T3DB: Azelaic Acid

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Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (4)XML

Targets (4)

Record Information

Version

2.0

Creation Date

2014-09-11 05:17:08 UTC

Update Date

2014-12-24 20:26:57 UTC

Accession Number

T3D4799

Identification

Common Name

Azelaic Acid

Class

Small Molecule

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.

Compound Type

Antineoplastic Agent
Dermatologic Agent
Drug
Food Toxin
Metabolite
Natural Compound
Organic Compound
Plant Toxin

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
1,7-Dicarboxyheptane
1,7-Heptanedicarboxylate
1,7-Heptanedicarboxylic acid
1,9-Nonanedioate
1,9-Nonanedioic acid
Acide azélaïque
Ácido azelaico
Acidum acelaicum
Acidum azelaicum
Acne-Derm
Acnean
Acnederm
Acnesafe
Aknoren
Ami
Anchoate
Anchoic acid
Arbonid
Azalaic acid
Azelaate
Azelaic acid
Azelaicacidtech
Azelainic acid
Azelainsaeure
Azelainsäure
Azelate
Azelex
Emerox 1110
Emerox 1144
Emery'S L-110
Finacea
Finevin
Heptanedicarboxylic acid
Lepargylate
Lepargylic acid
N-Nonanedioate
N-Nonanedioic acid
Nonandisaeure
Nonandisäure
Nonanedioate
Nonanedioic acid
Nonanedioic acid azelaic acid
Nonanedioic acid homopolymer
Poly(azelaic anhydride)
Polyazelaic anhydride
Skinorem
Skinoren
Zumilin

Chemical Formula

C₉H₁₆O₄

Average Molecular Mass

188.221 g/mol

Monoisotopic Mass

188.105 g/mol

CAS Registry Number

123-99-9

IUPAC Name

nonanedioic acid

Traditional Name

azelaic acid

SMILES

OC(=O)CCCCCCCC(O)=O

InChI Identifier

InChI=1S/C9H16O4/c10-8(11)6-4-2-1-3-5-7-9(12)13/h1-7H2,(H,10,11)(H,12,13)

InChI Key

InChIKey=BDJRBEYXGGNYIS-UHFFFAOYSA-N

Chemical Taxonomy

Description

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.

Kingdom

Organic compounds

Super Class

Lipids and lipid-like molecules

Class

Fatty Acyls

Sub Class

Fatty acids and conjugates

Direct Parent

Medium-chain fatty acids

Alternative Parents

Substituents

Medium-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

Molecular Framework

Aliphatic acyclic compounds

External Descriptors

alpha,omega-dicarboxylic acid (CHEBI:48131 )
Dicarboxylic acids (C08261 )
Dicarboxylic acids (LMFA01170054 )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Cytoplasm
Extracellular

Biofluid Locations

Not Available

Tissue Locations

Prostate
Skin

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	106.5°C
Boiling Point	286.5°C at 1.00E+02 mm Hg
Solubility	2400 mg/L (at 20°C)
LogP	1.57

Predicted Properties

Property	Value	Source
Water Solubility	2.28 g/L	ALOGPS
logP	1.37	ALOGPS
logP	1.82	ChemAxon
logS	-1.9	ALOGPS
pKa (Strongest Acidic)	4.15	ChemAxon
Physiological Charge	-2	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	74.6 Å²	ChemAxon
Rotatable Bond Count	8	ChemAxon
Refractivity	46.54 m³·mol⁻¹	ChemAxon
Polarizability	20.5 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
GC-MS	GC-MS Spectrum - GC-MS (2 TMS)	splash10-0v0r-4920000000-5a3ed693b1c4083f1f15	JSpectraViewer \| MoNA
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-0v0r-4920000000-5a3ed693b1c4083f1f15	JSpectraViewer \| MoNA
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-00mk-1910000000-83ba58dac4b0698643d0	JSpectraViewer \| MoNA
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-000f-9600000000-24638c458fa83f47c259	JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positive	splash10-00y0-9740000000-d157d08c3a7c87244190	JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive	Not Available	JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_2_1) - 70eV, Positive	Not Available	JSpectraViewer
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Negative (Annotated)	splash10-000i-0900000000-a118e433f0bd27a95b89	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Negative (Annotated)	splash10-006t-9600000000-93b3a375b722791cb5c9	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Negative (Annotated)	splash10-052k-9500000000-6b069f2fed947651b284	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negative	splash10-000i-0900000000-7980b5eadcca6ee1eadd	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negative	splash10-004i-0900000000-462585874f7661d40d5b	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negative	splash10-004j-4900000000-0f65eeeed8c8a6ff3cc9	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negative	splash10-0002-9300000000-d654ca3c764066f98358	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negative	splash10-0002-9000000000-60a08bb384f2b4cbfca8	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-000i-0900000000-7980b5eadcca6ee1eadd	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-004i-0900000000-462585874f7661d40d5b	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-004j-4900000000-0f65eeeed8c8a6ff3cc9	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-0002-9300000000-fcefbd80852c2625bc0e	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-0002-9000000000-60a08bb384f2b4cbfca8	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - Linear Ion Trap , negative	splash10-004i-0900000000-26216115e75cad833509	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - Linear Ion Trap , negative	splash10-004i-0900000000-7bef8272c481ea57a60b	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - Linear Ion Trap , negative	splash10-004i-0900000000-751bf479539d4bd2b5e1	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - Linear Ion Trap , negative	splash10-00di-0900000000-9a056a45b27896966bf9	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - Linear Ion Trap , negative	splash10-00di-0900000000-3155fd845eec8f32ce93	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - , negative	splash10-004r-0900000000-544110f97ebc0f97e15b	JSpectraViewer \| MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-00dr-0900000000-b1b7c1ab57d58a2405a8	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00g3-2900000000-d0ba7fbbe987efa4c818	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-05qd-9100000000-8d65a19b998d18ad08ac	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-000i-0900000000-a7edc3ac66d27685b9d1	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-00kr-1900000000-c56b9d972f88c58dc65b	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0a4l-9300000000-47cbefe19a788d7f36b9	JSpectraViewer
MS	Mass Spectrum (Electron Ionization)	splash10-06rx-9100000000-6db2acb47ad4c6163063	JSpectraViewer \| MoNA
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
2D NMR	[1H,13C] 2D NMR Spectrum	Not Available	JSpectraViewer

Toxicity Profile

Route of Exposure

Approximately 4% of the topically applied azelaic acid is systemically absorbed.

