Relevant Data

Food Additives Approved in the United States:


General Information

Chemical nameNonanedioic acid
CAS number123-99-9
COE number10079
Flavouring typesubstances
FL No.08.103
MixtureNo
Purity of the named substance at least 95% unless otherwise specified

From webgate.ec.europa.eu

Computed Descriptors

Download SDF
2D Structure
CID2266
IUPAC Namenonanedioic acid
InChIInChI=1S/C9H16O4/c10-8(11)6-4-2-1-3-5-7-9(12)13/h1-7H2,(H,10,11)(H,12,13)
InChI KeyBDJRBEYXGGNYIS-UHFFFAOYSA-N
Canonical SMILESC(CCCC(=O)O)CCCC(=O)O
Molecular FormulaC9H16O4
Wikipediaazelaic acid

From Pubchem


Computed Properties

Property Name Property Value
Molecular Weight188.223
Hydrogen Bond Donor Count2
Hydrogen Bond Acceptor Count4
Rotatable Bond Count8
Complexity147.0
CACTVS Substructure Key Fingerprint A A A D c e B w O A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A G g A A C A A A C A C A g A A A C A A A A g A I A A C Q C A A A A A A A A A A A A A E A A A A A A B I A A A A A Q A A E A A A A A A G I y K C A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A = =
Topological Polar Surface Area74.6
Monoisotopic Mass188.105
Exact Mass188.105
Compound Is CanonicalizedTrue
Formal Charge0
Heavy Atom Count13
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

From Pubchem


Food Additives Biosynthesis/Degradation


ADMET Predicted Profile --- Classification

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.7397
Human Intestinal AbsorptionHIA+0.5731
Caco-2 PermeabilityCaco2-0.6412
P-glycoprotein SubstrateNon-substrate0.6969
P-glycoprotein InhibitorNon-inhibitor0.9845
Non-inhibitor0.9229
Renal Organic Cation TransporterNon-inhibitor0.9359
Distribution
Subcellular localizationMitochondria0.8984
Metabolism
CYP450 2C9 SubstrateNon-substrate0.8447
CYP450 2D6 SubstrateNon-substrate0.9050
CYP450 3A4 SubstrateNon-substrate0.7534
CYP450 1A2 InhibitorNon-inhibitor0.9046
CYP450 2C9 InhibitorNon-inhibitor0.9390
CYP450 2D6 InhibitorNon-inhibitor0.9729
CYP450 2C19 InhibitorNon-inhibitor0.9762
CYP450 3A4 InhibitorNon-inhibitor0.9600
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.9927
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.9348
Non-inhibitor0.9602
AMES ToxicityNon AMES toxic0.9132
CarcinogensNon-carcinogens0.8382
Fish ToxicityHigh FHMT0.8783
Tetrahymena Pyriformis ToxicityHigh TPT0.6559
Honey Bee ToxicityHigh HBT0.6229
BiodegradationReady biodegradable0.8506
Acute Oral ToxicityIV0.6448
Carcinogenicity (Three-class)Non-required0.7514

From admetSAR


ADMET Predicted Profile --- Regression

Model Value Unit
Absorption
Aqueous solubility-1.8273LogS
Caco-2 Permeability0.3625LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity1.3577LD50, mol/kg
Fish Toxicity2.3886pLC50, mg/L
Tetrahymena Pyriformis Toxicity-0.3850pIGC50, ug/L

