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Identification
NameImiquimod
Accession NumberDB00724  (APRD01030)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Imiquimod is an immune response modifier that acts as a toll-like receptor 7 agonist. Imiquimod is commonly used topically to treat warts on the skin of the genital and anal areas. Imiquimod does not cure warts, and new warts may appear during treatment. Imiquimod does not fight the viruses that cause warts directly, however, it does help to relieve and control wart production. Miquimod is also used to treat a skin condition of the face and scalp called actinic keratoses and certain types of skin cancer called superficial basal cell carcinoma.

Structure
Thumb
Synonyms
1-Isobutyl-1H-imidazo[4,5-c]quinolin-4-amine
4-Amino-1-isobutyl-1H-imidazo(4,5-c)quinoline
Imiquimod
Imiquimodum
R 837
Zartra
External Identifiers
  • R-837
  • S 26308
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Aldaracream50 mg/gtopicalMedicis Pharmaceutical Corp2011-11-28Not applicableUs
Aldara Pcream5 %topicalValeant Canada Lp Valeant Canada S.E.C.1999-07-05Not applicableCanada
Imiquimodcream50 mg/1000mgtopicalPerrigo New York Inc.2010-04-20Not applicableUs
Imiquimod 5%cream50 mgtopicalValeant Canada Lp Valeant Canada S.E.C.Not applicableNot applicableCanada
Vylomacream3.75 %topicalValeant Canada Lp Valeant Canada S.E.C.2011-04-19Not applicableCanada
Zyclaracream3.75 %topicalValeant Canada Lp Valeant Canada S.E.C.2010-01-27Not applicableCanada
Zyclaracream2.5 mg/gtopicalMedicis Pharmaceutical Corp2012-02-29Not applicableUs
Zyclaracream37.5 mg/gtopicalMedicis Pharmaceutical Corp2012-01-01Not applicableUs
Zyclaracream37.5 mg/gtopicalMedicis Pharmaceutical Corp2011-11-28Not applicableUs
Zyclaracream2.5 %topicalValeant Canada Lp Valeant Canada S.E.C.Not applicableNot applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-imiquimodcream5 %topicalApotex Inc2013-12-31Not applicableCanada
Imiquimodcream50 mg/gtopicalE. Fougera & Co. a division of Fougera Pharmaceuticals Inc.2010-02-25Not applicableUs
Imiquimodcream50 mg/gtopicalStrides Arcolab Limited2014-07-07Not applicableUs
Imiquimodcream50 mg/1000mgtopicalApotex Corp.2012-09-14Not applicableUs
Imiquimodcream50 mg/gtopicalPhysicians Total Care, Inc.2010-09-22Not applicableUs
Imiquimodcream50 mg/gtopicalTaro Pharmaceutical Industries Ltd.2011-04-15Not applicableUs
Imiquimodcream50 mg/gtopicalImpax Generics2011-02-28Not applicableUs
Imiquimodcream50 mg/gtopicalTaro Pharmaceuticals U.S.A., Inc.2011-04-15Not applicableUs
Imiquimodcream12.5 mg/.25gtopicalPerrigo New York Inc2010-11-09Not applicableUs
Imiquimodcream50 mg/gtopicalGlenmark Pharmaceuticals Inc., Usa2012-03-06Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
BeselnaMochida
ImimorePanalab
ImiquadGlenmark
LabimiqITF - Labomed
Li DiMingxin Pharmaceutical
MiquimodLazar
Nan BoTopfond Pharmaceutical
NilwartDr. Reddy's
OmiquidarDarier
Tian RuiYangtze River Pharma
VetlandLandsteiner
You CareNang Kuang
YoubiqingThe United Laboratories Ltd
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Imiquimod acetate
ThumbNot applicableDBSALT000970
Categories
UNIIP1QW714R7M
CAS number99011-02-6
WeightAverage: 240.3036
Monoisotopic: 240.137496532
Chemical FormulaC14H16N4
InChI KeyInChIKey=DOUYETYNHWVLEO-UHFFFAOYSA-N
InChI
InChI=1S/C14H16N4/c1-9(2)7-18-8-16-12-13(18)10-5-3-4-6-11(10)17-14(12)15/h3-6,8-9H,7H2,1-2H3,(H2,15,17)
IUPAC Name
1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine
SMILES
CC(C)CN1C=NC2=C1C1=CC=CC=C1N=C2N
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as aminoquinolines and derivatives. These are organic compounds containing an amino group attached to a quinoline ring system.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassQuinolines and derivatives
Sub ClassAminoquinolines and derivatives
Direct ParentAminoquinolines and derivatives
Alternative Parents
Substituents
  • Aminoquinoline
  • Imidazopyridine
  • Aminopyridine
  • Imidolactam
  • Benzenoid
  • Pyridine
  • Primary aromatic amine
  • N-substituted imidazole
  • Heteroaromatic compound
  • Imidazole
  • Azole
  • Azacycle
  • Hydrocarbon derivative
  • Primary amine
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the topical treatment of clinically typical, nonhyperkeratotic, nonhypertrophic actinic keratoses on the face or scalp in immunocompetent adults. Also indicated for the treatment of external genital and perianal warts/condyloma acuminata in individuals 12 years old and above.
