T3DB: Aspirin

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (18)XML

Targets (18)

Record Information

Version

2.0

Creation Date

2009-07-21 20:28:00 UTC

Update Date

2014-12-24 20:25:53 UTC

Accession Number

T3D2936

Identification

Common Name

Aspirin

Class

Small Molecule

Description

Acetylsalicylic acid (acetosal) or aspirin is only found in individuals who have consumed this drug. Acetylsalicylic acid is a drug in the family of salicylates, often used as an analgesic (against minor pains and aches), antipyretic (against fever), and anti-inflammatory. It has also an anticoagulant effect and is used in long-term low-doses to prevent heart attacks and cancer. It was isolated from meadowsweet (Filipendula ulmaria, formerly classified as Spiraea ulmaria) by German researchers in 1839. While their extract was somewhat effective, it also caused digestive problems such as irritated stomach and diarrhoea, and even death when consumed in high doses. In 1853, a French chemist named Charles Frederic Gerhardt neutralized salicylic acid by buffering it with sodium (sodium salicylate) and acetyl chloride, creating acetosalicylic anhydride. Gerhardt's product worked, but he had no desire to market it and abandoned his discovery. In 1897, researcher Arthur Eichengrun and Felix Hoffmann, a research assistant at Friedrich Bayer & Co. in Germany, derivatized one of the hydroxyl functional groups in salicylic acid with an acetyl group (forming the acetyl ester), which greatly reduced the negative effects. This was the first synthetic drug, not a copy of something that existed in nature, and the start of the pharmaceuticals industry. The name 'aspirin' is composed of a- (from the acetyl group) -spir- (from the plant genus Spiraea) and -in (a common ending for drugs at the time). It has also been stated that the name originated by another means. As referring to AcetylSalicylic and 'pir' in reference to one of the scientists who was able to isolate it in crystalline form, Raffaele Piria. Finally 'in' due to the same reasons as stated above. Salicylic acid (which is a naturally occurring substance found in many plants) can be acetylated using acetic anhydride, yielding aspirin and acetic acid as a byproduct. It is a common experiment performed in organic chemistry labs, and generally tends to produce low yields due to the relative difficulty of its extraction from an aqueous state. The trick to getting the reaction to work is to acidify with phosphoric acid and heat the reagents under reflux with a boiling water bath for between 40 minutes and an hour. Aspirin acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5).

Compound Type

Anti-Inflammatory Agent, Non-Steroidal
Anticoagulant
Antipyretic
Cyclooxygenase Inhibitor
Drug
Ester
Fibrinolytic Agent
Food Toxin
Metabolite
Organic Compound
Platelet Aggregation Inhibitor
Salicylate
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
2-(Acetyloxy)benzoate
2-(Acetyloxy)benzoic acid
2-Acetoxybenzenecarboxylic acid
2-Acetoxybenzoate
2-Acetoxybenzoic acid
2-Carboxyphenyl acetate
Acenterine
Acetard
Aceticyl
Acetol
Acetonyl
Acetophen
Acetosal
Acetosalin
Acetylin
Acetylsalicylate
Acetylsalicylic acid
Acetylsalicylsaeure
Acetyonyl
Acetysal
Acetysalicylic acid
Acide 2-(acetyloxy)benzoique
Acide acétylsalicylique
ácido acetilsalicílico
Acidum acetylsalicylicum
Acylpyrin
Adiro
ASA
Asatard
Aspergum
Aspirdrops
Aspro
Azetylsalizylsaeure
Azetylsalizylsäure
Bayer Aspirin
Benaspir
Bialpirinia
Bufferin
Caprin
Cardioaspirina
Easprin
Ecolen
Ecotrin
Empirin
Endosprin
Endydol
Entrophen
Nu-seals
O-(Acetyloxy)benzoate
O-(Acetyloxy)benzoic acid
O-Acetoxybenzoate
O-Acetoxybenzoic acid
O-Acetylsalicylic acid
O-Carboxyphenyl acetate
Persistin
Pharmacin
Polopiryna
Premaspin
Rheumintabletten
Rhodine
Rhonal
Salcetogen
Saletin
Salicylic acid acetate
Salospir
Solprin
Solprin acid
Solpyron
St. Joseph Aspirin for Adults
Tasprin
Temperal
Toldex
Triaminicin

Chemical Formula

C₉H₈O₄

Average Molecular Mass

180.157 g/mol

Monoisotopic Mass

180.042 g/mol

CAS Registry Number

50-78-2

IUPAC Name

2-(acetyloxy)benzoic acid

Traditional Name

aspirin

SMILES

CC(=O)OC1=CC=CC=C1C(O)=O

InChI Identifier

InChI=1S/C9H8O4/c1-6(10)13-8-5-3-2-4-7(8)9(11)12/h2-5H,1H3,(H,11,12)

InChI Key

InChIKey=BSYNRYMUTXBXSQ-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as acylsalicylic acids. These are o-acylated derivatives of salicylic acid.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Benzoic acids and derivatives

Direct Parent

Acylsalicylic acids

Alternative Parents

Substituents

Acylsalicylic acid
Phenol ester
Benzoic acid
Phenoxy compound
Benzoyl
Dicarboxylic acid or derivatives
Carboxylic acid ester
Carboxylic acid
Carboxylic acid derivative
Organic oxygen compound
Organic oxide
Hydrocarbon derivative
Organooxygen compound
Carbonyl group
Aromatic homomonocyclic compound

