T3DB: Adenosine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (11)XML

Targets (11)

Record Information

Version

2.0

Creation Date

2014-08-29 06:11:54 UTC

Update Date

2018-03-21 17:46:14 UTC

Accession Number

T3D4275

Identification

Common Name

Adenosine

Class

Small Molecule

Description

Adenosine is a nucleoside that is composed of adenine and D-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. For instance, adenosine plays an important role in energy transfer as adenosine triphosphate (ATP) and adenosine diphosphate (ADP). It also plays a role in signal transduction as cyclic adenosine monophosphate (cAMP). Adenosine itself is both a neurotransmitter and potent vasodilator. When administered intravenously adenosine causes transient heart block in the AV node. Due to the effects of adenosine on AV node-dependent supraventricular tachycardia, adenosine is considered a class V antiarrhythmic agent. Overdoses of adenosine intake (as a drug) can lead to several side effects including chest pain, feeling faint, shortness of breath, and tingling of the senses. Serious side effects include a worsening dysrhythmia and low blood pressure. When present in sufficiently high levels, adenosine can act as an immunotoxin and a metabotoxin. An immunotoxin disrupts, limits the function, or destroys immune cells. A metabotoxin is an endogenous metabolite that causes adverse health effects at chronically high levels. Chronically high levels of adenosine are associated with adenosine deaminase deficiency. Adenosine is a precursor to deoxyadenosine, which is a precursor to dATP. A buildup of dATP in cells inhibits ribonucleotide reductase and prevents DNA synthesis, so cells are unable to divide. Since developing T cells and B cells are some of the most mitotically active cells, they are unable to divide and propagate to respond to immune challenges. High levels of deoxyadenosine also lead to an increase in S-adenosylhomocysteine, which is toxic to immature lymphocytes.

Compound Type

Amine
Analgesic
Animal Toxin
Anti-Arrhythmia Agent
Cardiovascular Agent
Drug
Ether
Food Toxin
Metabolite
Natural Compound
Organic Compound
Vasodilator Agent

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
(2R,3R,4S,5R)-2-(6-Aminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
1-(6-Amino-9H-purin-9-yl)-1-deoxy-beta-D-Ribofuranose
1-(6-Amino-9H-purin-9-yl)-1-deoxy-beta-delta-Ribofuranose
6-Amino-9-beta-D-ribofuranosyl-9H-purine
6-Amino-9beta-D-ribofuranosyl-9H-purine
6-Amino-9beta-delta-ribofuranosyl-9H-purine
9-beta-D-Arabinofuranosyladenine
9-beta-D-Ribofuranosidoadenine
9-beta-D-Ribofuranosyl-9H-purin-6-amine
9-beta-D-Ribofuranosyladenine
9-beta-delta-Arabinofuranosyladenine
9-beta-delta-Ribofuranosidoadenine
9-beta-delta-Ribofuranosyl-9H-purin-6-amine
9-beta-delta-Ribofuranosyladenine
9beta-D-ribofuranosyl-9H-Purin-6-amine
9beta-D-Ribofuranosyladenine
9beta-delta-ribofuranosyl-9H-Purin-6-amine
9beta-delta-Ribofuranosyladenine
Ade-rib
Adenin riboside
Adenine deoxyribonucleoside
Adenine nucleoside
Adenine riboside
Adenine-9beta-D-Ribofuranoside
Adenine-9beta-delta-Ribofuranoside
Adenocard
Adenocor
Adenoject
Adenoscan
Adenosin
Adenosina
Adénosine
Adenosinum
Adenoz
Adenozer
Adenyldeoxyriboside
Adesin
Ado
Adrekar
Atépadène
b-D-Adenosine
beta-Adenosine
beta-D-Adenosine
beta-delta-Adenosine
Boniton
Cardimax
Cardiovert
Desoxyadenosine
Krenosin
Myocol
Nucleocardyl
Osiden
Pisdeno
Sandesin
Tricor

Chemical Formula

C₁₀H₁₃N₅O₄

Average Molecular Mass

267.241 g/mol

Monoisotopic Mass

267.097 g/mol

CAS Registry Number

58-61-7

IUPAC Name

(2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol

Traditional Name

adenosine

SMILES

[H][C@]1(CO)O[C@@]([H])(N2C=NC3=C(N)N=CN=C23)[C@]([H])(O)[C@]1([H])O

InChI Identifier

InChI=1S/C10H13N5O4/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(18)6(17)4(1-16)19-10/h2-4,6-7,10,16-18H,1H2,(H2,11,12,13)/t4-,6-,7-,10-/m1/s1

InChI Key

InChIKey=OIRDTQYFTABQOQ-KQYNXXCUSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as purine nucleosides. Purine nucleosides are compounds comprising a purine base attached to a ribosyl or deoxyribosyl moiety.

