Identification
- Generic Name
- Afimoxifene
- DrugBank Accession Number
- DB04468
- Background
Afimoxifene (4-Hydroxytamoxifen, trade name TamoGel) is a new estrogen inhibitor under investigation for a variety of estrogen-dependent conditions, including cyclic breast pain and gynecomastia. TamoGel is formulated using Enhanced Hydroalcoholic Gel (EHG) Technology. This technology enables percutaneous delivery of drugs that cannot be delivered orally. It is being developed by Ascent Therapeutics.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Afimoxifene (DB04468)
- Weight
- Average: 387.514
Monoisotopic: 387.219829177 - Chemical Formula
- C26H29NO2
- Synonyms
- 4-hydroxytamoxifen
- 4-monohydroxytamoxifen
- 4-OHT
- Afimoxifene
- External IDs
- 68047-06-3
- ICI-79280
Pharmacology
- Indication
For the potential treatment of menstrual-cycle related mastalgia, fibrocystic breast disease, breast disease, gynecomastia and Keloid scarring.
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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Not Available
- Mechanism of action
Afimoxifene binds to estrogen receptors (ER), inducing a conformational change in the receptor. This results in a blockage or change in the expression of estrogen dependent genes.
Target Actions Organism UTrefoil factor 1 Not Available Humans USteroid hormone receptor ERR1 inhibitorHumans UNuclear receptor subfamily 1 group I member 2 Not Available Humans USex hormone-binding globulin Not Available Humans UEstrogen receptor alpha Not Available Humans UEstrogen receptor beta Not Available Humans UEstrogen-related receptor gamma Not Available Humans - Absorption
Absorbed following topical application.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAmbroxol The risk or severity of methemoglobinemia can be increased when Afimoxifene is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Afimoxifene is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when Afimoxifene is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Afimoxifene is combined with Benzyl alcohol. Bupivacaine The risk or severity of methemoglobinemia can be increased when Afimoxifene is combined with Bupivacaine. - Food Interactions
- Not Available
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.- International/Other Brands
- Tamogel
Categories
- Drug Categories
- Androstanes
- Androstenes
- Androstenols
- Antineoplastic Agents
- Benzene Derivatives
- Benzylidene Compounds
- Estrogen Antagonists
- Estrogen Receptor Modulators
- Fused-Ring Compounds
- Hormone Antagonists
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Receptors, Estrogen, agonists
- Selective Estrogen Receptor Modulators
- Steroids
- Stilbenes
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
- Kingdom
- Organic compounds
- Super Class
- Phenylpropanoids and polyketides
- Class
- Stilbenes
- Sub Class
- Not Available
- Direct Parent
- Stilbenes
- Alternative Parents
- Diphenylmethanes / Phenylpropanes / Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / 1-hydroxy-2-unsubstituted benzenoids / Trialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- 1-hydroxy-2-unsubstituted benzenoid / Alkyl aryl ether / Amine / Aromatic homomonocyclic compound / Benzenoid / Diphenylmethane / Ether / Hydrocarbon derivative / Monocyclic benzene moiety / Organic nitrogen compound
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- tertiary amino compound, phenols (CHEBI:44616)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 95K54647BZ
- CAS number
- 68392-35-8
- InChI Key
- TXUZVZSFRXZGTL-QPLCGJKRSA-N
- InChI
- InChI=1S/C26H29NO2/c1-4-25(20-8-6-5-7-9-20)26(21-10-14-23(28)15-11-21)22-12-16-24(17-13-22)29-19-18-27(2)3/h5-17,28H,4,18-19H2,1-3H3/b26-25-
- IUPAC Name
- 4-[(1Z)-1-{4-[2-(dimethylamino)ethoxy]phenyl}-2-phenylbut-1-en-1-yl]phenol
- SMILES
- CC\C(=C(/C1=CC=C(O)C=C1)C1=CC=C(OCCN(C)C)C=C1)C1=CC=CC=C1
References
- General References
- Bollig A, Xu L, Thakur A, Wu J, Kuo TH, Liao JD: Regulation of intracellular calcium release and PP1alpha in a mechanism for 4-hydroxytamoxifen-induced cytotoxicity. Mol Cell Biochem. 2007 Nov;305(1-2):45-54. Epub 2007 Jul 24. [Article]
- Mansel R, Goyal A, Nestour EL, Masini-Eteve V, O'Connell K: A phase II trial of Afimoxifene (4-hydroxytamoxifen gel) for cyclical mastalgia in premenopausal women. Breast Cancer Res Treat. 2007 Dec;106(3):389-97. Epub 2007 Mar 10. [Article]
- Leblanc K, Sexton E, Parent S, Belanger G, Dery MC, Boucher V, Asselin E: Effects of 4-hydroxytamoxifen, raloxifene and ICI 182 780 on survival of uterine cancer cell lines in the presence and absence of exogenous estrogens. Int J Oncol. 2007 Feb;30(2):477-87. [Article]
- Cardoso CM, Almeida LM, Custodio JB: 4-Hydroxytamoxifen is a potent inhibitor of the mitochondrial permeability transition. Mitochondrion. 2002 Oct;1(6):485-95. [Article]
- External Links
- Human Metabolome Database
- HMDB0060530
- KEGG Drug
- D06551
- KEGG Compound
- C05011
- PubChem Compound
- 449459
- PubChem Substance
- 175426858
- ChemSpider
- 395987
- BindingDB
- 20608
- ChEBI
- 44616
- ChEMBL