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

salicylates (CHEBI:15365 )
acetate ester (CHEBI:15365 )
benzoic acids (CHEBI:15365 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular

Biofluid Locations

Not Available

Tissue Locations

Platelet

Pathways

Name	SMPDB Link	KEGG Link
Acetylsalicylic Acid Pathway	Not Available	Not Available

Applications

Biological Roles

Chemical Roles

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	135°C
Boiling Point	140°C
Solubility	4600 mg/L (at 25°C)
LogP	1.19

Predicted Properties

Property	Value	Source
Water Solubility	1.46 g/L	ALOGPS
logP	1.43	ALOGPS
logP	1.24	ChemAxon
logS	-2.1	ALOGPS
pKa (Strongest Acidic)	3.41	ChemAxon
pKa (Strongest Basic)	-7.1	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	63.6 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	44.45 m³·mol⁻¹	ChemAxon
Polarizability	17.1 Å³	ChemAxon
Number of Rings	1	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	Deposition Date	View
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-014l-2960000000-ffcb8d28ab7e460b0da8	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (1 TMS)	splash10-006w-2910000000-910e8ce2493a05870b33	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-00dl-9400000000-64327d3bef0063cf4fe1	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - CI-B (Non-derivatized)	splash10-00di-0900000000-113943b65024522c1712	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-014i-1590000000-7890c99ca2b0e2c4ff19	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-014l-2960000000-ffcb8d28ab7e460b0da8	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-006w-2910000000-910e8ce2493a05870b33	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-006w-2900000000-253eb678a85f77d4ba61	2017-09-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-000f-8900000000-760033c820b78b9452ed	2017-08-28	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-00dl-9830000000-b3fcef47ab2b2ba0e7d1	2017-10-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-00kr-6900000000-324f46e8def1652ed4bf	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-000i-9000000000-cdf64eaf75083da6f355	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-000i-9000000000-ee75806b6fb8a38fd697	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - EI-B (Unknown) , Positive	splash10-00dl-9400000000-64327d3bef0063cf4fe1	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - CI-B (Unknown) , Positive	splash10-00di-0900000000-113943b65024522c1712	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-000i-1900000000-bc50013edb10656e0aa4	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-000i-2900000000-8c55c1f8d7cb7f247a5d	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-000l-9700000000-d475fd0478daf18a419a	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-0006-9100000000-3daaf3c8697e17e67869	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-0006-9000000000-ee876bcdd1a5c7c229a0	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-0006-9000000000-cd4e1f8fe0a2bbc869f9	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-0006-9000000000-4dca49851b5b9fd03d1a	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-00kf-9000000000-4611655c6aff89d706eb	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-014l-9000000000-4d636e2d7318b857528d	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-01ot-0900000000-1256ca04e4244fbc4a64	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-01ot-0900000000-2cae7e19320bfa1a03a0	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-01ot-0900000000-42f69c49b256900b7524	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-01ot-0900000000-4860d5cbeeb9c31311ec	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-006t-3900000000-cc185048e2a1bcc52124	2017-09-14	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-001i-0900000000-96fcc874bfbf44a6ce6c	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0019-1900000000-8ea2ab1846fc78de4262	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0fkc-9700000000-53fc1f45243a05bf1c17	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-002r-1900000000-421bc1739eeb6dced80a	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-000l-4900000000-1c7dec3a4993a5b23cd8	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9100000000-81a6114ec99ac0f0f393	2017-07-26	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-00dl-6900000000-74f8a29aa18d0c3afe98	2014-09-20	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, H₂O, experimental)	Not Available	2012-12-04	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, CDCl₃, experimental)	Not Available	2014-09-20	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 50.18 MHz, CDCl₃, experimental)	Not Available	2014-09-23	View Spectrum
2D NMR	[¹H, ¹³C]-HSQC NMR Spectrum (2D, 600 MHz, H₂O, experimental)	Not Available	2012-12-05	View Spectrum

Toxicity Profile

Route of Exposure

Absorption is generally rapid and complete following oral administration but may vary according to specific salicylate used, dosage form, and other factors such as tablet dissolution rate and gastric or intraluminal pH.

Mechanism of Toxicity

The analgesic, antipyretic, and anti-inflammatory effects of acetylsalicylic acid are due to actions by both the acetyl and the salicylate portions of the intact molecule as well as by the active salicylate metabolite. Acetylsalicylic acid directly and irreversibly inhibits the activity of both types of cyclooxygenase (COX-1 and COX-2) to decrease the formation of precursors of prostaglandins and thromboxanes from arachidonic acid. This makes acetylsalicylic acid different from other NSAIDS (such as diclofenac and ibuprofen) which are reversible inhibitors. Salicylate may competitively inhibit prostaglandin formation. Acetylsalicylic acid's antirheumatic (nonsteroidal anti-inflammatory) actions are a result of its analgesic and anti-inflammatory mechanisms; the therapeutic effects are not due to pituitary-adrenal stimulation. The platelet aggregation-inhibiting effect of acetylsalicylic acid specifically involves the compound's ability to act as an acetyl donor to cyclooxygenase; the nonacetylated salicylates have no clinically significant effect on platelet aggregation. Irreversible acetylation renders cyclooxygenase inactive, thereby preventing the formation of the aggregating agent thromboxane A2 in platelets. Since platelets lack the ability to synthesize new proteins, the effects persist for the life of the exposed platelets (7-10 days). Acetylsalicylic acid may also inhibit production of the platelet aggregation inhibitor, prostacyclin (prostaglandin I2), by blood vessel endothelial cells; however, inhibition prostacyclin production is not permanent as endothelial cells can produce more cyclooxygenase to replace the non-functional enzyme.

