Identification
- Summary
Enzacamene is an ingredient used in sunscreen to block UVB radiation.
- Generic Name
- Enzacamene
- DrugBank Accession Number
- DB11219
- Background
Commonly known as 4-methylbenzylidene-camphor (4-MBC), enzacamene is a camphor derivative and an organic chemical UV-B filter. It is used in cosmetic products such as sunscreen to provide skin protection against UV rays. While its effects on the human reproductive system as an endocrine disruptor are being investigated, its use in over-the-counter and cosmetic products is approved by Health Canada. Its tradenames include Eusolex 6300 (Merck) and Parsol 5000 (DSM).
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Enzacamene (DB11219)
- Weight
- Average: 254.373
Monoisotopic: 254.167065328 - Chemical Formula
- C18H22O
- Synonyms
- (+/-)-3-(p-methylbenzylidene)camphor
- 3-(4-methylbenzylidene)camphor
- 3-(p-Methylbenzylidene)-DL-camphor
- 4-MBC
- 4-methylbenzylidene camphor
- enzacamène
- Enzacamene
- Enzacamene D-L form
- enzacameno
- enzacamenum
- Methyl benzylidene camphor
Pharmacology
- Indication
Indicated for use as an active sunscreen agent.
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Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Several studies suggest that enzacamene elicit estrogen-like effects. In prepubertal male rats exposed to enzacamene during embryonic and fetal development, decrease in testicular weight with decreased levels of LH, GnRH, and glutamate were observed; in comparison, there was an increase in LH, GnRH, and aspartate levels in peripubertal rats 2. These findings suggest that high concentrations of enzacamene during embryonic and fetal stage inhibits the testicular axis in male rats during the prepubertal stage and stimulates it during peripubertad stage 2. In a study of zebrafish (Danio rerio) embryo, exposure to enzacamene during early vertebrate development was associated with muscular and neuronal defects that may result in developmental defects, including a reduction in AChE activity, disorganized pattern of slow muscle fibers, and axon pathfinding errors during motor neuron innervation 5. Enzacamene displays a weak binding activity in receptors binding assays using the mammalian estrogen receptor (ER) 4.
- Mechanism of action
Enzacamene absorbs UV-B rays. It is proposed that enzacamene exerts estrogen-like activities in the same direction as endogenous estrogens via nonclassical estrogen signaling mechanisms that do not involve gene regulation by the nuclear ER 4. It binds to cytosolic estradiol binding sites of estrogen receptors with low to moderate affinity compared to that of the endogenous agonist. Based on the findings of a study with Xenopus hepatocytes in culture, enzacamene has a potential to induce the ER gene only at higher concentrations (10–100 μmol/L). While enzacamene was not shown to activate estrogen-dependent gene transcription when tested in an ER reporter gene assay in yeast cells, it was demonstrated in Xenopus hepatocytes cultures that activate ER-dependent signaling mechanisms leading to altered gene expression 4. In micromolar concentrations, enzacamene accelerates cell proliferation rate in MCF-7 human breast cancer cells 4.
Target Actions Organism UProgesterone receptor antagonistHumans UAndrogen receptor antagonistHumans UEstrogen receptor beta Not Available Humans UEstrogen receptor alpha Not Available Humans - Absorption
The maximum plasma concentration of enzacamene was 16ng/mL in healthy female volunteers following daily whole-body topical application of 2mg/cm^2 of sunscreen formulation at 10% (weight/weight) for four days 1. Blood concentration of enzacamene (4-MBC) and its main metabolite, 3-(4-carboxybenzylidene)camphor, peaked within 10 h after oral administration of enzacamene 6.
- Volume of distribution
No pharmacokinetic data available.
- Protein binding
No pharmacokinetic data available.