Kingdom

Organic compounds

Super Class

Nucleosides, nucleotides, and analogues

Class

Purine nucleosides

Sub Class

Not Available

Direct Parent

Purine nucleosides

Alternative Parents

Substituents

Purine nucleoside
Glycosyl compound
N-glycosyl compound
6-aminopurine
Pentose monosaccharide
Imidazopyrimidine
Purine
Aminopyrimidine
Monosaccharide
N-substituted imidazole
Pyrimidine
Imidolactam
Tetrahydrofuran
Azole
Imidazole
Heteroaromatic compound
Secondary alcohol
Organoheterocyclic compound
Azacycle
Oxacycle
Organic oxygen compound
Organic nitrogen compound
Alcohol
Organonitrogen compound
Hydrocarbon derivative
Organopnictogen compound
Organooxygen compound
Amine
Primary alcohol
Primary amine
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

adenosines (CHEBI:16335 )
Ribonucleosides (C00212 )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Extracellular
Lysosome
Membrane
Mitochondria

Biofluid Locations

Not Available

Tissue Locations

All Tissues

Pathways

Name	SMPDB Link	KEGG Link
Purine Metabolism	SMP00050	map00230
Adenosine Deaminase Deficiency	SMP00144	Not Available

Applications

Biological Roles

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	235.5°C
Boiling Point	Not Available
Solubility	8230 mg/L
LogP	-1.05

Predicted Properties

Property	Value	Source
Water Solubility	14 g/L	ALOGPS
logP	-1.2	ALOGPS
logP	-2.1	ChemAxon
logS	-1.3	ALOGPS
pKa (Strongest Acidic)	12.45	ChemAxon
pKa (Strongest Basic)	3.92	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	8	ChemAxon
Hydrogen Donor Count	4	ChemAxon
Polar Surface Area	139.54 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	63.2 m³·mol⁻¹	ChemAxon
Polarizability	25.28 Å³	ChemAxon
Number of Rings	3	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) (4 TMS)	splash10-0f7w-1890000000-5c70a5423faa5e8eceaf	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (4 TMS)	splash10-001v-0691000000-8f88854b7d5adec5c558	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)	splash10-001s-0790000000-cc3bcd977e11efd4ea25	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (4 TMS)	splash10-00di-9460000000-3ae19bfaa5d2df72f9b1	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (3 TMS)	splash10-0gc0-0590000000-05874cecded3009c1f4d	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (4 TMS)	splash10-0fsv-1792000000-b37fd6826f28aaf9e825	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0f7w-1890000000-5c70a5423faa5e8eceaf	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-001v-0691000000-8f88854b7d5adec5c558	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-001s-0790000000-cc3bcd977e11efd4ea25	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-00di-9460000000-3ae19bfaa5d2df72f9b1	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-0gc0-0590000000-05874cecded3009c1f4d	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-0fsv-1792000000-b37fd6826f28aaf9e825	2017-09-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0a4v-9560000000-986f3b1dfa5d898ed7a2	2016-09-22	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positive	splash10-01c4-6912500000-ae103f43432726c1ad22	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
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_4) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_4) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_5) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_6) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-014r-0890000000-588861a9494ab4680698	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-000i-1900000000-dd7cbed8e76c6e783831	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-000i-2900000000-c6644520b5943b59403d	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-014i-0090000000-3d4fd8ea211eaed10531	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-000i-0900000000-cb58ec56a5faa09c9a02	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-000i-0900000000-9559aa07ec13a688fb16	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positive	splash10-000i-0900000000-f7c1371d8e1058df3a32	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negative	splash10-001i-0940000000-da71247788bf1ba222e2	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negative	splash10-001i-0920000000-f2e8ec028abdd674b5e3	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negative	splash10-001i-0910000000-815ed65588c07415cd65	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negative	splash10-001i-1910000000-2780e737da8848411c4f	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negative	splash10-053r-1900000000-c6c1128990661334c15b	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positive	splash10-014i-0090000000-106e7131507fadd4befb	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positive	splash10-000i-0910000000-1c53823486cd2c23f90e	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positive	splash10-000i-0900000000-f0313435db4847490fd6	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positive	splash10-000i-1900000000-dcd4c2972882dcd7535a	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positive	splash10-000i-2900000000-5ee474864189cef6df64	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positive	splash10-000i-0900000000-17edf36faf6eb5750912	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positive	splash10-000i-0900000000-0591143763a0bad31c23	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positive	splash10-014i-0290000000-f1d71a97ce39145c8e31	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) 30V, Positive	splash10-00kr-0950000000-9bbdbb14aed287ad5ac8	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negative	splash10-001i-0910000000-35f90965f1f3c2b3236b	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positive	splash10-000i-0900000000-f360cca994696d7ae735	2012-08-31	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-000i-0940000000-42bee9785f9b55b32eea	2016-09-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-000i-0900000000-c8cda6a661ace060572c	2016-09-12	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, H₂O, experimental)	Not Available	2012-12-04	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 125 MHz, H₂O, experimental)	Not Available	2012-12-04	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, H₂O, experimental)	Not Available	2021-10-10	View Spectrum
2D NMR	[¹H, ¹H]-TOCSY. Unexported temporarily by An Chi on Oct 15, 2021 until json or nmrML file is generated. 2D NMR Spectrum (experimental)	Not Available	2012-12-04	View Spectrum
2D NMR	[¹H, ¹³C]-HSQC NMR Spectrum (2D, 400 MHz, H₂O, experimental)	Not Available	2012-12-04	View Spectrum