- CHEMBL489
- ZINC
- ZINC000000902197
- PDBe Ligand
- OHT
- Wikipedia
- Afimoxifene
- PDB Entries
- 1s9q / 1vjb / 2bj4 / 2fsz / 2gpu / 2gpv / 2jf9 / 2p7z / 4q50 / 5w9c … show 4 more
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Terminated Treatment Mammographic Breast Density 1 2 Active Not Recruiting Prevention Mammographically Dense Breast 1 2 Completed Treatment Cyclic Breast Pain, Cyclic Mastalgia 1 2 Completed Treatment Ductal Breast Carcinoma In Situ / Estrogen Receptor Positive Breast Cancer 1 2 Recruiting Prevention Ductal Breast Carcinoma In Situ / Estrogen Receptor Positive 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00303 mg/mL ALOGPS logP 5.44 ALOGPS logP 5.48 Chemaxon logS -5.1 ALOGPS pKa (Strongest Acidic) 9.11 Chemaxon pKa (Strongest Basic) 8.5 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 32.7 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 130.41 m3·mol-1 Chemaxon Polarizability 45.22 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9936 Blood Brain Barrier - 0.6271 Caco-2 permeable + 0.8522 P-glycoprotein substrate Substrate 0.7715 P-glycoprotein inhibitor I Inhibitor 0.8359 P-glycoprotein inhibitor II Inhibitor 0.5471 Renal organic cation transporter Inhibitor 0.6067 CYP450 2C9 substrate Non-substrate 0.7876 CYP450 2D6 substrate Substrate 0.7641 CYP450 3A4 substrate Substrate 0.72 CYP450 1A2 substrate Inhibitor 0.7407 CYP450 2C9 inhibitor Non-inhibitor 0.8685 CYP450 2D6 inhibitor Inhibitor 0.7958 CYP450 2C19 inhibitor Non-inhibitor 0.8812 CYP450 3A4 inhibitor Non-inhibitor 0.831 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6389 Ames test Non AMES toxic 0.8955 Carcinogenicity Non-carcinogens 0.6202 Biodegradation Not ready biodegradable 0.83 Rat acute toxicity 1.9661 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.6942 hERG inhibition (predictor II) Inhibitor 0.6346
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 214.5857775 predictedDarkChem Lite v0.1.0 [M-H]- 196.4344 predictedDeepCCS 1.0 (2019) [M+H]+ 215.3934775 predictedDarkChem Lite v0.1.0 [M+H]+ 198.7924 predictedDeepCCS 1.0 (2019) [M+Na]+ 215.0396775 predictedDarkChem Lite v0.1.0 [M+Na]+ 205.02293 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Stabilizer of the mucous gel overlying the gastrointestinal mucosa that provides a physical barrier against various noxious agents. May inhibit the growth of calcium oxalate crystals in urine.
- Specific Function
- Growth factor activity
- Gene Name
- TFF1
- Uniprot ID
- P04155
- Uniprot Name
- Trefoil factor 1
- Molecular Weight
- 9149.435 Da
References
- Krieg AJ, Krieg SA, Ahn BS, Shapiro DJ: Interplay between estrogen response element sequence and ligands controls in vivo binding of estrogen receptor to regulated genes. J Biol Chem. 2004 Feb 6;279(6):5025-34. Epub 2003 Nov 14. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and...
- Gene Name
- ESRRA
- Uniprot ID
- P11474
- Uniprot Name
- Steroid hormone receptor ERR1
- Molecular Weight
- 45509.11 Da
References
- Huppunen J, Aarnisalo P: Dimerization modulates the activity of the orphan nuclear receptor ERRgamma. Biochem Biophys Res Commun. 2004 Feb 20;314(4):964-70. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Zinc ion binding
- Specific Function
- Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
- Gene Name
- NR1I2
- Uniprot ID
- O75469
- Uniprot Name
- Nuclear receptor subfamily 1 group I member 2
- Molecular Weight
- 49761.245 Da
References
- Kretschmer XC, Baldwin WS: CAR and PXR: xenosensors of endocrine disrupters? Chem Biol Interact. 2005 Aug 15;155(3):111-28. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Androgen binding
- Specific Function
- Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone...
- Gene Name
- SHBG
- Uniprot ID
- P04278
- Uniprot Name
- Sex hormone-binding globulin
- Molecular Weight
- 43778.755 Da
References
- Hong H, Branham WS, Ng HW, Moland CL, Dial SL, Fang H, Perkins R, Sheehan D, Tong W: Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and alpha-fetoprotein. Toxicol Sci. 2015 Feb;143(2):333-48. doi: 10.1093/toxsci/kfu231. Epub 2014 Oct 27. [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
- Reed CA, Berndtson AK, Nephew KP: Dose-dependent effects of 4-hydroxytamoxifen, the active metabolite of tamoxifen, on estrogen receptor-alpha expression in the rat uterus. Anticancer Drugs. 2005 Jun;16(5):559-67. [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
- Reed CA, Berndtson AK, Nephew KP: Dose-dependent effects of 4-hydroxytamoxifen, the active metabolite of tamoxifen, on estrogen receptor-alpha expression in the rat uterus. Anticancer Drugs. 2005 Jun;16(5):559-67. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Zinc ion binding
- Specific Function
- Orphan receptor that acts as transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response ...
- Gene Name
- ESRRG
- Uniprot ID
- P62508
- Uniprot Name
- Estrogen-related receptor gamma
- Molecular Weight
- 51305.485 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
Drug created at June 13, 2005 13:24 / Updated at June 12, 2020 16:52