,950.00	Ready to ship
200mg	USD 4,850.00	Ready to ship

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Related CAS #

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Synonym

PEP005; PEP-005; PEP 005; ingenol-3-angelate, Ingenol mebutate; trade name Picato

IUPAC/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

InChi Key

VDJHFHXMUKFKET-RGSPJFHZSA-N

InChi Code

InChI=1S/C25H34O6/c1-7-12(2)22(29)31-21-13(3)10-24-14(4)8-17-18(23(17,5)6)16(20(24)28)9-15(11-26)19(27)25(21,24)30/h7,9-10,14,16-19,21,26-27,30H,8,11H2,1-6H3/b12-7-/t14-,16?,17?,18-,19-,21+,24?,25+/m1/s1

SMILES Code

C/C=C(C)\C(O[C@H]1C(C)=CC23[C@]1(O)[C@H](O)C(CO)=CC(C3=O)[C@]4([H])C(C4(C)C)C[C@H]2C)=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

soluble in DMSO, not soluble in water.

Shelf Life

>5 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#TZC60711

QC Data

View QC data: current batch, Lot#TZC60711

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Ingenol Mebutate acts as a PKC modulator 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.

In vitro activity:

Ingenol mebutat (IM) significantly and dose-dependently induced the expression of proinflammatory chemokines (CXCL8, CCL2) and AMP (RNase7, HBD3) in human epithelial keratinocytes (HEK) and epithelial cancer cell lines. A significantly stronger induction of CXCL8 and CCL2 was observed in tested tumor cells as compared to HEK. No significant effect was observed of IM on HEK migration, respectively wound healing responses in vitro for any tested concentration (10-9, 10-8, 10-6 M) except 10-7 M, which induced a significant inhibition. Reference: Eur J Med Res. 2018 Sep 28;23(1):45. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161468/

In vivo activity:

In two in vivo murine studies, ingenol mebutate's effect on photodamage and squamous cell carcinoma formation was investigated. Mice were irradiated with solar simulated ultraviolet radiation. During the first 20 weeks, 5 single applications with ingenol mebutate were given at four-week intervals. Prophylactic treatments with ingenol mebutate prevented progression of histological photodamage of all investigated characteristics, including keratosis grade, epidermal hypertrophy, dysplasia, and dermal actinic damage. In addition, tumor formation was postponed by 3 weeks. Reference: Dan Med J. 2017 Nov;64(11):B5368. https://ugeskriftet.dk/dmj/exploring-use-ingenol-mebutate-prevent

	Solvent	mg/mL	mM
Solubility
	DMSO	100.0	232.27

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 430.53 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Braun SA, Baran J, Schrumpf H, Buhren BA, Bölke E, Homey B, Gerber PA. Ingenol mebutate induces a tumor cell-directed inflammatory response and antimicrobial peptides thereby promoting rapid tumor destruction and wound healing. Eur J Med Res. 2018 Sep 28;23(1):45. doi: 10.1186/s40001-018-0343-8. PMID: 30266096; PMCID: PMC6161468. 2. Erlendsson AM. Exploring the use of ingenol mebutate to prevent non-melanoma skin cancer. Dan Med J. 2017 Nov;64(11):B5368. PMID: 29115209.

In vitro protocol:

In vivo protocol:

1. Erlendsson AM. Exploring the use of ingenol mebutate to prevent non-melanoma skin cancer. Dan Med J. 2017 Nov;64(11):B5368. PMID: 29115209.