Toxicity Profile

Route of Exposure

Not Available

Mechanism of Toxicity

Adenosine slows conduction time through the AV node and can interrupt the reentry pathways through the AV node, resulting in the restoration of normal sinus rhythm in patients with paroxysmal supraventricular tachycardia (PSVT), including PSVT associated with Wolff-Parkinson-White Syndrome. This effect may be mediated through the drug's activation of cell-surface A₁ and A₂ adenosine receptors. Adenosine also inhibits the slow inward calcium current and activation of adenylate cyclase in smooth muscle cells, thereby causing relaxation of vascular smooth muscle. By increasing blood flow in normal coronary arteries with little or no increase in stenotic arteries (with little to no increase in stenotic arteries), adenosine produces a relative difference in thallous (thallium) chloride TI 201 uptake in myocardium supplied by normal verus stenotic coronary arteries.

Metabolism

Intracellular adenosine is rapidly metabolized either via phosphorylation to adenosine monophosphate by adenosine kinase, or via deamination to inosine by adenosine deaminase in the cytosol. Half Life: Less than 10 secs

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

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

Uses/Sources

Used as an initial treatment for the termination of paroxysmal supraventricular tachycardia (PVST), including that associated with accessory bypass tracts, and is a drug of choice for terminating stable, narrow-complex supraventricular tachycardias (SVT). Also used as an adjunct to thallous chloride TI 201 myocardial perfusion scintigraphy (thallium stress test) in patients who are unable to exercise adequately, as well as an adjunct to vagal maneuvers and clinical assessment to establish a specific diagnosis of undefined, stable, narrow-complex SVT.

Minimum Risk Level

Not Available

Health Effects

Chronically high levels of adeonsine are associated with Adenosine Deaminase Deficiency.

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

16335

BioCyc ID

ADENOSINE

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

ADN

ACToR ID

Not Available

Wikipedia Link

Adenosine

References

Synthesis Reference

Giorgio Stramentinoli, Federico Gennari, “Process for preparing adenosine derivatives of anti-inflammatory and analgesic activity.” U.S. Patent US4373097, issued October, 1965.