- Metabolism
Based on the findings of a rat pharmacokinetic study, it is proposed that absorbed enzacamene following oral administration undergo extensive first-pass hepatic metabolism 6. Following oral administration of enzacamene (4-MBC) in rats, detected metabolites in the plasma and urine were 3-(4-carboxybenzylidene)camphor and as four isomers of 3-(4-carboxybenzylidene)hydroxycamphor containing the hydroxyl group located in the camphor ring system with 3-(4-carboxybenzylidene)-6-hydroxycamphor as the major metabolite. However the blood concentrations of 3-(4-carboxybenzylidene)-6-hydroxycamphor were below the limit of detection following peak concentration 6.
Via hydroxylation mediated by cytochrome P450 system, 3-(4-hydroxymethylbenzylidene)camphor is formed. This metabolite is further oxidized to 3-(4-carboxybenzylidene)camphor via oxidation of alcohol dehydrogenase and aldehyde dehydrogenase, and may be further hydroxylated to form 3-(4-carboxybenzylidene)-6-hydroxycamphor mediated by CYP450 system 6.
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- Route of elimination
The urine concentration of 4 ng/mL and 4 ng/mL of enzacamene were observed in female and male volunteers, respectively 3. In a rat pharmacokinetic study, most of orally administered enzacamene was recovered in in feces as 3-(4-carboxybenzylidene)camphor and, to a smaller extent, as 3-(4-carboxybenzylidene)-6-hydroxycamphor 6. Glucuronides of both metabolites were also detectable in faces 6. In urine, one isomer of 3-(4-carboxybenzylidene)hydroxycamphor was the predominant metabolite [3-(4-carboxybenzylidene)-6-hydroxycamphor], the other isomers and 3-(4-carboxybenzylidene)camphor were only minor metabolites excreted with urine 6. Enterohepatic circulation of glucuronides derived from the two major 4-MBC metabolites may explain the slow excretion of 4-MBC metabolites with urine and the small percentage of the administered doses recovered in urine 6.
- Half-life
The half life of enzacamene (4-MBC) and its main metabolite, 3-(4-carboxybenzylidene)camphor, displayed half-lives of approximately 15 h after reaching peak plasma concentrations after oral administration in rats 6.
- Clearance
No pharmacokinetic data available.
- Adverse Effects
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Oral LD50 and dermal LD50 in rat are reported to be 10,000 mg/kg 7. Oral TDLO in rat is 7 mg/kg MSDS. Oral and subcutaneous TDLO following continuous administration in rat are 476 mg/kg/4D and 4 mg/kg/2D, respectively MSDS. Cases of overdose have not been reported for enzacamene. Enzacamene is reported to be an endocrine disruptor that alters the reproductive axis.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Over the Counter Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Snik Crm 6% Cream 6 % Topical Austria Import West Ltd. 1997-09-10 2003-07-29 Canada 
