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Identification
Name Azelaic Acid
Accession Number DB00548 (APRD00812, EXPT00598)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Anchoic acid
  • Azalaic Acid
  • Azelainic acid
  • Heptanedicarboxylic acid
  • Lepargylic acid
  • n-Nonanedioic acid
  • Nonanedioic acid
Brand names
  • Azelex
  • Emerox 1110
  • Emerox 1144
  • Emery's L-110
  • Finacea
  • Finevin
  • Skinoren
Brand name mixtures Not Available
Categories
  • Antineoplastic Agents
  • Dermatologic Agents
CAS number 123-99-9
Weight Average: 188.2209
Monoisotopic: 188.104859000
Chemical Formula C9H16O4
InChI Key InChIKey=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)
Plain Text
IUPAC Name
nonanedioic acid
SMILES
OC(=O)CCCCCCCC(O)=O
Plain Text
Mass Spec show (10.6 KB)
Taxonomy
Kingdom Organic
Classes
  • Dicarboxylic Acids
Substructures
  • Hydroxy Compounds
  • Acetates
  • Carboxylic Acids and Derivatives
  • Dicarboxylic Acids
Pharmacology
Indication For the topical treatment of mild-to-moderate inflammatory acne vulgaris.
Pharmacodynamics 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.
Mechanism of action The 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.
Absorption Approximately 4% of the topically applied azelaic acid is systemically absorbed.
Volume of distribution Not Available
Protein binding Not Available
Metabolism

Mainly excreted unchanged in the urine but undergoes some b-oxidation to shorter chain dicarboxylic acids.
Route of elimination Azelaic acid is mainly excreted unchanged in the urine, but undergoes some ß-oxidation to shorter chain dicarboxylic acids.
Half life The 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.
Clearance Not Available
Toxicity Oral LD50 in rat: >5 g/kg
Affected organisms
  • Various aerobic and anaerobic microorganisms
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Allergan inc
  • Intendis inc
Packagers
Dosage forms
Form Route Strength
Cream Topical
Prices
Unit description Cost Unit
Azelex 20% Cream 50 gm Tube 262.74 USD tube
Azelex 20% Cream 30 gm Tube 181.32 USD tube
Finacea 15% Gel 50 gm Tube 162.28 USD tube
Finacea plus kit 143.15 USD kit
Azelex 20% cream 5.21 USD g
Finacea 15% gel 2.86 USD g
Azelaic acid flakes 1.05 USD g
Patents
Country Patent Number Approved Expires
United States 6534070 1998-11-18 2018-11-18
Canada 2311128 2008-01-29 2018-11-18
Properties
State solid
Melting point 106.5 oC
Experimental Properties
Property Value Source
water solubility 2400 mg/L (20 oC) PhysProp
logP 1.7 PhysProp
logS -1.89 [ADME Research, USCD] PhysProp
pKa 4.55 Various sources
Predicted Properties
Property Value Source
water solubility 2.28e+00 g/l ALOGPS
logP 1.37 ALOGPS
logP 1.82 ChemAxon Molconvert
logS -1.92 ALOGPS
pKa 4.98 ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 74.60 ChemAxon Molconvert
rotatable bond count 8 ChemAxon Molconvert
refractivity 46.54 ChemAxon Molconvert
polarizability 20.50 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D03034 Link_out
KEGG Compound C08261 Link_out
PubChem Compound 2266 Link_out
PubChem Substance 46506284 Link_out
ChemSpider 2179 Link_out
ChEBI 48131 Link_out
ChEMBL 48131 Link_out
Therapeutic Targets Database DAP000889 Link_out
PharmGKB PA448516 Link_out
HET AZ1 Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic3/azelex.htm Link_out
Drugs.com http://www.drugs.com/cdi/azelaic-acid-cream.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/aze1043.shtml Link_out
ATC Codes
  • D10AX03
AHFS Codes Not Available
PDB Entries
FDA label show (388.7 KB)
MSDS show (72.9 KB)
Interactions
Drug Interactions
Drug Interaction
Food Interactions Not Available
Targets

1. Thioredoxin reductase

Pharmacological action: yes
Actions: inhibitor
Organism class: bacterial
UniProt ID: P66010 Link_out
Gene: trxB
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
  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

2. 3-oxo-5-beta-steroid 4-dehydrogenase

Pharmacological action: yes
Actions: inhibitor

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

Organism class: human
UniProt ID: P51857 Link_out
Gene: AKR1D1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

3. 3-oxo-5-alpha-steroid 4-dehydrogenase 2

Pharmacological action: yes
Actions: inhibitor

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

Organism class: human
UniProt ID: P31213 Link_out
Gene: SRD5A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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

4. Tyrosinase

Pharmacological action: yes
Actions: inhibitor

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

Organism class: human
UniProt ID: P14679 Link_out
Gene: TYR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  2. Nazzaro-Porro M: Azelaic acid. J Am Acad Dermatol. 1987 Dec;17(6):1033-41. Pubmed
  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
  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

5. DNA polymerase I

Pharmacological action: yes
Actions: inhibitor

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

Organism class: bacterial
UniProt ID: P00582 Link_out
Gene: polA
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Galhaup I: Azelaic acid: mode of action at cellular and subcellular levels. Acta Derm Venereol Suppl (Stockh). 1989;143:75-82. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on September 03, 2011 16:07

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.