From admetSAR


Toxicity Profile

Route of ExposureApproximately 4% of the topically applied azelaic acid is systemically absorbed.
Mechanism of ToxicityThe 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 <i>Staphylococcus epidermidis</i> and <i>Propionibacterium acnes</i>. 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.
MetabolismMainly 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 нф-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.
Toxicity ValuesOral LD50 in rat: >5 g/kg
Lethal DoseNone
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Minimum Risk LevelNone
Health EffectsNone
TreatmentNone
Reference
  1. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762.[19212411 ]
  2. Hoffmann GF, Meier-Augenstein W, Stockler S, Surtees R, Rating D, Nyhan WL: Physiology and pathophysiology of organic acids in cerebrospinal fluid. J Inherit Metab Dis. 1993;16(4):648-69.[8412012 ]
  3. Mayer-da-Silva A, Gollnick H, Detmar M, Gassmuller J, Parry A, Muller R, Orfanos CE: Effects of azelaic acid on sebaceous gland, sebum excretion rate and keratinization pattern in human skin. An in vivo and in vitro study. Acta Derm Venereol Suppl (Stockh). 1989;143:20-30.[2475995 ]
  4. Hermanns JF, Petit L, Martalo O, Pierard-Franchimont C, Cauwenbergh G, Pierard GE: Unraveling the patterns of subclinical pheomelanin-enriched facial hyperpigmentation: effect of depigmenting agents. Dermatology. 2000;201(2):118-22.[11053913 ]
  5. Korman SH, Mandel H, Gutman A: Characteristic urine organic acid profile in peroxisomal biogenesis disorders. J Inherit Metab Dis. 2000 Jun;23(4):425-8.[10896310 ]
  6. Rocamora V, Puig L, Romani J, de Moragas JM: Amelanotic lentigo maligna melanoma: report of a case and review of the literature. Cutis. 1999 Jul;64(1):53-6.[10431675 ]
  7. Russell JJ: Topical therapy for acne. Am Fam Physician. 2000 Jan 15;61(2):357-66.[10670502 ]
  8. Webster G: Combination azelaic acid therapy for acne vulgaris. J Am Acad Dermatol. 2000 Aug;43(2 Pt 3):S47-50.[10898830 ]
  9. Del Rosso JQ: A status report on the medical management of rosacea: focus on topical therapies. Cutis. 2002 Nov;70(5):271-5.[12469780 ]
  10. Liao DC: Management of acne. J Fam Pract. 2003 Jan;52(1):43-51.[12540312 ]
  11. Del Rosso JQ: Medical treatment of rosacea with emphasis on topical therapies. Expert Opin Pharmacother. 2004 Jan;5(1):5-13.[14680431 ]
  12. Wolf JE Jr: The role of topical metronidazole in the treatment of rosacea. Cutis. 2004 Jan;73(1 Suppl):19-28.[14959942 ]
  13. Frampton JE, Wagstaff AJ: Azelaic acid 15% gel: in the treatment of papulopustular rosacea. Am J Clin Dermatol. 2004;5(1):57-64.[14979745 ]
  14. Halder RM, Richards GM: Management of dyschromias in ethnic skin. Dermatol Ther. 2004;17(2):151-7.[15113282 ]
  15. Halder RM, Richards GM: Topical agents used in the management of hyperpigmentation. Skin Therapy Lett. 2004 Jun-Jul;9(6):1-3.[15334278 ]
  16. Lindow KB: Rosacea. An overview of diagnosis and management. Adv Nurse Pract. 2004 Dec;12(12):27-32.[15615217 ]
  17. Cayce KA, McMichael AJ, Feldman SR: Hyperpigmentation: an overview of the common afflictions. Dermatol Nurs. 2004 Oct;16(5):401-6, 413-6; quiz 417.[15624705 ]
  18. Wolf JE Jr: Present and future rosacea therapy. Cutis. 2005 Mar;75(3 Suppl):4-7; discussion 33-6.[15810803 ]
  19. van Zuuren EJ, Graber MA: The rigor of trials evaluating Rosacea treatments. Cutis. 2005 Mar;75(3 Suppl):13-6; discussion 33-6.[15810805 ]
  20. Purdy S: Acne vulgaris. Clin Evid. 2005 Jun;(13):2038-59.[16135322 ]