Metabolism

Acetylsalicylic acid is rapidly hydrolyzed primarily in the liver to salicylic acid, which is conjugated with glycine (forming salicyluric acid) and glucuronic acid and excreted largely in the urine. Half Life: The plasma half-life is approximately 15 minutes; that for salicylate lengthens as the dose increases: doses of 300 to 650 mg have a half-life of 3.1 to 3.2 hours; with doses of 1 gram, the half-life is increased to 5 hours and with 2 grams it is increased to about 9 hours.

Toxicity Values

LD50: 250 mg/kg (Oral, Mouse) (6) LD50: 1010 mg/kg (Oral, Rabbit) (6) LD50: 200 mg/kg (Oral, Rat) (6)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

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

Uses/Sources

For use in the temporary relief of various forms of pain, inflammation associated with various conditions (including rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, and ankylosing spondylitis), and is also used to reduce the risk of death and/or nonfatal myocardial infarction in patients with a previous infarction or unstable angina pectoris.

Minimum Risk Level

Not Available

Health Effects

Might increase the risk of gastrointestinal bleeding; large doses of salicylate, a metabolite of aspirin, have been proposed to cause tinnitus; Reye's syndrome, a severe illness characterized by acute encephalopathy and fatty liver, can occur when children or adolescents are given aspirin for a fever or other illnesses or infections. [Wikipedia]

Symptoms

Effects of overdose include: tinnitus, abdominal pain, hypokalemia, hypoglycemia, pyrexia, hyperventilation, dysrhythmia, hypotension, hallucination, renal failure, confusion, seizure, coma, and death.

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

15365

BioCyc ID

CPD-524

CTD ID

Not Available

Stitch ID

Aspirin

PDB ID

AIN

ACToR ID

109

Wikipedia Link

Aspirin

References

Synthesis Reference

Marino Gobetti, Guido Vandoni, “Acetylsalicylic acid thioesters, a process for their preparation and pharmaceutical compositions containing them.” U.S. Patent US4563443, issued March, 1981.