PharmacodynamicsImiquimod is an immune response modifier that acts as a toll-like receptor 7 agonist. Imiquimod is commonly used topically to treat warts on the skin of the genital and anal areas. Imiquimod does not cure warts, and new warts may appear during treatment. Imiquimod does not fight the viruses that cause warts directly, however, it does help to relieve and control wart production. It is not used on warts inside the vagina, penis, or rectum. Imiquimod is also used to treat a skin condition of the face and scalp called actinic keratoses. Imiquimod can also be used to treat certain types of skin cancer called superficial basal cell carcinoma. Imiquimod is particularly useful on areas where surgery or other treatments may be difficult, complicated or otherwise undesirable, especially the face and lower legs.
Mechanism of actionImiquimod's mechanism of action is via stimulation of innate and acquired immune responses, which ultimately leads to inflammatory cell infiltration within the field of drug application followed by apoptosis of diseased tissue. Imiquimod does not have direct antiviral activity. Studies of mice show that imiquimod may induce cytokines, including interferon-alpha (IFNA) as well as several IFNA genes (IFNA1, IFNA2, IFNA5, IFNA6, and IFNA8) as well as the IFNB gene. Imiquimod also induced the expression of interleukin (IL)-6, IL-8, and tumor necrosis factor alpha genes. In the treatment of basal cell carcinoma, Imiquimod appears to act as a toll-like receptor-7 agonist, and is thought to exert its anti-tumor effect via modification of the immune response and stimulation of apoptosis in BCC cells. In treating basal cell carcinoma it may increase the infiltration of lymphocytes, dendritic cells, and macrophages into the tumor lesion.
Related Articles
AbsorptionWell absorbed through skin (as a cream)
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half life20 hours (topical dose), 2 hours (subcutaneous dose)
ClearanceNot Available
ToxicitySymptoms of overdose include flu-like symptoms, such as fever, fatigue, headache, nausea, diarrhoea and muscle pain.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9967
Blood Brain Barrier+0.955
Caco-2 permeable+0.5995
P-glycoprotein substrateNon-substrate0.5137
P-glycoprotein inhibitor INon-inhibitor0.8797
P-glycoprotein inhibitor IIInhibitor0.6949
Renal organic cation transporterNon-inhibitor0.5928
CYP450 2C9 substrateNon-substrate0.8625
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.51
CYP450 1A2 substrateInhibitor0.8751
CYP450 2C9 inhibitorNon-inhibitor0.8182
CYP450 2D6 inhibitorInhibitor0.7628
CYP450 2C19 inhibitorNon-inhibitor0.634
CYP450 3A4 inhibitorNon-inhibitor0.5131
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6829
Ames testAMES toxic0.8884
CarcinogenicityNon-carcinogens0.8917
BiodegradationNot ready biodegradable0.9916
Rat acute toxicity2.5683 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9546
hERG inhibition (predictor II)Inhibitor0.5422
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Graceway pharmaceuticals llc
  • Nycomed us inc
  • Graceway Pharmaceuticals, LLC
Packagers
Dosage forms
FormRouteStrength
Creamtopical5 %
Creamtopical12.5 mg/.25g
Creamtopical50 mg/g
Creamtopical50 mg/1000mg
Creamtopical50 mg
Creamtopical2.5 %
Creamtopical2.5 mg/g
Creamtopical3.75 %
Creamtopical37.5 mg/g
Prices
Unit descriptionCostUnit
Aldara 5% Cream Pack46.99USD pack
Imiquimod 5% Cream Packet42.89USD packet
Imiquimod 5% cream33.17USD each
Aldara 5% cream26.04USD each
Zyclara 3.75% cream24.43USD each
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US4689338 No1992-08-252009-08-25Us
US7696159 Yes2004-10-012024-10-01Us
US8222270 No2009-12-112029-12-11Us
US8236816 No2009-12-112029-12-11Us
US8299109 No2009-12-112029-12-11Us
US8598196 No2009-08-182029-08-18Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point292-294 °CNot Available
water solubilityPoorly solubleNot Available
logP2.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.247 mg/mLALOGPS
logP2.83ALOGPS
logP2.65ChemAxon
logS-3ALOGPS
pKa (Strongest Basic)5.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area56.73 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity72.54 m3·mol-1ChemAxon
Polarizability26.67 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US4689338
General References
  1. van Egmond S, Hoedemaker C, Sinclair R: Successful treatment of perianal Bowen's disease with imiquimod. Int J Dermatol. 2007 Mar;46(3):318-9. [PubMed:17343595 ]
  2. Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, Horiuchi T, Tomizawa H, Takeda K, Akira S: Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol. 2002 Feb;3(2):196-200. Epub 2002 Jan 22. [PubMed:11812998 ]
  3. Bilu D, Sauder DN: Imiquimod: modes of action. Br J Dermatol. 2003 Nov;149 Suppl 66:5-8. [PubMed:14616337 ]
  4. Miller RL, Gerster JF, Owens ML, Slade HB, Tomai MA: Imiquimod applied topically: a novel immune response modifier and new class of drug. Int J Immunopharmacol. 1999 Jan;21(1):1-14. [PubMed:10411278 ]
External Links
ATC CodesD06BB10
AHFS Codes
  • 84:92.00
PDB EntriesNot Available
FDA labelDownload (144 KB)
MSDSDownload (36.3 KB)
Interactions
Drug Interactions
Drug
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Imiquimod.