  21. Roebuck HL: Face up to rosacea. Nurse Pract. 2005 Sep;30(9):24-30, 35; quiz 36-7.[16151303 ]
  22. Callender VD: Considerations for treating acne in ethnic skin. Cutis. 2005 Aug;76(2 Suppl):19-23.[16164153 ]
  23. Nally JB, Berson DS: Topical therapies for rosacea. J Drugs Dermatol. 2006 Jan;5(1):23-6.[16468288 ]
  24. Fleischer AB Jr: The evolution of azelaic acid. Cutis. 2006 Feb;77(2 Suppl):4-6.[16566281 ]
  25. Draelos ZD: The rationale for advancing the formulation of azelaic acid vehicles. Cutis. 2006 Feb;77(2 Suppl):7-11.[16566282 ]
  26. Elewski B, Thiboutot D: A clinical overview of azelaic acid. Cutis. 2006 Feb;77(2 Suppl):12-6.[16566283 ]
  27. Del Rosso JQ: The use of topical azelaic acid for common skin disorders other than inflammatory rosacea. Cutis. 2006 Feb;77(2 Suppl):22-4.[16566285 ]
  28. Worret WI, Fluhr JW: [Acne therapy with topical benzoyl peroxide, antibiotics and azelaic acid]. J Dtsch Dermatol Ges. 2006 Apr;4(4):293-300.[16638058 ]
  29. Liu RH, Smith MK, Basta SA, Farmer ER: Azelaic acid in the treatment of papulopustular rosacea: a systematic review of randomized controlled trials. Arch Dermatol. 2006 Aug;142(8):1047-52.[16924055 ]
  30. Goodman G: Managing acne vulgaris effectively. Aust Fam Physician. 2006 Sep;35(9):705-9.[16969442 ]
  31. Purdy S: Acne vulgaris. Clin Evid. 2006 Jun;(15):2183-201.[16973084 ]
  32. Gupta AK, Gover MD, Nouri K, Taylor S: The treatment of melasma: a review of clinical trials. J Am Acad Dermatol. 2006 Dec;55(6):1048-65. Epub 2006 Sep 28.[17097400 ]
  33. Fitton A, Goa KL: Azelaic acid. A review of its pharmacological properties and therapeutic efficacy in acne and hyperpigmentary skin disorders. Drugs. 1991 May;41(5):780-98.[1712709 ]
  34. van Zuuren EJ, Gupta AK, Gover MD, Graber M, Hollis S: Systematic review of rosacea treatments. J Am Acad Dermatol. 2007 Jan;56(1):107-15. Epub 2006 Nov 7.[17190628 ]
  35. Gupta AK, Gover MD: Azelaic acid (15% gel) in the treatment of acne rosacea. Int J Dermatol. 2007 May;46(5):533-8.[17472690 ]
  36. Nguyen QH, Bui TP: Azelaic acid: pharmacokinetic and pharmacodynamic properties and its therapeutic role in hyperpigmentary disorders and acne. Int J Dermatol. 1995 Feb;34(2):75-84.[7737781 ]
  37. Mackrides PS, Shaughnessy AF: Azelaic acid therapy for acne. Am Fam Physician. 1996 Dec;54(8):2457-9.[8961845 ]

From T3DB


Taxonomic Classification

KingdomOrganic compounds
SuperclassLipids and lipid-like molecules
ClassFatty Acyls
SubclassFatty acids and conjugates
Intermediate Tree NodesNot available
Direct ParentMedium-chain fatty acids
Alternative Parents
Molecular FrameworkAliphatic acyclic compounds
SubstituentsMedium-chain fatty acid - Dicarboxylic acid or derivatives - Carboxylic acid - Carboxylic acid derivative - Organic oxygen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Carbonyl group - Aliphatic acyclic compound
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.

From ClassyFire


Targets

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. 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. [3207614 ]
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. [3207614 ]
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. 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. [448162 ]
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 tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Thioredoxin-disulfide reductase activity
Gene Name:
trxB
Uniprot ID:
P66010
Molecular Weight:
33615.84 Da
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

From T3DB