MSDS

Link

General References

Skalhegg BS, Funderud A, Henanger HH, Hafte TT, Larsen AC, Kvissel AK, Eikvar S, Orstavik S: Protein kinase A (PKA)--a potential target for therapeutic intervention of dysfunctional immune cells. Curr Drug Targets. 2005 Sep;6(6):655-64. [16178799 ]
Nakayama Y, Kinoshita A, Tomita M: Dynamic simulation of red blood cell metabolism and its application to the analysis of a pathological condition. Theor Biol Med Model. 2005 May 9;2:18. [15882454 ]
Lee SH, Jung BH, Kim SY, Chung BC: A rapid and sensitive method for quantitation of nucleosides in human urine using liquid chromatography/mass spectrometry with direct urine injection. Rapid Commun Mass Spectrom. 2004;18(9):973-7. [15116424 ]
Maytin M, Colucci WS: Cardioprotection: a new paradigm in the management of acute heart failure syndromes. Am J Cardiol. 2005 Sep 19;96(6A):26G-31G. [16181820 ]
Dodge-Kafka KL, Soughayer J, Pare GC, Carlisle Michel JJ, Langeberg LK, Kapiloff MS, Scott JD: The protein kinase A anchoring protein mAKAP coordinates two integrated cAMP effector pathways. Nature. 2005 Sep 22;437(7058):574-8. [16177794 ]
Gheorghiade M, Teerlink JR, Mebazaa A: Pharmacology of new agents for acute heart failure syndromes. Am J Cardiol. 2005 Sep 19;96(6A):68G-73G. [16181825 ]
Jansen RW, Kruijt JK, van Berkel TJ, Meijer DK: Coupling of the antiviral drug ara-AMP to lactosaminated albumin leads to specific uptake in rat and human hepatocytes. Hepatology. 1993 Jul;18(1):146-52. [7686877 ]
Ballantyne PJ: Social context and outcomes for the ageing breast cancer patient: considerations for clinical practitioners. J Clin Nurs. 2004 Mar;13(3a):11-21. [15028034 ]
Yamamoto T, Moriwaki Y, Takahashi S, Fujita T, Tsutsumi Z, Yamakita J, Shimizu K, Shiota M, Ohta S, Higashino K: Determination of adenosine and deoxyadenosine in urine by high-performance liquid chromatography with column switching. J Chromatogr B Biomed Sci Appl. 1998 Nov 20;719(1-2):55-61. [9869364 ]
Eells JT, Spector R: Purine and pyrimidine base and nucleoside concentrations in human cerebrospinal fluid and plasma. Neurochem Res. 1983 Nov;8(11):1451-7. [6656991 ]
Koeris M, Funke L, Shrestha J, Rich A, Maas S: Modulation of ADAR1 editing activity by Z-RNA in vitro. Nucleic Acids Res. 2005 Sep 21;33(16):5362-70. Print 2005. [16177183 ]
Vidotto C, Fousert D, Akkermann M, Griesmacher A, Muller MM: Purine and pyrimidine metabolites in children's urine. Clin Chim Acta. 2003 Sep;335(1-2):27-32. [12927681 ]
Dunne VG, Bhattachayya S, Besser M, Rae C, Griffin JL: Metabolites from cerebrospinal fluid in aneurysmal subarachnoid haemorrhage correlate with vasospasm and clinical outcome: a pattern-recognition 1H NMR study. NMR Biomed. 2005 Feb;18(1):24-33. [15455468 ]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Adenosine receptor A2a

General Function:: Identical protein binding
Specific Function:: Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Gene Name:: ADORA2A
Uniprot ID:: P29274
Molecular Weight:: 44706.925 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.02 uM	Not Available	BindingDB 14487