MSDS

Link

General References

Macdonald S: Aspirin use to be banned in under 16 year olds. BMJ. 2002 Nov 2;325(7371):988. [12411346 ]
Sneader W: The discovery of aspirin: a reappraisal. BMJ. 2000 Dec 23-30;321(7276):1591-4. [11124191 ]
Aukerman G, Knutson D, Miser WF: Management of the acute migraine headache. Am Fam Physician. 2002 Dec 1;66(11):2123-30. [12484694 ]
Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet. 1988 Aug 13;2(8607):349-60. [2899772 ]
Dorsch MP, Lee JS, Lynch DR, Dunn SP, Rodgers JE, Schwartz T, Colby E, Montague D, Smyth SS: Aspirin resistance in patients with stable coronary artery disease with and without a history of myocardial infarction. Ann Pharmacother. 2007 May;41(5):737-41. Epub 2007 Apr 24. [17456544 ]
Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
Frelinger AL 3rd, Furman MI, Linden MD, Li Y, Fox ML, Barnard MR, Michelson AD: Residual arachidonic acid-induced platelet activation via an adenosine diphosphate-dependent but cyclooxygenase-1- and cyclooxygenase-2-independent pathway: a 700-patient study of aspirin resistance. Circulation. 2006 Jun 27;113(25):2888-96. Epub 2006 Jun 19. [16785341 ]
Eikelboom J, Feldman M, Mehta SR, Michelson AD, Oates JA, Topol E: Aspirin resistance and its implications in clinical practice. MedGenMed. 2005 Jul 11;7(3):76. [16369302 ]
Konrad CJ, Schuepfer GK, Gerber H, Rukwied R, Schmelz M, Schley M: Duration of effects of aspirin on platelet function in healthy volunteers: an analysis using the PFA-100. J Clin Anesth. 2006 Feb;18(1):12-7. [16517326 ]
Faraday N, Becker DM, Yanek LR, Herrera-Galeano JE, Segal JB, Moy TF, Bray PF, Becker LC: Relation between atherosclerosis risk factors and aspirin resistance in a primary prevention population. Am J Cardiol. 2006 Sep 15;98(6):774-9. Epub 2006 Jul 28. [16950183 ]
Lee SH, Rhim T, Choi YS, Min JW, Kim SH, Cho SY, Paik YK, Park CS: Complement C3a and C4a increased in plasma of patients with aspirin-induced asthma. Am J Respir Crit Care Med. 2006 Feb 15;173(4):370-8. Epub 2005 Nov 17. [16293803 ]
Perneby C, Wallen NH, Rooney C, Fitzgerald D, Hjemdahl P: Dose- and time-dependent antiplatelet effects of aspirin. Thromb Haemost. 2006 Apr;95(4):652-8. [16601836 ]
Maree AO, Curtin RJ, Chubb A, Dolan C, Cox D, O'Brien J, Crean P, Shields DC, Fitzgerald DJ: Cyclooxygenase-1 haplotype modulates platelet response to aspirin. J Thromb Haemost. 2005 Oct;3(10):2340-5. Epub 2005 Sep 9. [16150050 ]
Satoh K, Ozaki Y: [Attempts for aspirin monitoring with a new assay system, Ultegra Rapid Platelet Function Assay (RPFA), based on turbidimetric platelet agglutination of whole blood samples]. Rinsho Byori. 2006 Jun;54(6):576-82. [16872006 ]
Eikelboom JW, Hankey GJ, Thom J, Claxton A, Yi Q, Gilmore G, Staton J, Barden A, Norman PE: Enhanced antiplatelet effect of clopidogrel in patients whose platelets are least inhibited by aspirin: a randomized crossover trial. J Thromb Haemost. 2005 Dec;3(12):2649-55. [16359503 ]
Cornelissen J, Kirtland S, Lim E, Goddard M, Bellm S, Sheridan K, Large S, Vuylsteke A: Biological efficacy of low against medium dose aspirin regimen after coronary surgery: analysis of platelet function. Thromb Haemost. 2006 Mar;95(3):476-82. [16525576 ]
Eliasson B, Cederholm J, Nilsson P, Gudbjornsdottir S: The gap between guidelines and reality: Type 2 diabetes in a National Diabetes Register 1996-2003. Diabet Med. 2005 Oct;22(10):1420-6. [16176206 ]
Zailaie MZ: Aspirin reduces serum anti-melanocyte antibodies and soluble interleukin-2 receptors in vitiligo patients. Saudi Med J. 2005 Jul;26(7):1085-91. [16047057 ]
Aktas B, Pozgajova M, Bergmeier W, Sunnarborg S, Offermanns S, Lee D, Wagner DD, Nieswandt B: Aspirin induces platelet receptor shedding via ADAM17 (TACE). J Biol Chem. 2005 Dec 2;280(48):39716-22. Epub 2005 Sep 22. [16179345 ]
Maree AO, Curtin RJ, Dooley M, Conroy RM, Crean P, Cox D, Fitzgerald DJ: Platelet response to low-dose enteric-coated aspirin in patients with stable cardiovascular disease. J Am Coll Cardiol. 2005 Oct 4;46(7):1258-63. [16198840 ]
Lev EI, Patel RT, Maresh KJ, Guthikonda S, Granada J, DeLao T, Bray PF, Kleiman NS: Aspirin and clopidogrel drug response in patients undergoing percutaneous coronary intervention: the role of dual drug resistance. J Am Coll Cardiol. 2006 Jan 3;47(1):27-33. Epub 2005 Dec 9. [16386660 ]
Sun W, Gerhardinger C, Dagher Z, Hoehn T, Lorenzi M: Aspirin at low-intermediate concentrations protects retinal vessels in experimental diabetic retinopathy through non-platelet-mediated effects. Diabetes. 2005 Dec;54(12):3418-26. [16306357 ]
Markuszewski L, Rosiak M, Golanski J, Rysz J, Spychalska M, Watala C: Reduced blood platelet sensitivity to aspirin in coronary artery disease: are dyslipidaemia and inflammatory states possible factors predisposing to sub-optimal platelet response to aspirin? Basic Clin Pharmacol Toxicol. 2006 May;98(5):503-9. [16635110 ]
Tantry US, Bliden KP, Gurbel PA: Overestimation of platelet aspirin resistance detection by thrombelastograph platelet mapping and validation by conventional aggregometry using arachidonic acid stimulation. J Am Coll Cardiol. 2005 Nov 1;46(9):1705-9. Epub 2005 Oct 10. [16256872 ]
Hermida RC, Ayala DE, Calvo C, Lopez JE, Mojon A, Rodriguez M, Fernandez JR: Differing administration time-dependent effects of aspirin on blood pressure in dipper and non-dipper hypertensives. Hypertension. 2005 Oct;46(4):1060-8. Epub 2005 Aug 8. [16087788 ]
Savion N, Varon D: Impact--the cone and plate(let) analyzer: testing platelet function and anti-platelet drug response. Pathophysiol Haemost Thromb. 2006;35(1-2):83-8. [16855351 ]
Drugs.com [Link]

Gene Regulation

Up-Regulated Genes

Gene	Gene Symbol	Gene ID	Interaction	Chromosome	Details

Down-Regulated Genes

Gene	Gene Symbol	Gene ID	Interaction	Chromosome	Details

Targets

Target Details

1. Prostaglandin G/H synthase 2

General Function:: Prostaglandin-endoperoxide synthase activity
Specific Function:: Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, phenotypic changes, resistance to apoptosis and tumor angiogenesis. In cancer cells, PTGS2 is a key step in the production of prostaglandin E2 (PGE2), which plays important roles in modulating motility, proliferation and resistance to apoptosis.
Gene Name:: PTGS2
Uniprot ID:: P35354
Molecular Weight:: 68995.625 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	>10 uM	Not Available	BindingDB 22360
IC50	2.4 uM	Not Available	BindingDB 22360
IC50	19.8 uM	Not Available	BindingDB 22360
IC50	62.5 uM	Not Available	BindingDB 22360
IC50	100 uM	Not Available	BindingDB 22360
IC50	710 uM	Not Available	BindingDB 22360
IC50	1000 uM	Not Available	BindingDB 22360
IC50	1050 uM	Not Available	BindingDB 22360
IC50	1413.3 uM	Not Available	BindingDB 22360
IC50	18000 uM	Not Available	BindingDB 22360
IC50	>400 uM	Not Available	BindingDB 22360

