Erythrityl Tetranitrate

Identification

Name
Erythrityl Tetranitrate
Accession Number
DB01613
Type
Small Molecule
Groups
Approved
Description

A vasodilator with general properties similar to nitroglycerin. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1020)

Structure
Thumb
Synonyms
  • (2R*,3S)-rel-1,2,3,4-butanetetroltetranitrate
  • 1,2,3,4-Butanetetralyl tetranitrate
  • Eritrityl tetranitrate
  • Eritrityli tetranitras
  • Erythritol tetranitrate
  • Erythrol tetranitrate
  • ETN
  • Meso-erythritol tetranitrate
  • Tetranitrate d'eritrityle
  • Tetranitrato de eritritilo
  • Tetranitrin
  • Tetranitrol
External IDs
C01DA13 / NSC-106566
International/Other Brands
Cardilate
Categories
UNII
35X333P19D
CAS number
7297-25-8
Weight
Average: 302.11
Monoisotopic: 301.998221676
Chemical Formula
C4H6N4O12
InChI Key
SNFOERUNNSHUGP-ZXZARUISSA-N
InChI
InChI=1S/C4H6N4O12/c9-5(10)17-1-3(19-7(13)14)4(20-8(15)16)2-18-6(11)12/h3-4H,1-2H2/t3-,4+
IUPAC Name
(2S,3R)-1,3,4-tris(nitrooxy)butan-2-yl nitrate
SMILES
[O-][N+](=O)OC[[email protected]@H](O[N+]([O-])=O)[[email protected]](CO[N+]([O-])=O)O[N+]([O-])=O

Pharmacology

Indication

For the prevention of angina.

Structured Indications
Not Available
Pharmacodynamics

Erythrityl Tetranitrate is a vasodilator with general properties similar to nitroglycerin.

Mechanism of action

Similar to other nitrites and organic nitrates, erythrityl tetranitrate is converted to an active intermediate compound which activates the enzyme guanylate cyclase. This stimulates the synthesis of cyclic guanosine 3',5'-monophosphate (cGMP) which then activates a series of protein kinase-dependent phosphorylations in the smooth muscle cells, eventually resulting in the dephosphorylation of the myosin light chain of the smooth muscle fiber. The subsequent release of calcium ions results in the relaxation of the smooth muscle cells and vasodilation.

TargetActionsOrganism
AAtrial natriuretic peptide receptor 1
agonist
Human
AAtrial natriuretic peptide receptor 2
agonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Symptoms of overdose include increased intracranial pressure, with any or all of persistent throbbing headache, confusion, and moderate fever; Vertigo; Palpitations; Visual disturbances; Nausea and vomiting (possibly with colic and even bloody diarrhea); Syncope (especially in the upright posture); Air hunger and dyspnea, later followed by reduced ventilatory effort; Diaphoresis, with the skin either flushed or cold and clammy; Heart block and bradycardia; Paralysis; Coma; Seizures; Death.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
DapoxetineDapoxetine may increase the orthostatic hypotensive activities of Erythrityl Tetranitrate.Investigational
EthanolEthanol may increase the vasodilatory activities of Erythrityl Tetranitrate.Approved
MirodenafilMirodenafil may increase the vasodilatory activities of Erythrityl Tetranitrate.Investigational
MolsidomineMolsidomine may increase the hypotensive activities of Erythrityl Tetranitrate.Approved
RiociguatErythrityl Tetranitrate may increase the hypotensive activities of Riociguat.Approved
RosiglitazoneThe risk or severity of adverse effects can be increased when Erythrityl Tetranitrate is combined with Rosiglitazone.Approved, Investigational
SildenafilSildenafil may increase the vasodilatory activities of Erythrityl Tetranitrate.Approved, Investigational
TadalafilTadalafil may increase the vasodilatory activities of Erythrityl Tetranitrate.Approved, Investigational
UdenafilUdenafil may increase the vasodilatory activities of Erythrityl Tetranitrate.Approved, Investigational
VardenafilVardenafil may increase the vasodilatory activities of Erythrityl Tetranitrate.Approved
Food Interactions
  • Avoid alcohol.
  • Take on empty stomach: 1 hour before or 2 hours after meals.

References

Synthesis Reference
Not Available
General References
Not Available
External Links
Human Metabolome Database
HMDB15551
PubChem Compound
5284553
PubChem Substance
46508990
ChemSpider
4447608
ChEBI
60072
ChEMBL
CHEMBL2107583
Therapeutic Targets Database
DAP001060
PharmGKB
PA164746528
ATC Codes
C01DA13 — Eritrityl tetranitrateC01DA63 — Eritrityl tetranitrate, combinations
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Not Available
MSDS
Not Available