References

Trincavelli ML, Daniele S, Martini C: Adenosine receptors: what we know and what we are learning. Curr Top Med Chem. 2010;10(9):860-77. [20370662 ]
Schenone S, Brullo C, Musumeci F, Bruno O, Botta M: A1 receptors ligands: past, present and future trends. Curr Top Med Chem. 2010;10(9):878-901. [20370661 ]
Ezeamuzie CI, Khan I: The role of adenosine A(2) receptors in the regulation of TNF-alpha production and PGE(2) release in mouse peritoneal macrophages. Int Immunopharmacol. 2007 Apr;7(4):483-90. Epub 2006 Dec 29. [17321471 ]
Kreckler LM, Wan TC, Ge ZD, Auchampach JA: Adenosine inhibits tumor necrosis factor-alpha release from mouse peritoneal macrophages via A2A and A2B but not the A3 adenosine receptor. J Pharmacol Exp Ther. 2006 Apr;317(1):172-80. Epub 2005 Dec 9. [16339914 ]
Kreckler LM, Gizewski E, Wan TC, Auchampach JA: Adenosine suppresses lipopolysaccharide-induced tumor necrosis factor-alpha production by murine macrophages through a protein kinase A- and exchange protein activated by cAMP-independent signaling pathway. J Pharmacol Exp Ther. 2009 Dec;331(3):1051-61. doi: 10.1124/jpet.109.157651. Epub 2009 Sep 11. [19749080 ]
Buenestado A, Grassin Delyle S, Arnould I, Besnard F, Naline E, Blouquit-Laye S, Chapelier A, Bellamy JF, Devillier P: The role of adenosine receptors in regulating production of tumour necrosis factor-alpha and chemokines by human lung macrophages. Br J Pharmacol. 2010 Mar;159(6):1304-11. doi: 10.1111/j.1476-5381.2009.00614.x. Epub 2010 Feb 5. [20136829 ]
Funakoshi H, Zacharia LC, Tang Z, Zhang J, Lee LL, Good JC, Herrmann DE, Higuchi Y, Koch WJ, Jackson EK, Chan TO, Feldman AM: A1 adenosine receptor upregulation accompanies decreasing myocardial adenosine levels in mice with left ventricular dysfunction. Circulation. 2007 May 1;115(17):2307-15. Epub 2007 Apr 16. [17438146 ]
Haschemi A, Wagner O, Marculescu R, Wegiel B, Robson SC, Gagliani N, Gallo D, Chen JF, Bach FH, Otterbein LE: Cross-regulation of carbon monoxide and the adenosine A2a receptor in macrophages. J Immunol. 2007 May 1;178(9):5921-9. [17442976 ]
Deflorian F, Kumar TS, Phan K, Gao ZG, Xu F, Wu H, Katritch V, Stevens RC, Jacobson KA: Evaluation of molecular modeling of agonist binding in light of the crystallographic structure of an agonist-bound A(2)A adenosine receptor. J Med Chem. 2012 Jan 12;55(1):538-52. doi: 10.1021/jm201461q. Epub 2011 Dec 12. [22104008 ]
Lambertucci C, Cristalli G, Dal Ben D, Kachare DD, Bolcato C, Klotz KN, Spalluto G, Volpini R: New 2,6,9-trisubstituted adenines as adenosine receptor antagonists: a preliminary SAR profile. Purinergic Signal. 2007 Sep;3(4):339-46. doi: 10.1007/s11302-007-9068-9. Epub 2007 Sep 19. [18404447 ]

Target Details

2. Adenosine receptor A3

General Function:: G-protein coupled adenosine receptor activity
Specific Function:: Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. Possible role in reproduction.
Gene Name:: ADORA3
Uniprot ID:: P0DMS8
Molecular Weight:: 36184.175 Da

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Trincavelli ML, Daniele S, Martini C: Adenosine receptors: what we know and what we are learning. Curr Top Med Chem. 2010;10(9):860-77. [20370662 ]
Schenone S, Brullo C, Musumeci F, Bruno O, Botta M: A1 receptors ligands: past, present and future trends. Curr Top Med Chem. 2010;10(9):878-901. [20370661 ]
Ezeamuzie CI, Khan I: The role of adenosine A(2) receptors in the regulation of TNF-alpha production and PGE(2) release in mouse peritoneal macrophages. Int Immunopharmacol. 2007 Apr;7(4):483-90. Epub 2006 Dec 29. [17321471 ]
Kreckler LM, Wan TC, Ge ZD, Auchampach JA: Adenosine inhibits tumor necrosis factor-alpha release from mouse peritoneal macrophages via A2A and A2B but not the A3 adenosine receptor. J Pharmacol Exp Ther. 2006 Apr;317(1):172-80. Epub 2005 Dec 9. [16339914 ]
Buenestado A, Grassin Delyle S, Arnould I, Besnard F, Naline E, Blouquit-Laye S, Chapelier A, Bellamy JF, Devillier P: The role of adenosine receptors in regulating production of tumour necrosis factor-alpha and chemokines by human lung macrophages. Br J Pharmacol. 2010 Mar;159(6):1304-11. doi: 10.1111/j.1476-5381.2009.00614.x. Epub 2010 Feb 5. [20136829 ]
Funakoshi H, Zacharia LC, Tang Z, Zhang J, Lee LL, Good JC, Herrmann DE, Higuchi Y, Koch WJ, Jackson EK, Chan TO, Feldman AM: A1 adenosine receptor upregulation accompanies decreasing myocardial adenosine levels in mice with left ventricular dysfunction. Circulation. 2007 May 1;115(17):2307-15. Epub 2007 Apr 16. [17438146 ]
Haschemi A, Wagner O, Marculescu R, Wegiel B, Robson SC, Gagliani N, Gallo D, Chen JF, Bach FH, Otterbein LE: Cross-regulation of carbon monoxide and the adenosine A2a receptor in macrophages. J Immunol. 2007 May 1;178(9):5921-9. [17442976 ]
Lambertucci C, Cristalli G, Dal Ben D, Kachare DD, Bolcato C, Klotz KN, Spalluto G, Volpini R: New 2,6,9-trisubstituted adenines as adenosine receptor antagonists: a preliminary SAR profile. Purinergic Signal. 2007 Sep;3(4):339-46. doi: 10.1007/s11302-007-9068-9. Epub 2007 Sep 19. [18404447 ]