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Brzozowski T, Konturek PC, Sliwowski Z, Kwiecien S, Drozdowicz D, Pawlik M, Mach K, Konturek SJ, Pawlik WW: Interaction of nonsteroidal anti-inflammatory drugs (NSAID) with Helicobacter pylori in the stomach of humans and experimental animals. J Physiol Pharmacol. 2006 Sep;57 Suppl 3:67-79. [17033106 ]
Wang HJ, Liu XJ, Yang KX, Luo FM, Lou JY, Peng ZL: [Effects of nonsteroidal anti-inflammatory drug celecoxib on expression of cyclooxygenase-2 (COX-2) in ovarian carcinoma cell]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2006 Sep;37(5):757-60. [17037745 ]
Shen J, Gammon MD, Terry MB, Teitelbaum SL, Neugut AI, Santella RM: Genetic polymorphisms in the cyclooxygenase-2 gene, use of nonsteroidal anti-inflammatory drugs, and breast cancer risk. Breast Cancer Res. 2006;8(6):R71. [17181859 ]
Nakano M, Denda N, Matsumoto M, Kawamura M, Kawakubo Y, Hatanaka K, Hiramoto Y, Sato Y, Noshiro M, Harada Y: Interaction between cyclooxygenase (COX)-1- and COX-2-products modulates COX-2 expression in the late phase of acute inflammation. Eur J Pharmacol. 2007 Mar 22;559(2-3):210-8. Epub 2006 Dec 16. [17258197 ]
Hall MN, Campos H, Li H, Sesso HD, Stampfer MJ, Willett WC, Ma J: Blood levels of long-chain polyunsaturated fatty acids, aspirin, and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2007 Feb;16(2):314-21. [17301265 ]
Rao PN, Chen QH, Knaus EE: Synthesis and structure-activity relationship studies of 1,3-diarylprop-2-yn-1-ones: dual inhibitors of cyclooxygenases and lipoxygenases. J Med Chem. 2006 Mar 9;49(5):1668-83. [16509583 ]
Abdellatif KR, Chowdhury MA, Dong Y, Das D, Yu G, Velazquez C, Suresh MR, Knaus EE: Diazen-1-ium-1,2-diolated nitric oxide donor ester prodrugs of 5-(4-carboxymethylphenyl)-1-(4-methanesulfonylphenyl)-3-trifluoromethyl-1H-pyrazo le and its aminosulfonyl analog: Synthesis, biological evaluation and nitric oxide release studies. Bioorg Med Chem. 2009 Jul 15;17(14):5182-8. doi: 10.1016/j.bmc.2009.05.046. Epub 2009 May 27. [19500994 ]
Chowdhury MA, Abdellatif KR, Dong Y, Das D, Yu G, Velazquez CA, Suresh MR, Knaus EE: Synthesis and biological evaluation of salicylic acid and N-acetyl-2-carboxybenzenesulfonamide regioisomers possessing a N-difluoromethyl-1,2-dihydropyrid-2-one pharmacophore: dual inhibitors of cyclooxygenases and 5-lipoxygenase with anti-inflammatory activity. Bioorg Med Chem Lett. 2009 Dec 15;19(24):6855-61. doi: 10.1016/j.bmcl.2009.10.083. Epub 2009 Oct 23. [19884005 ]
Chowdhury MA, Abdellatif KR, Dong Y, Yu G, Huang Z, Rahman M, Das D, Velazquez CA, Suresh MR, Knaus EE: Celecoxib analogs possessing a N-(4-nitrooxybutyl)piperidin-4-yl or N-(4-nitrooxybutyl)-1,2,3,6-tetrahydropyridin-4-yl nitric oxide donor moiety: synthesis, biological evaluation and nitric oxide release studies. Bioorg Med Chem Lett. 2010 Feb 15;20(4):1324-9. doi: 10.1016/j.bmcl.2010.01.014. Epub 2010 Jan 11. [20097072 ]
Abdellatif KR, Chowdhury MA, Velazquez CA, Huang Z, Dong Y, Das D, Yu G, Suresh MR, Knaus EE: Celecoxib prodrugs possessing a diazen-1-ium-1,2-diolate nitric oxide donor moiety: synthesis, biological evaluation and nitric oxide release studies. Bioorg Med Chem Lett. 2010 Aug 1;20(15):4544-9. doi: 10.1016/j.bmcl.2010.06.022. Epub 2010 Jun 8. [20576432 ]
Jain S, Tran S, El Gendy MA, Kashfi K, Jurasz P, Velazquez-Martinez CA: Nitric oxide release is not required to decrease the ulcerogenic profile of nonsteroidal anti-inflammatory drugs. J Med Chem. 2012 Jan 26;55(2):688-96. doi: 10.1021/jm200973j. Epub 2012 Jan 10. [22148253 ]
Kaur J, Bhardwaj A, Huang Z, Knaus EE: N-1 and C-3 substituted indole Schiff bases as selective COX-2 inhibitors: synthesis and biological evaluation. Bioorg Med Chem Lett. 2012 Mar 15;22(6):2154-9. doi: 10.1016/j.bmcl.2012.01.130. Epub 2012 Feb 6. [22361134 ]
Bhardwaj A, Kaur J, Sharma SK, Huang Z, Wuest F, Knaus EE: Hybrid fluorescent conjugates of COX-2 inhibitors: search for a COX-2 isozyme imaging cancer biomarker. Bioorg Med Chem Lett. 2013 Jan 1;23(1):163-8. doi: 10.1016/j.bmcl.2012.10.131. Epub 2012 Nov 9. [23200247 ]
Boonphong S, Puangsombat P, Baramee A, Mahidol C, Ruchirawat S, Kittakoop P: Bioactive compounds from Bauhinia purpurea possessing antimalarial, antimycobacterial, antifungal, anti-inflammatory, and cytotoxic activities. J Nat Prod. 2007 May;70(5):795-801. Epub 2007 May 5. [17480099 ]
Kalgutkar AS, Kozak KR, Crews BC, Hochgesang GP Jr, Marnett LJ: Covalent modification of cyclooxygenase-2 (COX-2) by 2-acetoxyphenyl alkyl sulfides, a new class of selective COX-2 inactivators. J Med Chem. 1998 Nov 19;41(24):4800-18. [9822550 ]
Handler N, Brunhofer G, Studenik C, Leisser K, Jaeger W, Parth S, Erker T: 'Bridged' stilbene derivatives as selective cyclooxygenase-1 inhibitors. Bioorg Med Chem. 2007 Sep 15;15(18):6109-18. Epub 2007 Jun 20. [17604631 ]
Kakuta H, Zheng X, Oda H, Harada S, Sugimoto Y, Sasaki K, Tai A: Cyclooxygenase-1-selective inhibitors are attractive candidates for analgesics that do not cause gastric damage. design and in vitro/in vivo evaluation of a benzamide-type cyclooxygenase-1 selective inhibitor. J Med Chem. 2008 Apr 24;51(8):2400-11. doi: 10.1021/jm701191z. Epub 2008 Mar 26. [18363350 ]
Khan KM, Ambreen N, Mughal UR, Jalil S, Perveen S, Choudhary MI: 3-Formylchromones: potential antiinflammatory agents. Eur J Med Chem. 2010 Sep;45(9):4058-64. doi: 10.1016/j.ejmech.2010.05.065. Epub 2010 Jun 8. [20576329 ]
Wang H, Nair MG, Strasburg GM, Chang YC, Booren AM, Gray JI, DeWitt DL: Antioxidant and antiinflammatory activities of anthocyanins and their aglycon, cyanidin, from tart cherries. J Nat Prod. 1999 Feb;62(2):294-6. [10075763 ]
Takahashi T, Miyazawa M: N-Caffeoyl serotonin as selective COX-2 inhibitor. Bioorg Med Chem Lett. 2012 Apr 1;22(7):2494-6. doi: 10.1016/j.bmcl.2012.02.002. Epub 2012 Feb 9. [22386242 ]
Wilkerson WW, Copeland RA, Covington M, Trzaskos JM: Antiinflammatory 4,5-diarylpyrroles. 2. Activity as a function of cyclooxygenase-2 inhibition. J Med Chem. 1995 Sep 29;38(20):3895-901. [7562922 ]
Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
Cryer B, Feldman M: Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. Am J Med. 1998 May;104(5):413-21. [9626023 ]