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedTreatmentDe Novo Myelodysplastic Syndromes / Previously Treated Myelodysplastic Syndromes / Secondary Myelodysplastic Syndromes1
2CompletedTreatmentAccelerated Phase Chronic Myelogenous Leukemia / Blastic Phase Chronic Myelogenous Leukemia / Childhood Acute Lymphoblastic Leukemia in Remission / Childhood Acute Myeloid Leukemia in Remission / Childhood Chronic Myelogenous Leukemia / Childhood Myelodysplastic Syndromes / Chronic Phase Chronic Myelogenous Leukemia / De Novo Myelodysplastic Syndromes / Disseminated Neuroblastoma / Juvenile Myelomonocytic Leukemia / Previously Treated Childhood Rhabdomyosarcoma / Previously Treated Myelodysplastic Syndromes / Pulmonary Complications / Recurrent Childhood Acute Lymphoblastic Leukemia / Recurrent Childhood Acute Myeloid Leukemia / Recurrent Childhood Large Cell Lymphoma / Recurrent Childhood Lymphoblastic Lymphoma / Recurrent Childhood Rhabdomyosarcoma / Recurrent Childhood Small Noncleaved Cell Lymphoma / Recurrent Neuroblastoma / Recurrent Wilms Tumor and Other Childhood Kidney Tumors / Recurrent/Refractory Childhood Hodgkin Lymphoma / Relapsing Chronic Myelogenous Leukemia / Secondary Acute Myeloid Leukemia / Secondary Myelodysplastic Syndromes1
3Active Not RecruitingTreatmentPlaque Psoriasis / Psoriasis1
4CompletedTreatmentRheumatoid Arthritis1
4Enrolling by InvitationBasic ScienceRheumatoid Arthritis1
4Unknown StatusTreatmentArthritis / Rheumatoid Arthritis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)61 °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.195 mg/mLALOGPS
logP1.68ALOGPS
logP1.23ChemAxon
logS-3.2ALOGPS
pKa (Strongest Basic)-5.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area220.2 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity53.25 m3·mol-1ChemAxon
Polarizability20.27 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7733
Blood Brain Barrier+0.9089
Caco-2 permeable-0.5825
P-glycoprotein substrateNon-substrate0.7905
P-glycoprotein inhibitor INon-inhibitor0.6464
P-glycoprotein inhibitor IINon-inhibitor0.8955
Renal organic cation transporterNon-inhibitor0.835
CYP450 2C9 substrateNon-substrate0.9002
CYP450 2D6 substrateNon-substrate0.8936
CYP450 3A4 substrateNon-substrate0.5357
CYP450 1A2 substrateNon-inhibitor0.7871
CYP450 2C9 inhibitorNon-inhibitor0.7619
CYP450 2D6 inhibitorNon-inhibitor0.9081
CYP450 2C19 inhibitorNon-inhibitor0.6943
CYP450 3A4 inhibitorNon-inhibitor0.8885
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8212
Ames testAMES toxic0.8896
CarcinogenicityCarcinogens 0.6703
BiodegradationReady biodegradable0.9161
Rat acute toxicity2.7983 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5607
hERG inhibition (predictor II)Non-inhibitor0.9098
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as alkyl nitrates. These are organic compounds containing a nitrate that is O-linked to an alkyl group.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organic oxoanionic compounds
Sub Class
Organic nitrates
Direct Parent
Alkyl nitrates
Alternative Parents
Organic nitro compounds / Organic nitric acids and derivatives / Organooxygen compounds / Organic oxides / Organic nitrogen compounds / Hydrocarbon derivatives
Substituents
Alkyl nitrate / Organic nitro compound / Organic nitric acid or derivatives / Organic 1,3-dipolar compound / Allyl-type 1,3-dipolar organic compound / Organic nitrogen compound / Organic oxide / Hydrocarbon derivative / Organooxygen compound / Aliphatic acyclic compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
nitrate ester (CHEBI:60072)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Protein kinase activity
Specific Function
Receptor for the atrial natriuretic peptide NPPA/ANP and the brain natriuretic peptide NPPB/BNP which are potent vasoactive hormones playing a key role in cardiovascular homeostasis. Has guanylate ...
Gene Name
NPR1
Uniprot ID
P16066
Uniprot Name
Atrial natriuretic peptide receptor 1
Molecular Weight
118918.11 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Schroder H, Noack E: Structure-activity relationship of organic nitrates for activation of guanylate cyclase. Arch Int Pharmacodyn Ther. 1987 Dec;290(2):235-46. [PubMed:2895614]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Transmembrane signaling receptor activity
Specific Function
Receptor for the C-type natriuretic peptide NPPC/CNP hormone. Has guanylate cyclase activity upon binding of its ligand. May play a role in the regulation of skeletal growth.
Gene Name
NPR2
Uniprot ID
P20594
Uniprot Name
Atrial natriuretic peptide receptor 2
Molecular Weight
117020.97 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Lange K, Koenig A, Roegler C, Seeling A, Lehmann J: NO donors. Part 18: Bioactive metabolites of GTN and PETN--synthesis and vasorelaxant properties. Bioorg Med Chem Lett. 2009 Jun 1;19(11):3141-4. doi: 10.1016/j.bmcl.2008.04.057. Epub 2008 Apr 26. [PubMed:19406636]

Drug created on August 29, 2007 14:04 / Updated on October 02, 2017 05:01