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: Bobyr I, Campanati A, Consales V, Giuliodori K, Scalise A, Offidani A. Efficacy, safety and tolerability of field treatment of actinic keratosis with ingenol mebutate 0.015 % gel: a single center case series. Springerplus. 2016 May 14;5:627. doi: 10.1186/s40064-016-2290-6. eCollection 2016. PubMed PMID: 27330893; PubMed Central PMCID: PMC4870479. 4: Monfrecola G, Scalvenzi M, Costa C, Cantelli M, Fabbrocini G. Ingenol mebutate for pigmented superficial basal cell carcinomas: evaluation by confocal microscopy. G Ital Dermatol Venereol. 2016 Jun 10. [Epub ahead of print] PubMed PMID: 27284778. 5: 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. 6: Braun SA, Gerber PA. Successful treatment of perianal condylomata acuminata with ingenol mebutate gel. J Dtsch Dermatol Ges. 2016 Jun;14(6):616-7. doi: 10.1111/ddg.12879. Epub 2016 May 17. PubMed PMID: 27187666. 7: Berman B, Stockfleth E. Field Treatment of Actinic Keratosis With Ingenol Mebutate. J Drugs Dermatol. 2016 May 1;15(5):535-42. PubMed PMID: 27168262. 8: Emilio J, Schwartz M, Feldman E, Bieber AK, Bienenfeld A, Jung MK, Siegel DM, Markowitz O. Improved patient satisfaction using ingenol mebutate gel 0.015% for the treatment of facial actinic keratoses: a prospective pilot study. Clin Cosmet Investig Dermatol. 2016 Apr 20;9:89-93. doi: 10.2147/CCID.S100999. eCollection 2016. PubMed PMID: 27143946; PubMed Central PMCID: PMC4845892. 9: Elías I, Ortega-Joaquín N, de la Cueva P, Del Pozo LJ, Moreno-Ramírez D, Boada A, Aguilar M, Mirada A, Mosquera E, Gibbons C, Oyagüez I. Cost-Effectiveness and Cost-Utility Analysis of Ingenol Mebutate Versus Diclofenac 3% and Imiquimod 5% in the Treatment of Actinic Keratosis in Spain. Actas Dermosifiliogr. 2016 Jul-Aug;107(6):498-508. doi: 10.1016/j.ad.2016.03.004. Epub 2016 Apr 26. English, Spanish. PubMed PMID: 27130804. 10: Le TT, Skak K, Schroder K, Schroder WA, Boyle GM, Pierce CJ, Suhrbier A. IL-1 Contributes to the Anti-Cancer Efficacy of Ingenol Mebutate. PLoS One. 2016 Apr 21;11(4):e0153975. doi: 10.1371/journal.pone.0153975. eCollection 2016. PubMed PMID: 27100888; PubMed Central PMCID: PMC4839727. 11: Grandi V, Delfino C, Pimpinelli N. Ingenol mebutate in the treatment of 'Hydroxyurea-induced Squamous Dysplasia': a single centre experience. J Eur Acad Dermatol Venereol. 2016 Jul;30(7):1129-32. doi: 10.1111/jdv.13616. Epub 2016 Apr 13. PubMed PMID: 27072602. 12: Hanke WC, Norlin JM, Mark Knudsen K, Larsson T, Stone S. Quality of life in treatment of AK: Treatment burden of ingenol mebutate gel is small and short lasting. J Dermatolog Treat. 2016 Apr 7:1-6. [Epub ahead of print] PubMed PMID: 27052110. 13: Mohanna M, Hofbauer G. Pronounced local skin reaction to ingenol mebutate against actinic keratosis in kidney transplant recipient without systemic adverse events. JAAD Case Rep. 2015 Nov 24;1(6):S19-22. doi: 10.1016/j.jdcr.2015.09.011. eCollection 2015 Nov. PubMed PMID: 27051801; PubMed Central PMCID: PMC4809621. 14: Ricci F, Tambone S, Neri L, Fania L, Piccioni A, Guerriero C, Fargnoli MC, Peris K. Real-life efficacy and safety of ingenol mebutate for the treatment of actinic keratosis of the face and scalp: A single arm retrospective study. J Dermatolog Treat. 2016 Apr 4:1-6. [Epub ahead of print] PubMed PMID: 27043050. 15: Garmyn M. Ingenol mebutate for actinic keratosis: a field-directed therapy with short duration. Br J Dermatol. 2016 Mar;174(3):481-2. doi: 10.1111/bjd.14429. PubMed PMID: 27002568. 16: Salleras Redonnet M, Quintana Codina M. Ingenol mebutate gel for the treatment of Bowen's disease: a case report of three patients. Dermatol Ther. 2016 Mar 11. doi: 10.1111/dth.12344. [Epub ahead of print] PubMed PMID: 26969886. 17: Kim C, Hashemi P, Caglia M, Shulman K. Treatment of Imiquimod Resistant Epidermodysplasia Verruciformis With Ingenol Mebutate. J Drugs Dermatol. 2016 Mar 1;15(3):350-2. PubMed PMID: 26954321. 18: Bhandari PR, Pai VV. Could ingenol mebutate be useful in managing nonmelanoma skin cancers? Indian J Cancer. 2015 Apr-Jun;52(2):249-50. doi: 10.4103/0019-509X.175820. PubMed PMID: 26853424. 19: Longo C, Borsari S, Benati E, Moscarella E, Alfano R, Argenziano G. Dermoscopy and Reflectance Confocal Microscopy for Monitoring the Treatment of Actinic Keratosis with Ingenol Mebutate Gel: Report of Two Cases. Dermatol Ther (Heidelb). 2016 Mar;6(1):81-7. doi: 10.1007/s13555-016-0094-9. Epub 2016 Feb 4. PubMed PMID: 26847171; PubMed Central PMCID: PMC4799035. 20: Erlendsson AM, Karmisholt KE, Haak CS, Stender IM, Haedersdal M. Topical corticosteroid has no influence on inflammation or efficacy after ingenol mebutate treatment of grade I to III actinic keratoses (AK): A randomized clinical trial. J Am Acad Dermatol. 2016 Apr;74(4):709-15. doi: 10.1016/j.jaad.2015.11.034. Epub 2016 Jan 22. PubMed PMID: 26810403.