LeflunomideThe risk or severity of adverse effects can be increased when Imiquimod is combined with Leflunomide.
NatalizumabThe risk or severity of adverse effects can be increased when Imiquimod is combined with Natalizumab.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Imiquimod.
RoflumilastRoflumilast may increase the immunosuppressive activities of Imiquimod.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Imiquimod.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Imiquimod.
TofacitinibImiquimod may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Imiquimod.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Transmembrane signaling receptor activity
Specific Function:
Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR7 is a nucleotide-sensing TLR which is activated by single-stranded RNA. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (By similarity).
Gene Name:
TLR7
Uniprot ID:
Q9NYK1
Molecular Weight:
120920.8 Da
References
  1. Gibson SJ, Lindh JM, Riter TR, Gleason RM, Rogers LM, Fuller AE, Oesterich JL, Gorden KB, Qiu X, McKane SW, Noelle RJ, Miller RL, Kedl RM, Fitzgerald-Bocarsly P, Tomai MA, Vasilakos JP: Plasmacytoid dendritic cells produce cytokines and mature in response to the TLR7 agonists, imiquimod and resiquimod. Cell Immunol. 2002 Jul-Aug;218(1-2):74-86. [PubMed:12470615 ]
  2. Akira S, Hemmi H: Recognition of pathogen-associated molecular patterns by TLR family. Immunol Lett. 2003 Jan 22;85(2):85-95. [PubMed:12527213 ]
  3. Dummer R, Urosevic M, Kempf W, Hoek K, Hafner J, Burg G: Imiquimod in basal cell carcinoma: how does it work? Br J Dermatol. 2003 Nov;149 Suppl 66:57-8. [PubMed:14616353 ]
  4. Otero M, Calarota SA, Felber B, Laddy D, Pavlakis G, Boyer JD, Weiner DB: Resiquimod is a modest adjuvant for HIV-1 gag-based genetic immunization in a mouse model. Vaccine. 2004 Apr 16;22(13-14):1782-90. [PubMed:15068862 ]
  5. Ambach A, Bonnekoh B, Nguyen M, Schon MP, Gollnick H: Imiquimod, a Toll-like receptor-7 agonist, induces perforin in cytotoxic T lymphocytes in vitro. Mol Immunol. 2004 Apr;40(18):1307-14. [PubMed:15072849 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
General Function:
Single-stranded rna binding
Specific Function:
Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.
Gene Name:
TLR8
Uniprot ID:
Q9NR97
Molecular Weight:
119826.82 Da
References
  1. Dummer R, Urosevic M, Kempf W, Hoek K, Hafner J, Burg G: Imiquimod in basal cell carcinoma: how does it work? Br J Dermatol. 2003 Nov;149 Suppl 66:57-8. [PubMed:14616353 ]
  2. Zhu J, Lai K, Brownile R, Babiuk LA, Mutwiri GK: Porcine TLR8 and TLR7 are both activated by a selective TLR7 ligand, imiquimod. Mol Immunol. 2008 Jun;45(11):3238-43. doi: 10.1016/j.molimm.2008.02.028. Epub 2008 Apr 24. [PubMed:18439678 ]
  3. Gorden KB, Gorski KS, Gibson SJ, Kedl RM, Kieper WC, Qiu X, Tomai MA, Alkan SS, Vasilakos JP: Synthetic TLR agonists reveal functional differences between human TLR7 and TLR8. J Immunol. 2005 Feb 1;174(3):1259-68. [PubMed:15661881 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on July 23, 2016 03:08