Target Details

3. Adenosine receptor A1

General Function:: Purine nucleoside binding
Specific Function:: Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name:: ADORA1
Uniprot ID:: P30542
Molecular Weight:: 36511.325 Da

References

Trincavelli ML, Daniele S, Martini C: Adenosine receptors: what we know and what we are learning. Curr Top Med Chem. 2010;10(9):860-77. [20370662 ]
Schenone S, Brullo C, Musumeci F, Bruno O, Botta M: A1 receptors ligands: past, present and future trends. Curr Top Med Chem. 2010;10(9):878-901. [20370661 ]
Ezeamuzie CI, Khan I: The role of adenosine A(2) receptors in the regulation of TNF-alpha production and PGE(2) release in mouse peritoneal macrophages. Int Immunopharmacol. 2007 Apr;7(4):483-90. Epub 2006 Dec 29. [17321471 ]
Buenestado A, Grassin Delyle S, Arnould I, Besnard F, Naline E, Blouquit-Laye S, Chapelier A, Bellamy JF, Devillier P: The role of adenosine receptors in regulating production of tumour necrosis factor-alpha and chemokines by human lung macrophages. Br J Pharmacol. 2010 Mar;159(6):1304-11. doi: 10.1111/j.1476-5381.2009.00614.x. Epub 2010 Feb 5. [20136829 ]
Funakoshi H, Zacharia LC, Tang Z, Zhang J, Lee LL, Good JC, Herrmann DE, Higuchi Y, Koch WJ, Jackson EK, Chan TO, Feldman AM: A1 adenosine receptor upregulation accompanies decreasing myocardial adenosine levels in mice with left ventricular dysfunction. Circulation. 2007 May 1;115(17):2307-15. Epub 2007 Apr 16. [17438146 ]
Haschemi A, Wagner O, Marculescu R, Wegiel B, Robson SC, Gagliani N, Gallo D, Chen JF, Bach FH, Otterbein LE: Cross-regulation of carbon monoxide and the adenosine A2a receptor in macrophages. J Immunol. 2007 May 1;178(9):5921-9. [17442976 ]
Lambertucci C, Cristalli G, Dal Ben D, Kachare DD, Bolcato C, Klotz KN, Spalluto G, Volpini R: New 2,6,9-trisubstituted adenines as adenosine receptor antagonists: a preliminary SAR profile. Purinergic Signal. 2007 Sep;3(4):339-46. doi: 10.1007/s11302-007-9068-9. Epub 2007 Sep 19. [18404447 ]

Target Details

4. Adenosine receptor A2b

General Function:: G-protein coupled adenosine receptor activity
Specific Function:: Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Gene Name:: ADORA2B
Uniprot ID:: P29275
Molecular Weight:: 36332.655 Da

