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Identification
NameAzelaic Acid
Accession NumberDB00548  (APRD00812, EXPT00598)
TypeSmall Molecule
GroupsApproved
Description

Azelaic acid is a saturated dicarboxylic acid found naturally in wheat, rye, and barley. It is a natural substance that is produced by Malassezia furfur (also known as Pityrosporum ovale), a yeast that lives on normal skin. It is effective against a number of skin conditions, such as mild to moderate acne, when applied topically in a cream formulation of 20%. It works in part by stopping the growth of skin bacteria that cause acne, and by keeping skin pores clear. Azelaic acid’s antimicrobial action may be attributable to inhibition of microbial cellular protein synthesis.

Structure
Thumb
Synonyms
1,7-Dicarboxyheptane
1,7-Heptanedicarboxylic acid
1,9-Nonanedioic acid
Acide azélaïque
Ácido azelaico
Acidum acelaicum
Acidum azelaicum
Anchoic acid
Azelaic acid
Azelainsaeure
Azelainsäure
Azelex
Finacea
Lepargylic acid
N-Nonanedioic acid
Nonandisaeure
Nonandisäure
Nonanedioic acid
Skinoren
External Identifiers
  • UNII-F2VW3D43YT
  • ZK 62498
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Azelaic Acidgel.15 g/gtopicalAlvogen, Inc.2015-07-08Not applicableUs
Azelexcream.2 g/gcutaneousAllergan, Inc.1996-03-21Not applicableUs
Azelexcream.2 g/gcutaneousPhysicians Total Care, Inc.2007-05-31Not applicableUs
Finaceagel.15 g/gtopicalBayer Health Care Pharmaceuticals Inc.2002-12-24Not applicableUs
FinaceakitIntendis Inc.2011-04-12Not applicableUs
Finaceagel15 %topicalBayer Inc2010-06-15Not applicableCanada
Finaceagel.15 g/gtopicalIntendis Inc.2004-12-24Not applicableUs
Finaceagel.15 g/gtopicalPhysicians Total Care, Inc.2005-03-03Not applicableUs
Finacea Foamaerosol, foam.15 g/gtopicalBayer Health Care Pharmaceuticals Inc.2015-08-03Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Elcure Ac-lex Serumliquid2.5 mL/50mLtopicalElcure Co., Ltd.2011-11-24Not applicableUs
International Brands
NameCompany
Acne-DermUnia
AcneanNewai Chem
AcnedermEgo
AcnesafeZ-Jans Pharma
AknorenHerbacos Recordati
AmiEverest
ArbonidIntermed
FinevinBerlex
SkinorenBayer
ZumilinFarmedia
Brand mixtures
NameLabellerIngredients
Vp-zelVirtus Pharmaceuticals
SaltsNot Available
Categories
UNIIF2VW3D43YT
CAS number123-99-9
WeightAverage: 188.2209
Monoisotopic: 188.104859
Chemical FormulaC9H16O4
InChI KeyInChIKey=BDJRBEYXGGNYIS-UHFFFAOYSA-N
InChI
InChI=1S/C9H16O4/c10-8(11)6-4-2-1-3-5-7-9(12)13/h1-7H2,(H,10,11)(H,12,13)
IUPAC Name
nonanedioic acid
SMILES
OC(=O)CCCCCCCC(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as medium-chain fatty acids. These are fatty acids with an aliphatic tail that contains between 4 and 12 carbon atoms.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassFatty acids and conjugates
Direct ParentMedium-chain fatty acids
Alternative Parents
Substituents
  • Medium-chain fatty acid
  • Dicarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Pharmacology
IndicationFor the topical treatment of mild-to-moderate inflammatory acne vulgaris.
PharmacodynamicsAzelaic acid is a saturated dicarboxylic acid found naturally in wheat, rye, and barley. It is a natural substance that is produced by Malassezia furfur (also known as Pityrosporum ovale), a yeast that lives on normal skin. It is effective against a number of skin conditions, such as mild to moderate acne, when applied topically in a cream formulation of 20%. It works in part by stopping the growth of skin bacteria that cause acne, and by keeping skin pores clear. Azelaic acid's antimicrobial action may be attributable to inhibition of microbial cellular protein synthesis.
Mechanism of actionThe exact mechanism of action of azelaic acid is not known. It is thought that azelaic acid manifests its antibacterial effects by inhibiting the synthesis of cellular protein in anaerobic and aerobic bacteria, especially Staphylococcus epidermidis and Propionibacterium acnes. In aerobic bacteria, azelaic acid reversibly inhibits several oxidoreductive enzymes including tyrosinase, mitochondrial enzymes of the respiratory chain, thioredoxin reductase, 5-alpha-reductase, and DNA polymerases. In anaerobic bacteria, azelaic acid impedes glycolysis. Along with these actions, azelaic acid also improves acne vulgaris by normalizing the keratin process and decreasing microcomedo formation. Azelaic acid may be effective against both inflamed and noninflamed lesions. Specifically, azelaic acid reduces the thickness of the stratum corneum, shrinks keratohyalin granules by reducing the amount and distribution of filaggrin (a component of keratohyalin) in epidermal layers, and lowers the number of keratohyalin granules.
Related Articles
AbsorptionApproximately 4% of the topically applied azelaic acid is systemically absorbed.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Mainly excreted unchanged in the urine but undergoes some b-oxidation to shorter chain dicarboxylic acids.