Target Details

2. Prostaglandin G/H synthase 1

General Function:: Prostaglandin-endoperoxide synthase activity
Specific Function:: Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells.
Gene Name:: PTGS1
Uniprot ID:: P23219
Molecular Weight:: 68685.82 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	100 uM	Not Available	BindingDB 22360
IC50	560.1 uM	Not Available	BindingDB 22360
IC50	750.41 uM	Not Available	BindingDB 22360

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Stevenson DD, Szczeklik A: Clinical and pathologic perspectives on aspirin sensitivity and asthma. J Allergy Clin Immunol. 2006 Oct;118(4):773-86; quiz 787-8. Epub 2006 Sep 1. [17030227 ]
Flipo RM: [Are the NSAIDs able to compromising the cardio-preventive efficacy of aspirin?]. Presse Med. 2006 Sep;35(9 Spec No 1):1S53-60. [17078596 ]
Schwartz KA: Aspirin resistance: a review of diagnostic methodology, mechanisms, and clinical utility. Adv Clin Chem. 2006;42:81-110. [17131625 ]
Birnbaum Y, Ye Y, Lin Y, Freeberg SY, Huang MH, Perez-Polo JR, Uretsky BF: Aspirin augments 15-epi-lipoxin A4 production by lipopolysaccharide, but blocks the pioglitazone and atorvastatin induction of 15-epi-lipoxin A4 in the rat heart. Prostaglandins Other Lipid Mediat. 2007 Feb;83(1-2):89-98. Epub 2006 Nov 7. [17259075 ]
Guthikonda S, Lev EI, Patel R, DeLao T, Bergeron AL, Dong JF, Kleiman NS: Reticulated platelets and uninhibited COX-1 and COX-2 decrease the antiplatelet effects of aspirin. J Thromb Haemost. 2007 Mar;5(3):490-6. [17319904 ]
Kakuta H, Zheng X, Oda H, Harada S, Sugimoto Y, Sasaki K, Tai A: Cyclooxygenase-1-selective inhibitors are attractive candidates for analgesics that do not cause gastric damage. design and in vitro/in vivo evaluation of a benzamide-type cyclooxygenase-1 selective inhibitor. J Med Chem. 2008 Apr 24;51(8):2400-11. doi: 10.1021/jm701191z. Epub 2008 Mar 26. [18363350 ]
Takahashi T, Miyazawa M: N-Caffeoyl serotonin as selective COX-2 inhibitor. Bioorg Med Chem Lett. 2012 Apr 1;22(7):2494-6. doi: 10.1016/j.bmcl.2012.02.002. Epub 2012 Feb 9. [22386242 ]
Khan KM, Ambreen N, Mughal UR, Jalil S, Perveen S, Choudhary MI: 3-Formylchromones: potential antiinflammatory agents. Eur J Med Chem. 2010 Sep;45(9):4058-64. doi: 10.1016/j.ejmech.2010.05.065. Epub 2010 Jun 8. [20576329 ]