References

Trincavelli ML, Daniele S, Martini C: Adenosine receptors: what we know and what we are learning. Curr Top Med Chem. 2010;10(9):860-77. [20370662 ]
Schenone S, Brullo C, Musumeci F, Bruno O, Botta M: A1 receptors ligands: past, present and future trends. Curr Top Med Chem. 2010;10(9):878-901. [20370661 ]
Ezeamuzie CI, Khan I: The role of adenosine A(2) receptors in the regulation of TNF-alpha production and PGE(2) release in mouse peritoneal macrophages. Int Immunopharmacol. 2007 Apr;7(4):483-90. Epub 2006 Dec 29. [17321471 ]
Kreckler LM, Wan TC, Ge ZD, Auchampach JA: Adenosine inhibits tumor necrosis factor-alpha release from mouse peritoneal macrophages via A2A and A2B but not the A3 adenosine receptor. J Pharmacol Exp Ther. 2006 Apr;317(1):172-80. Epub 2005 Dec 9. [16339914 ]
Buenestado A, Grassin Delyle S, Arnould I, Besnard F, Naline E, Blouquit-Laye S, Chapelier A, Bellamy JF, Devillier P: The role of adenosine receptors in regulating production of tumour necrosis factor-alpha and chemokines by human lung macrophages. Br J Pharmacol. 2010 Mar;159(6):1304-11. doi: 10.1111/j.1476-5381.2009.00614.x. Epub 2010 Feb 5. [20136829 ]
Funakoshi H, Zacharia LC, Tang Z, Zhang J, Lee LL, Good JC, Herrmann DE, Higuchi Y, Koch WJ, Jackson EK, Chan TO, Feldman AM: A1 adenosine receptor upregulation accompanies decreasing myocardial adenosine levels in mice with left ventricular dysfunction. Circulation. 2007 May 1;115(17):2307-15. Epub 2007 Apr 16. [17438146 ]
Haschemi A, Wagner O, Marculescu R, Wegiel B, Robson SC, Gagliani N, Gallo D, Chen JF, Bach FH, Otterbein LE: Cross-regulation of carbon monoxide and the adenosine A2a receptor in macrophages. J Immunol. 2007 May 1;178(9):5921-9. [17442976 ]

Target Details

5. Glyceraldehyde-3-phosphate dehydrogenase

General Function:: Peptidyl-cysteine s-nitrosylase activity
Specific Function:: Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC. Modulates the organization and assembly of the cytoskeleton. Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation.
Gene Name:: GAPDH
Uniprot ID:: P04406
Molecular Weight:: 36053.0 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	2500 uM	Not Available	BindingDB 14487
IC50	35 uM	Not Available	BindingDB 14487
IC50	50 uM	Not Available	BindingDB 14487
IC50	100 uM	Not Available	BindingDB 14487
IC50	35000 uM	Not Available	BindingDB 14487

References

Verlinde CL, Callens M, Van Calenbergh S, Van Aerschot A, Herdewijn P, Hannaert V, Michels PA, Opperdoes FR, Hol WG: Selective inhibition of trypanosomal glyceraldehyde-3-phosphate dehydrogenase by protein structure-based design: toward new drugs for the treatment of sleeping sickness. J Med Chem. 1994 Oct 14;37(21):3605-13. [7932587 ]
Van Calenbergh S, Verlinde CL, Soenens J, De Bruyn A, Callens M, Blaton NM, Peeters OM, Rozenski J, Hol WG, Herdewijn P: Synthesis and structure-activity relationships of analogs of 2'-deoxy-2'-(3-methoxybenzamido)adenosine, a selective inhibitor of trypanosomal glycosomal glyceraldehyde-3-phosphate dehydrogenase. J Med Chem. 1995 Sep 15;38(19):3838-49. [7562915 ]
Aronov AM, Gelb MH: Synthesis and structure-activity relationships of adenosine analogs as inhibitors of trypanosomal glyceraldehyde-3-phosphate dehydrogenase. Modifications at positions 5' and 8. Bioorg Med Chem Lett. 1998 Dec 15;8(24):3505-10. [9934461 ]

Target Details

6. Adenosine deaminase

General Function:: Zinc ion binding
Specific Function:: Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine. Plays an important role in purine metabolism and in adenosine homeostasis. Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events. Acts as a positive regulator of T-cell coactivation, by binding DPP4. Its interaction with DPP4 regulates lymphocyte-epithelial cell adhesion.
Gene Name:: ADA
Uniprot ID:: P00813
Molecular Weight:: 40764.13 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	2180 uM	Not Available	BindingDB 14487

References

Bussolari JC, Ramesh K, Stoeckler JD, Chen SF, Panzica RP: Synthesis and biological evaluation of N4-substituted imidazo- and v-triazolo[4,5-d]pyridazine nucleosides. J Med Chem. 1993 Dec 10;36(25):4113-20. [8258836 ]

Target Details

7. Epidermal growth factor receptor

General Function:: Ubiquitin protein ligase binding
Specific Function:: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin.Isoform 2 may act as an antagonist of EGF action.
Gene Name:: EGFR
Uniprot ID:: P00533
Molecular Weight:: 134276.185 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	195 uM	Not Available	BindingDB 14487