Mechanism of Toxicity

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.

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 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 Values

Oral LD50 in rat: >5 g/kg

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

For the topical treatment of mild-to-moderate inflammatory acne vulgaris.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

48131

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

AZ1

ACToR ID

Not Available

Wikipedia Link

Nonanedioic acid

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.

MSDS

Link

General References

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 ]
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 ]
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 ]
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 ]
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 ]
Russell JJ: Topical therapy for acne. Am Fam Physician. 2000 Jan 15;61(2):357-66. [10670502 ]
Webster G: Combination azelaic acid therapy for acne vulgaris. J Am Acad Dermatol. 2000 Aug;43(2 Pt 3):S47-50. [10898830 ]
Del Rosso JQ: A status report on the medical management of rosacea: focus on topical therapies. Cutis. 2002 Nov;70(5):271-5. [12469780 ]
Liao DC: Management of acne. J Fam Pract. 2003 Jan;52(1):43-51. [12540312 ]
Del Rosso JQ: Medical treatment of rosacea with emphasis on topical therapies. Expert Opin Pharmacother. 2004 Jan;5(1):5-13. [14680431 ]
Wolf JE Jr: The role of topical metronidazole in the treatment of rosacea. Cutis. 2004 Jan;73(1 Suppl):19-28. [14959942 ]
Frampton JE, Wagstaff AJ: Azelaic acid 15% gel: in the treatment of papulopustular rosacea. Am J Clin Dermatol. 2004;5(1):57-64. [14979745 ]
Halder RM, Richards GM: Management of dyschromias in ethnic skin. Dermatol Ther. 2004;17(2):151-7. [15113282 ]
Halder RM, Richards GM: Topical agents used in the management of hyperpigmentation. Skin Therapy Lett. 2004 Jun-Jul;9(6):1-3. [15334278 ]
Lindow KB: Rosacea. An overview of diagnosis and management. Adv Nurse Pract. 2004 Dec;12(12):27-32. [15615217 ]
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 ]
Wolf JE Jr: Present and future rosacea therapy. Cutis. 2005 Mar;75(3 Suppl):4-7; discussion 33-6. [15810803 ]
van Zuuren EJ, Graber MA: The rigor of trials evaluating Rosacea treatments. Cutis. 2005 Mar;75(3 Suppl):13-6; discussion 33-6. [15810805 ]
Purdy S: Acne vulgaris. Clin Evid. 2005 Jun;(13):2038-59. [16135322 ]
Roebuck HL: Face up to rosacea. Nurse Pract. 2005 Sep;30(9):24-30, 35; quiz 36-7. [16151303 ]
Callender VD: Considerations for treating acne in ethnic skin. Cutis. 2005 Aug;76(2 Suppl):19-23. [16164153 ]
Nally JB, Berson DS: Topical therapies for rosacea. J Drugs Dermatol. 2006 Jan;5(1):23-6. [16468288 ]
Fleischer AB Jr: The evolution of azelaic acid. Cutis. 2006 Feb;77(2 Suppl):4-6. [16566281 ]
Draelos ZD: The rationale for advancing the formulation of azelaic acid vehicles. Cutis. 2006 Feb;77(2 Suppl):7-11. [16566282 ]
Elewski B, Thiboutot D: A clinical overview of azelaic acid. Cutis. 2006 Feb;77(2 Suppl):12-6. [16566283 ]
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 ]
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 ]
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 ]
Goodman G: Managing acne vulgaris effectively. Aust Fam Physician. 2006 Sep;35(9):705-9. [16969442 ]
Purdy S: Acne vulgaris. Clin Evid. 2006 Jun;(15):2183-201. [16973084 ]
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 ]
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 ]
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 ]
Gupta AK, Gover MD: Azelaic acid (15% gel) in the treatment of acne rosacea. Int J Dermatol. 2007 May;46(5):533-8. [17472690 ]
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 ]
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 ]
Mackrides PS, Shaughnessy AF: Azelaic acid therapy for acne. Am Fam Physician. 1996 Dec;54(8):2457-9. [8961845 ]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Tyrosinase

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

Schallreuter KU, Wood JW: A possible mechanism of action for azelaic acid in the human epidermis. Arch Dermatol Res. 1990;282(3):168-71. [2114832 ]
Nazzaro-Porro M: Azelaic acid. J Am Acad Dermatol. 1987 Dec;17(6):1033-41. [2963038 ]
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. [4004885 ]
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 ]

Target Details

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

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

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
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. [17016423 ]
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 ]

Target Details

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

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

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 ]

Target Details

4. Estrogen receptor

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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	8.63 uM	Tox21_ERa_LUC_BG1_Agonist	Tox21/NCGC

References

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 ]

Azelaic Acid (T3D4799)

Structure for T3D4799: Azelaic Acid

Targets

References

References

References

Binding/Activity Constants

References