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Anthelios L - Ecran Intolerances Solaires SPF 60 Enzacamene (5 %) + Avobenzone (3.5 %) + Ecamsule (3.3 %) + Titanium dioxide (4 %) Cream Topical Laboratoires La Roche Posay Canada 1999-03-01 2009-06-05 Canada Anthelios L-lait Ecran Intol.solaire SPF 60 Enzacamene (5 %) + Avobenzone (3.5 %) + Ecamsule (3.3 %) + Titanium dioxide (4 %) Lotion Topical Cosmair Canada Inc. 1996-12-31 2001-07-27 Canada Anthelios S - Ecran Solaire SPF 30 Enzacamene (5 %) + Avobenzone (2 %) + Ecamsule (2 %) + Titanium dioxide (4 %) Cream Topical Laboratoires La Roche Posay Canada 1997-05-29 2010-06-08 Canada Anthelios-creme Solaire SPF 10 Enzacamene (3 %) + Avobenzone (3 %) + Ecamsule (2 %) + Titanium dioxide (1.7 %) Cream Topical Cosmair Canada Inc. 1996-12-31 1998-08-12 Canada Anthelios-ecran Invisible SPF 20 Enzacamene (5 %) + Avobenzone (2 %) + Ecamsule (2 %) + Titanium dioxide (2.5 %) Cream Topical Cosmair Canada Inc. 1996-12-31 1998-08-12 Canada Anthelios-lait Ecran Invisible SPF 20 Enzacamene (5 %) + Avobenzone (2 %) + Ecamsule (2 %) + Titanium dioxide (2.5 %) Lotion Topical Cosmair Canada Inc. 1996-12-31 1998-08-12 Canada Anthelios-stick Ecran SPF 30 Enzacamene (6 %) + Avobenzone (3 %) Stick Topical Cosmair Canada Inc. 1996-06-27 1999-03-16 Canada Antherpos-ceralip Solaire SPF 50 Enzacamene (6 %) + Avobenzone (2 %) + Ecamsule (1 %) + Titanium dioxide (4 %) Cream Topical Laboratoires La Roche Posay Canada 1996-12-31 2008-07-23 Canada Autobronzant Creme Fps 15 Enzacamene (4 %) + Avobenzone (2 %) + Ecamsule (1 %) + Octocrylene (10 %) Cream Topical Ombrelle Canada 2001-03-31 2005-07-22 Canada Autobronzant SPF 7 Enzacamene (4 %) + Avobenzone (2 %) + Ecamsule (0.7 %) Gel Topical Vichy Canada 1999-04-20 2002-08-01 Canada - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Conju Princess UV Sun Block Enzacamene (0.05 mL/1mL) + Avobenzone (0.03 mL/1mL) + Octinoxate (0.075 mL/1mL) + Titanium dioxide (0.0249 mL/1mL) + Zinc oxide (0.01 mL/1mL) Cream Topical Conju Inc 2010-12-18 Not applicable US 
Conju Princess UV Sun Block Enzacamene (0.05 mL/1mL) + Avobenzone (0.03 mL/1mL) + Octinoxate (0.075 mL/1mL) + Titanium dioxide (0.0249 mL/1mL) + Zinc oxide (0.01 mL/1mL) Cream Topical Conju Inc 2010-12-18 Not applicable US Laser Block 100 sunblock Enzacamene (0.03 mL/1mL) + Amiloxate (0.02 mL/1mL) + Avobenzone (0.005 mL/1mL) + Octinoxate (0.07 mL/1mL) + Titanium dioxide (0.02 mL/1mL) + Zinc oxide (0.05 mL/1mL) Cream Topical Universal Cosmetic Co., Ltd 2010-08-04 Not applicable US MediSpa Sunblock sunblock Enzacamene (0.03 mL/1mL) + Avobenzone (0.005 mL/1mL) + Octinoxate (0.07 mL/1mL) + Zinc oxide (0.05 mL/1mL) Cream Topical Universal Cosmetic Co., Ltd 2010-08-04 Not applicable US MediSpa SunSpray sunblock Enzacamene (0.05 mL/1mL) + Octinoxate (0.075 mL/1mL) + Octocrylene (0.01 mL/1mL) Spray Topical Universal Cosmetic Co., Ltd 2010-08-06 Not applicable US Outback 2-in-1 Insect Repellent and Protective Sunscreen Enzacamene (13 mg/1mL) + Octinoxate (90 mg/1mL) + Zinc oxide (80 mg/1mL) Cream Topical Elmore Oil Company Pty Ltd 2012-07-01 Not applicable US Secret Key Natural Cc Cushion Spf50 Pa / 02 Natural Cc Enzacamene (3 g/100g) + Octinoxate (7 g/100g) + Octisalate (3 g/100g) + Titanium dioxide (12 g/100g) Liquid Topical Zenpia 2015-07-05 2016-08-01 US Secret Key Natural Cc Cushion Spf50 Plus / 01 Light Cc Enzacamene (3 g/100g) + Octinoxate (7 g/100g) + Octisalate (3 g/100g) + Titanium dioxide (12 g/100g) Liquid Topical Zenpia 2015-07-05 2018-12-19 US Secret Key Natural Cc Cushion Spf50 Plus / 02 Natural Cc Enzacamene (3 g/100g) + Octinoxate (7 g/100g) + Octisalate (3 g/100g) + Titanium dioxide (12 g/100g) Liquid Topical Zenpia 2015-07-05 2018-12-19 US
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 8I3XWY40L9
- CAS number
- 36861-47-9
- InChI Key