Route of eliminationAzelaic acid is mainly excreted unchanged in the urine, but undergoes some ß-oxidation to shorter chain dicarboxylic acids.
Half lifeThe observed half-lives in healthy subjects are approximately 45 minutes after oral dosing and 12 hours after topical dosing, indicating percutaneous absorption rate-limited kinetics.
ClearanceNot Available
ToxicityOral LD50 in rat: >5 g/kg
Affected organisms
  • Various aerobic and anaerobic microorganisms
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.5731
Blood Brain Barrier+0.7397
Caco-2 permeable-0.6412
P-glycoprotein substrateNon-substrate0.6969
P-glycoprotein inhibitor INon-inhibitor0.9845
P-glycoprotein inhibitor IINon-inhibitor0.9229
Renal organic cation transporterNon-inhibitor0.9359
CYP450 2C9 substrateNon-substrate0.8447
CYP450 2D6 substrateNon-substrate0.905
CYP450 3A4 substrateNon-substrate0.7534
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.939
CYP450 2D6 inhibitorNon-inhibitor0.9729
CYP450 2C19 inhibitorNon-inhibitor0.9762
CYP450 3A4 inhibitorNon-inhibitor0.96
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9927
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.8382
BiodegradationReady biodegradable0.8506
Rat acute toxicity1.3577 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9348
hERG inhibition (predictor II)Non-inhibitor0.9602
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Allergan inc
  • Intendis inc
Packagers
Dosage forms
FormRouteStrength
Creamcutaneous.2 g/g
Liquidtopical2.5 mL/50mL
Geltopical.15 g/g
Geltopical15 %
Kit
Aerosol, foamtopical.15 g/g
Tablet, coatedoral
Prices
Unit descriptionCostUnit
Azelex 20% Cream 50 gm Tube262.74USD tube
Azelex 20% Cream 30 gm Tube181.32USD tube
Finacea 15% Gel 50 gm Tube162.28USD tube
Finacea plus kit143.15USD kit
Azelex 20% cream5.21USD g
Finacea 15% gel2.86USD g
Azelaic acid flakes1.05USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2311128 No2008-01-292018-11-18Canada
US6534070 No1998-11-182018-11-18Us
US6730288 No1999-09-082019-09-08Us
US7700076 No2007-09-182027-09-18Us
US8435498 No2004-03-012024-03-01Us
US8722021 No2003-10-242023-10-24Us
US8900554 No2003-10-242023-10-24Us
US9211259 No2009-01-262029-01-26Us
US9265725 No2007-12-082027-12-08Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point106.5 °CPhysProp
boiling point286.5 °C at 1.00E+02 mm HgPhysProp
water solubility2400 mg/L (at 20 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP1.57HANSCH,C ET AL. (1995)
logS-1.89ADME Research, USCD
pKa4.55 (at 25 °C)KORTUM,G ET AL (1961)
Predicted Properties
PropertyValueSource
Water Solubility2.28 mg/mLALOGPS
logP1.37ALOGPS
logP1.82ChemAxon
logS-1.9ALOGPS
pKa (Strongest Acidic)4.15ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area74.6 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity46.54 m3·mol-1ChemAxon
Polarizability20.5 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (10.6 KB)
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-0v0r-4920000000-5a3ed693b1c4083f1f15View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Negative (Annotated)splash10-000i-0900000000-a118e433f0bd27a95b89View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Negative (Annotated)splash10-006t-9600000000-93b3a375b722791cb5c9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Negative (Annotated)splash10-052k-9500000000-6b069f2fed947651b284View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-000i-0900000000-7980b5eadcca6ee1eaddView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-004i-0900000000-462585874f7661d40d5bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-004j-4900000000-0f65eeeed8c8a6ff3cc9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-0002-9300000000-d654ca3c764066f98358View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negativesplash10-0002-9000000000-60a08bb384f2b4cbfca8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00dr-0900000000-b1b7c1ab57d58a2405a8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00g3-2900000000-d0ba7fbbe987efa4c818View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-05qd-9100000000-8d65a19b998d18ad08acView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0900000000-a7edc3ac66d27685b9d1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00kr-1900000000-c56b9d972f88c58dc65bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4l-9300000000-47cbefe19a788d7f36b9View in MoNA
MSMass Spectrum (Electron Ionization)splash10-06rx-9100000000-6db2acb47ad4c6163063View in MoNA
1D NMR1H NMR SpectrumNot Available
1D NMR1H NMR SpectrumNot Available
1D NMR13C NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
References
Synthesis Reference

Abdul Malek, Clevys J. Monasterios, G. Ronald Brown, Ved P. Gupta, “Two step oxidation process for the production of carboxylic acids such as azelaic acid from unsaturated substrates.” U.S. Patent US5380928, issued October, 1981.