Target Details

3. 5'-AMP-activated protein kinase catalytic subunit alpha-1

General Function:: Tau-protein kinase activity
Specific Function:: Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1. AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.
Gene Name:: PRKAA1
Uniprot ID:: Q13131
Molecular Weight:: 64008.64 Da

References

Din FV, Valanciute A, Houde VP, Zibrova D, Green KA, Sakamoto K, Alessi DR, Dunlop MG: Aspirin inhibits mTOR signaling, activates AMP-activated protein kinase, and induces autophagy in colorectal cancer cells. Gastroenterology. 2012 Jun;142(7):1504-15.e3. doi: 10.1053/j.gastro.2012.02.050. Epub 2012 Mar 6. [22406476 ]
Hawley SA, Fullerton MD, Ross FA, Schertzer JD, Chevtzoff C, Walker KJ, Peggie MW, Zibrova D, Green KA, Mustard KJ, Kemp BE, Sakamoto K, Steinberg GR, Hardie DG: The ancient drug salicylate directly activates AMP-activated protein kinase. Science. 2012 May 18;336(6083):918-22. doi: 10.1126/science.1215327. Epub 2012 Apr 19. [22517326 ]

Target Details

4. Acidic phospholipase A2 3

General Function:: Phospholipase a2 activity
Specific Function:: PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.
Gene Name:: Not Available
Uniprot ID:: P60045
Molecular Weight:: 13968.385 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 ]

Target Details

5. Basic phospholipase A2 VRV-PL-VIIIa

General Function:: Phospholipase a2 activity
Specific Function:: Snake venom phospholipase A2 (PLA2) that shows weak neurotoxicity and medium anticoagulant effects by binding to factor Xa (F10) and inhibiting the prothrombinase activity (IC(50) is 130 nM) (PubMed:18062812). It also damages vital organs such as lung, liver and kidney, displays edema-inducing activities when injected into the foot pads of mice and induces necrosis of muscle cells when injected into the thigh muscle. Has a low enzymatic activity. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.
Gene Name:: Not Available
Uniprot ID:: P59071
Molecular Weight:: 13610.55 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 ]

Target Details

6. 78 kDa glucose-regulated protein

General Function:: Unfolded protein binding
Specific Function:: Probably plays a role in facilitating the assembly of multimeric protein complexes inside the endoplasmic reticulum. Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10, probably to facilitate the release of DNAJC10 from its substrate.
Gene Name:: HSPA5
Uniprot ID:: P11021
Molecular Weight:: 72332.425 Da

References

Deng WG, Ruan KH, Du M, Saunders MA, Wu KK: Aspirin and salicylate bind to immunoglobulin heavy chain binding protein (BiP) and inhibit its ATPase activity in human fibroblasts. FASEB J. 2001 Nov;15(13):2463-70. [11689471 ]

Target Details

7. Aldo-keto reductase family 1 member C1

General Function:: Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
Specific Function:: Converts progesterone to its inactive form, 20-alpha-dihydroxyprogesterone (20-alpha-OHP). In the liver and intestine, may have a role in the transport of bile. May have a role in monitoring the intrahepatic bile acid concentration. Has a low bile-binding ability. May play a role in myelin formation.
Gene Name:: AKR1C1
Uniprot ID:: Q04828
Molecular Weight:: 36788.02 Da

References

Dhagat U, Carbone V, Chung RP, Matsunaga T, Endo S, Hara A, El-Kabbani O: A salicylic acid-based analogue discovered from virtual screening as a potent inhibitor of human 20alpha-hydroxysteroid dehydrogenase. Med Chem. 2007 Nov;3(6):546-50. [18045204 ]

Target Details

8. Carbonic anhydrase 1

General Function:: Zinc ion binding
Specific Function:: Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
Gene Name:: CA1
Uniprot ID:: P00915
Molecular Weight:: 28870.0 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	7530 uM	Not Available	BindingDB 22360
IC50	2710 uM	Not Available	BindingDB 22360

References

Bayram E, Senturk M, Kufrevioglu OI, Supuran CT: In vitro inhibition of salicylic acid derivatives on human cytosolic carbonic anhydrase isozymes I and II. Bioorg Med Chem. 2008 Oct 15;16(20):9101-5. doi: 10.1016/j.bmc.2008.09.028. Epub 2008 Sep 13. [18819808 ]

Target Details

9. Carbonic anhydrase 2

General Function:: Zinc ion binding
Specific Function:: Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Stimulates the chloride-bicarbonate exchange activity of SLC26A6.
Gene Name:: CA2
Uniprot ID:: P00918
Molecular Weight:: 29245.895 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	3660 uM	Not Available	BindingDB 22360
IC50	1160 uM	Not Available	BindingDB 22360

References

Bayram E, Senturk M, Kufrevioglu OI, Supuran CT: In vitro inhibition of salicylic acid derivatives on human cytosolic carbonic anhydrase isozymes I and II. Bioorg Med Chem. 2008 Oct 15;16(20):9101-5. doi: 10.1016/j.bmc.2008.09.028. Epub 2008 Sep 13. [18819808 ]

Target Details

10. Cellular tumor antigen p53

General Function:: Not Available
Specific Function:: Not Available
Gene Name:: TP53
Uniprot ID:: P04637
Molecular Weight:: 43652.79 Da

References

Alfonso LF, Srivenugopal KS, Bhat GJ: Does aspirin acetylate multiple cellular proteins? (Review). Mol Med Rep. 2009 Jul-Aug;2(4):533-7. doi: 10.3892/mmr_00000132. [21475861 ]