- HEOCBCNFKCOKBX-SDNWHVSQSA-N
- InChI
- InChI=1S/C18H22O/c1-12-5-7-13(8-6-12)11-14-15-9-10-18(4,16(14)19)17(15,2)3/h5-8,11,15H,9-10H2,1-4H3/b14-11+
- IUPAC Name
- (3E)-1,7,7-trimethyl-3-[(4-methylphenyl)methylidene]bicyclo[2.2.1]heptan-2-one
- SMILES
- CC1=CC=C(\C=C2/C3CCC(C)(C2=O)C3(C)C)C=C1
References
- General References
- Latha MS, Martis J, Shobha V, Sham Shinde R, Bangera S, Krishnankutty B, Bellary S, Varughese S, Rao P, Naveen Kumar BR: Sunscreening agents: a review. J Clin Aesthet Dermatol. 2013 Jan;6(1):16-26. [Article]
- Carou ME, Szwarcfarb B, Deguiz ML, Reynoso R, Carbone S, Moguilevsky JA, Scacchi P, Ponzo OJ: Impact of 4-methylbenzylidene-camphor (4-MBC) during embryonic and fetal development in the neuroendocrine regulation of testicular axis in prepubertal and peripubertal male rats. Exp Clin Endocrinol Diabetes. 2009 Oct;117(9):449-54. [Article]
- Janjua NR, Kongshoj B, Andersson AM, Wulf HC: Sunscreens in human plasma and urine after repeated whole-body topical application. J Eur Acad Dermatol Venereol. 2008 Apr;22(4):456-61. doi: 10.1111/j.1468-3083.2007.02492.x. Epub 2008 Jan 23. [Article]
- Klann A, Levy G, Lutz I, Muller C, Kloas W, Hildebrandt JP: Estrogen-like effects of ultraviolet screen 3-(4-methylbenzylidene)-camphor (Eusolex 6300) on cell proliferation and gene induction in mammalian and amphibian cells. Environ Res. 2005 Mar;97(3):274-81. doi: 10.1016/j.envres.2004.07.004. [Article]
- Li VW, Tsui MP, Chen X, Hui MN, Jin L, Lam RH, Yu RM, Murphy MB, Cheng J, Lam PK, Cheng SH: Effects of 4-methylbenzylidene camphor (4-MBC) on neuronal and muscular development in zebrafish (Danio rerio) embryos. Environ Sci Pollut Res Int. 2016 May;23(9):8275-85. doi: 10.1007/s11356-016-6180-9. Epub 2016 Feb 18. [Article]
- Volkel W, Colnot T, Schauer UM, Broschard TH, Dekant W: Toxicokinetics and biotransformation of 3-(4-methylbenzylidene)camphor in rats after oral administration. Toxicol Appl Pharmacol. 2006 Oct 15;216(2):331-8. doi: 10.1016/j.taap.2006.05.012. Epub 2006 May 23. [Article]
- OPINION ON 4-Methylbenzylidene camphor (4-MBC) - European Union [File]
- External Links
- PubChem Compound
- 7019255
- PubChem Substance
- 347827944
- ChemSpider
- 4939160
- BindingDB
- 50103609
- 1311507
- ChEBI
- 135937
- ChEMBL
- CHEMBL2104261
- Wikipedia
- Enzacamene
- MSDS
- Download (26.4 KB)
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Stick Topical Emulsion Topical Gel Topical Spray Topical Lotion Topical Cream Topical Liquid Topical Cream Topical 6 % - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 66-69 European Commission SCCP: Opinion on 4-methylbenzylidene camphor (4-MBC) water solubility Poorly soluble European Commission SCCP: Opinion on 4-methylbenzylidene camphor (4-MBC) logP 5.14 European Commission SCCP: Opinion on 4-methylbenzylidene camphor (4-MBC) - Predicted Properties
Property Value Source Water Solubility 0.0051 mg/mL ALOGPS logP 5.09 ALOGPS logP 5.12 Chemaxon logS -4.7 ALOGPS pKa (Strongest Basic) -5.2 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 1 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 17.07 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 79.68 m3·mol-1 Chemaxon Polarizability 30.58 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Zinc ion binding
- Specific Function
- The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor ...