References

Singh J, Dobrusin EM, Fry DW, Haske T, Whitty A, McNamara DJ: Structure-based design of a potent, selective, and irreversible inhibitor of the catalytic domain of the erbB receptor subfamily of protein tyrosine kinases. J Med Chem. 1997 Mar 28;40(7):1130-5. [9089334 ]

8. Heat shock 70 kDa protein 1A/1B (Protein Group)

General Function:: Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The co-chaperones have been shown to not only regulate different steps of the ATPase cycle, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The co-chaperones are of three types: J-domain co-chaperones such as HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24012426, PubMed:26865365, PubMed:24318877). Maintains protein homeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. Its acetylation/deacetylation state determines whether it functions in protein refolding or protein degradation by controlling the competitive binding of co-chaperones HOPX and STUB1. During the early stress response, the acetylated form binds to HOPX which assists in chaperone-mediated protein refolding, thereafter, it is deacetylated and binds to ubiquitin ligase STUB1 that promotes ubiquitin-mediated protein degradation (PubMed:27708256). Regulates centrosome integrity during mitosis, and is required for the maintenance of a functional mitotic centrosome that supports the assembly of a bipolar mitotic spindle (PubMed:27137183). Enhances STUB1-mediated SMAD3 ubiquitination and degradation and facilitates STUB1-mediated inhibition of TGF-beta signaling (PubMed:24613385). Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation (PubMed:23973223). Negatively regulates heat shock-induced HSF1 transcriptional activity during the attenuation and recovery phase period of the heat shock response (PubMed:9499401).
Specific Function:: Atp binding
Included Proteins:: P0DMV8 , P0DMV9

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	560 uM	Not Available	BindingDB 14487

References

Williamson DS, Borgognoni J, Clay A, Daniels Z, Dokurno P, Drysdale MJ, Foloppe N, Francis GL, Graham CJ, Howes R, Macias AT, Murray JB, Parsons R, Shaw T, Surgenor AE, Terry L, Wang Y, Wood M, Massey AJ: Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design. J Med Chem. 2009 Mar 26;52(6):1510-3. doi: 10.1021/jm801627a. [19256508 ]

Target Details

9. Inosine-5'-monophosphate dehydrogenase 1

General Function:: Rna binding
Specific Function:: Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors.
Gene Name:: IMPDH1
Uniprot ID:: P20839
Molecular Weight:: 55405.365 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	>100 uM	Not Available	BindingDB 14487

References

Chen L, Petrelli R, Olesiak M, Wilson DJ, Labello NP, Pankiewicz KW: Bis(sulfonamide) isosters of mycophenolic adenine dinucleotide analogues: inhibition of inosine monophosphate dehydrogenase. Bioorg Med Chem. 2008 Aug 1;16(15):7462-9. doi: 10.1016/j.bmc.2008.06.003. Epub 2008 Jun 10. [18583139 ]

Target Details

10. Inosine-5'-monophosphate dehydrogenase 2

General Function:: Rna binding
Specific Function:: Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors.
Gene Name:: IMPDH2
Uniprot ID:: P12268
Molecular Weight:: 55804.495 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	>100 uM	Not Available	BindingDB 14487

References

Chen L, Petrelli R, Olesiak M, Wilson DJ, Labello NP, Pankiewicz KW: Bis(sulfonamide) isosters of mycophenolic adenine dinucleotide analogues: inhibition of inosine monophosphate dehydrogenase. Bioorg Med Chem. 2008 Aug 1;16(15):7462-9. doi: 10.1016/j.bmc.2008.06.003. Epub 2008 Jun 10. [18583139 ]

Target Details

11. Protein kinase C beta type

General Function:: Zinc ion binding
Specific Function:: Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity. Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A. In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. May participate in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis (By similarity). Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription.
Gene Name:: PRKCB
Uniprot ID:: P05771
Molecular Weight:: 76868.45 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	278 uM	Not Available	BindingDB 14487

References

Loog M, Uri A, Raidaru G, Jarv J, Ek P: Adenosine-5'-carboxylic acid peptidyl derivatives as inhibitors of protein kinases. Bioorg Med Chem Lett. 1999 May 17;9(10):1447-52. [10360754 ]

Adenosine (T3D4275)

Structure for T3D4275: Adenosine

Targets

Binding/Activity Constants

References

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References

References

Binding/Activity Constants

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Binding/Activity Constants

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Binding/Activity Constants

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Binding/Activity Constants

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