Target Details

11. Endothelin-1 receptor

General Function:: Phosphatidylinositol phospholipase c activity
Specific Function:: Receptor for endothelin-1. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of binding affinities for ET-A is: ET1 > ET2 >> ET3.
Gene Name:: EDNRA
Uniprot ID:: P25101
Molecular Weight:: 48721.76 Da

References

Talbodec A, Berkane N, Blandin V, Breittmayer JP, Ferrari E, Frelin C, Vigne P: Aspirin and sodium salicylate inhibit endothelin ETA receptors by an allosteric type of mechanism. Mol Pharmacol. 2000 Apr;57(4):797-804. [10727528 ]

Target Details

12. Gamma-glutamyltranspeptidase 1

General Function:: Glutathione hydrolase activity
Specific Function:: Cleaves the gamma-glutamyl bond of extracellular glutathione (gamma-Glu-Cys-Gly), glutathione conjugates, and other gamma-glutamyl compounds. The metabolism of glutathione releases free glutamate and the dipeptide, cysteinyl-glycine, which is hydrolyzed to cysteine and glycine by dipeptidases. In the presence of high concentrations of dipeptides and some amino acids, can also catalyze a transpeptidation reaction, transferring the gamma-glutamyl moiety to an acceptor amino acid to form a new gamma-glutamyl compound. Initiates extracellular glutathione (GSH) breakdown, provides cells with a local cysteine supply and contributes to maintain intracellular GSH level. It is part of the cell antioxidant defense mechanism. Isoform 3 seems to be inactive.
Gene Name:: GGT1
Uniprot ID:: P19440
Molecular Weight:: 61409.67 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	36 uM	Not Available	BindingDB 22360

References

Sadanandam YS, Shetty MM, Rao AB, Rambabu Y: 10H-Phenothiazines: a new class of enzyme inhibitors for inflammatory diseases. Eur J Med Chem. 2009 Jan;44(1):197-202. doi: 10.1016/j.ejmech.2008.02.028. Epub 2008 Mar 7. [18400337 ]

Target Details

13. Inhibitor of nuclear factor kappa-B kinase subunit beta

General Function:: Scaffold protein binding
Specific Function:: Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation.
Gene Name:: IKBKB
Uniprot ID:: O14920
Molecular Weight:: 86563.245 Da

References

Yin MJ, Yamamoto Y, Gaynor RB: The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Nature. 1998 Nov 5;396(6706):77-80. [9817203 ]

Target Details

14. Integrin alpha-IIb

General Function:: Metal ion binding
Specific Function:: Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial cell surface.
Gene Name:: ITGA2B
Uniprot ID:: P08514
Molecular Weight:: 113375.96 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	5 uM	Not Available	BindingDB 22360
IC50	>100 uM	Not Available	BindingDB 22360

References

Sanfilippo PJ, Urbanski MJ, Beers KN, Eckardt A, Falotico R, Ginsberg MH, Offord S, Press JB, Tighe J, Tomko K, et al.: Novel thiazole-based heterocycles as selective inhibitors of fibrinogen-mediated platelet aggregation. J Med Chem. 1995 Jan 6;38(1):34-41. [7837237 ]

Target Details

15. NF-kappa-B inhibitor alpha

General Function:: Ubiquitin protein ligase binding
Specific Function:: Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL dimers in the cytoplasm through masking of their nuclear localization signals. On cellular stimulation by immune and proinflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription.
Gene Name:: NFKBIA
Uniprot ID:: P25963
Molecular Weight:: 35608.65 Da

References

Stevenson MA, Zhao MJ, Asea A, Coleman CN, Calderwood SK: Salicylic acid and aspirin inhibit the activity of RSK2 kinase and repress RSK2-dependent transcription of cyclic AMP response element binding protein- and NF-kappa B-responsive genes. J Immunol. 1999 Nov 15;163(10):5608-16. [10553090 ]

Target Details

16. Nuclear factor NF-kappa-B p100 subunit

General Function:: Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific Function:: NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. In a non-canonical activation pathway, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65. In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer.
Gene Name:: NFKB2
Uniprot ID:: Q00653
Molecular Weight:: 96748.355 Da

References

Kopp E, Ghosh S: Inhibition of NF-kappa B by sodium salicylate and aspirin. Science. 1994 Aug 12;265(5174):956-9. [8052854 ]

Target Details

17. Ribosomal protein S6 kinase alpha-3

General Function:: Ribosomal protein s6 kinase activity
Specific Function:: Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP. Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation. Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway. Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function. Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression. In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3. Phosphorylates DAPK1.
Gene Name:: RPS6KA3
Uniprot ID:: P51812
Molecular Weight:: 83735.325 Da

References

Stevenson MA, Zhao MJ, Asea A, Coleman CN, Calderwood SK: Salicylic acid and aspirin inhibit the activity of RSK2 kinase and repress RSK2-dependent transcription of cyclic AMP response element binding protein- and NF-kappa B-responsive genes. J Immunol. 1999 Nov 15;163(10):5608-16. [10553090 ]

Target Details

18. Thyroid hormone receptor alpha

General Function:: Zinc ion binding
Specific Function:: Isoform Alpha-1: Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.Isoform Alpha-2: Does not bind thyroid hormone and functions as a weak dominant negative inhibitor of thyroid hormone action.
Gene Name:: THRA
Uniprot ID:: P10827
Molecular Weight:: 54815.055 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	0.96 uM	ATG_THRa1_TRANS	Attagene

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 ]

Aspirin (T3D2936)

Structure for T3D2936: Aspirin

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