US5380928
General ReferencesNot Available
External Links
ATC CodesD10AX03
AHFS CodesNot Available
PDB Entries
FDA labelDownload (389 KB)
MSDSDownload (72.9 KB)
Interactions
Drug InteractionsNo interactions found.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Staphylococcus aureus (strain Mu50 / ATCC 700699)
Pharmacological action
yes
Actions
inhibitor
General Function:
Thioredoxin-disulfide reductase activity
Specific Function:
Not Available
Gene Name:
trxB
Uniprot ID:
P66010
Molecular Weight:
33615.84 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Schallreuter KU, Wood JM: Azelaic acid as a competitive inhibitor of thioredoxin reductase in human melanoma cells. Cancer Lett. 1987 Sep;36(3):297-305. [PubMed:3652030 ]
  4. Hojo Y, Saito Y, Tanimoto T, Hoefen RJ, Baines CP, Yamamoto K, Haendeler J, Asmis R, Berk BC: Fluid shear stress attenuates hydrogen peroxide-induced c-Jun NH2-terminal kinase activation via a glutathione reductase-mediated mechanism. Circ Res. 2002 Oct 18;91(8):712-8. [PubMed:12386148 ]
  5. Schallreuter KU, Wood JW: A possible mechanism of action for azelaic acid in the human epidermis. Arch Dermatol Res. 1990;282(3):168-71. [PubMed:2114832 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Steroid binding
Specific Function:
Efficiently catalyzes the reduction of progesterone, androstenedione, 17-alpha-hydroxyprogesterone and testosterone to 5-beta-reduced metabolites. The bile acid intermediates 7-alpha,12-alpha-dihydroxy-4-cholesten-3-one and 7-alpha-hydroxy-4-cholesten-3-one can also act as substrates.
Gene Name:
AKR1D1
Uniprot ID:
P51857
Molecular Weight:
37376.615 Da
References
  1. Stamatiadis D, Bulteau-Portois MC, Mowszowicz I: Inhibition of 5 alpha-reductase activity in human skin by zinc and azelaic acid. Br J Dermatol. 1988 Nov;119(5):627-32. [PubMed:3207614 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Sterol 5-alpha reductase activity
Specific Function:
Converts testosterone (T) into 5-alpha-dihydrotestosterone (DHT) and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology.
Gene Name:
SRD5A2
Uniprot ID:
P31213
Molecular Weight:
28393.015 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Stamatiadis D, Bulteau-Portois MC, Mowszowicz I: Inhibition of 5 alpha-reductase activity in human skin by zinc and azelaic acid. Br J Dermatol. 1988 Nov;119(5):627-32. [PubMed:3207614 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Protein homodimerization activity
Specific Function:
This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the rate-limiting conversions of tyrosine to DOPA, DOPA to DOPA-quinone and possibly 5,6-dihydroxyindole to indole-5,6 quinone.
Gene Name:
TYR
Uniprot ID:
P14679
Molecular Weight:
60392.69 Da
References
  1. Schallreuter KU, Wood JW: A possible mechanism of action for azelaic acid in the human epidermis. Arch Dermatol Res. 1990;282(3):168-71. [PubMed:2114832 ]
  2. Nazzaro-Porro M: Azelaic acid. J Am Acad Dermatol. 1987 Dec;17(6):1033-41. [PubMed:2963038 ]
  3. Picardo M, Passi S, Sirianni MC, Fiorilli M, Russo GD, Cortesi E, Barile G, Breathnach AS, Nazzaro-Porro M: Activity of azelaic acid on cultures of lymphoma- and leukemia-derived cell lines, normal resting and stimulated lymphocytes and 3T3 fibroblasts. Biochem Pharmacol. 1985 May 15;34(10):1653-8. [PubMed:4004885 ]
  4. Nazzaro-Porro M, Passi S, Balus L, Breathnach A, Martin B, Morpurgo G: Effect of dicarboxylic acids on lentigo maligna. J Invest Dermatol. 1979 Jun;72(6):296-305. [PubMed:448162 ]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
yes
Actions
inhibitor
General Function:
Dna-directed dna polymerase activity
Specific Function:
In addition to polymerase activity, this DNA polymerase exhibits 3' to 5' and 5' to 3' exonuclease activity. It is able to utilize nicked circular duplex DNA as a template and can unwind the parental DNA strand from its template.
Gene Name:
polA
Uniprot ID:
P00582
Molecular Weight:
103117.145 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Galhaup I: Azelaic acid: mode of action at cellular and subcellular levels. Acta Derm Venereol Suppl (Stockh). 1989;143:75-82. [PubMed:2475996 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on July 30, 2016 02:27