- Gene Name
- PGR
- Uniprot ID
- P06401
- Uniprot Name
- Progesterone receptor
- Molecular Weight
- 98979.96 Da
References
- Schreurs RH, Sonneveld E, Jansen JH, Seinen W, van der Burg B: Interaction of polycyclic musks and UV filters with the estrogen receptor (ER), androgen receptor (AR), and progesterone receptor (PR) in reporter gene bioassays. Toxicol Sci. 2005 Feb;83(2):264-72. Epub 2004 Nov 10. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Zinc ion binding
- Specific Function
- Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription ...
- Gene Name
- AR
- Uniprot ID
- P10275
- Uniprot Name
- Androgen receptor
- Molecular Weight
- 98987.9 Da
References
- Schreurs RH, Sonneveld E, Jansen JH, Seinen W, van der Burg B: Interaction of polycyclic musks and UV filters with the estrogen receptor (ER), androgen receptor (AR), and progesterone receptor (PR) in reporter gene bioassays. Toxicol Sci. 2005 Feb;83(2):264-72. Epub 2004 Nov 10. [Article]
- Jimenez-Diaz I, Molina-Molina JM, Zafra-Gomez A, Ballesteros O, Navalon A, Real M, Saenz JM, Fernandez MF, Olea N: Simultaneous determination of the UV-filters benzyl salicylate, phenyl salicylate, octyl salicylate, homosalate, 3-(4-methylbenzylidene) camphor and 3-benzylidene camphor in human placental tissue by LC-MS/MS. Assessment of their in vitro endocrine activity. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Oct 1;936:80-7. doi: 10.1016/j.jchromb.2013.08.006. Epub 2013 Aug 8. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Zinc ion binding
- Specific Function
- Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent m...
- Gene Name
- ESR2
- Uniprot ID
- Q92731
- Uniprot Name
- Estrogen receptor beta
- Molecular Weight
- 59215.765 Da
References
- Matsumoto H, Adachi S, Suzuki Y: [Estrogenic activity of ultraviolet absorbers and the related compounds]. Yakugaku Zasshi. 2005 Aug;125(8):643-52. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Zinc ion binding
- Specific Function
- Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissu...
- Gene Name
- ESR1
- Uniprot ID
- P03372
- Uniprot Name
- Estrogen receptor
- Molecular Weight
- 66215.45 Da
References
- Matsumoto H, Adachi S, Suzuki Y: [Estrogenic activity of ultraviolet absorbers and the related compounds]. Yakugaku Zasshi. 2005 Aug;125(8):643-52. [Article]
- Jimenez-Diaz I, Molina-Molina JM, Zafra-Gomez A, Ballesteros O, Navalon A, Real M, Saenz JM, Fernandez MF, Olea N: Simultaneous determination of the UV-filters benzyl salicylate, phenyl salicylate, octyl salicylate, homosalate, 3-(4-methylbenzylidene) camphor and 3-benzylidene camphor in human placental tissue by LC-MS/MS. Assessment of their in vitro endocrine activity. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Oct 1;936:80-7. doi: 10.1016/j.jchromb.2013.08.006. Epub 2013 Aug 8. [Article]
Drug created at December 03, 2015 16:51 / Updated at March 21, 2023 17:58