Identification

Name
FG-2216
Accession Number
DB08687  (DB05577)
Type
Small Molecule
Groups
Investigational
Description

A orally active prolyl-hydroxylase inhibitor which can stabilize hypoxia-inducible transcription factor independent of oxygen availability. [1]

Structure
Thumb
Synonyms
  • (((1-Chloro-4-hydroxyisoquinolin-3-yl)carbonyl)amino)acetic acid
  • 1-Chloro-N- (hydroxyformylmethyl-4-hydroxyisoquinoline-3-carboxamide
  • 1-Chloro-N-(hydroxyformylmethyl-4-hydroxyisoquinoline-3-carboxamide
Categories
Not Available
UNII
RU921DS4Z5
CAS number
223387-75-5
Weight
Average: 280.664
Monoisotopic: 280.025084493
Chemical Formula
C12H9ClN2O4
InChI Key
OUQVKRKGTAUJQA-UHFFFAOYSA-N
InChI
InChI=1S/C12H9ClN2O4/c13-11-7-4-2-1-3-6(7)10(18)9(15-11)12(19)14-5-8(16)17/h1-4,18H,5H2,(H,14,19)(H,16,17)
IUPAC Name
2-[(1-chloro-4-hydroxyisoquinolin-3-yl)formamido]acetic acid
SMILES
OC(=O)CNC(=O)C1=C(O)C2=CC=CC=C2C(Cl)=N1

Pharmacology

Indication

Investigated for use/treatment in anemia and kidney disease.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UEgl nine homolog 1Not AvailableHuman
UHypoxia-inducible factor 1-alphaNot AvailableHuman
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
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Bernhardt WM, Wiesener MS, Scigalla P, Chou J, Schmieder RE, Gunzler V, Eckardt KU: Inhibition of prolyl hydroxylases increases erythropoietin production in ESRD. J Am Soc Nephrol. 2010 Dec;21(12):2151-6. doi: 10.1681/ASN.2010010116. Epub 2010 Nov 29. [PubMed:21115615]
External Links
PubChem Compound
6914666
PubChem Substance
99445158
ChemSpider
5290544
BindingDB
50193145
ChEMBL
CHEMBL426560
HET
UN9
PDB Entries
2hbt / 2hbu / 2y33 / 2y34 / 3hqu / 4bqx / 4csw / 4ie6 / 4nhm / 4nj4
show 7 more

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.167 mg/mLALOGPS
logP2.39ALOGPS
logP1.85ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)3.18ChemAxon
pKa (Strongest Basic)-0.13ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area99.52 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity67.89 m3·mol-1ChemAxon
Polarizability25.94 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.6162
Blood Brain Barrier-0.6658
Caco-2 permeable-0.7285
P-glycoprotein substrateSubstrate0.5943
P-glycoprotein inhibitor INon-inhibitor0.9682
P-glycoprotein inhibitor IINon-inhibitor0.9776
Renal organic cation transporterNon-inhibitor0.9273
CYP450 2C9 substrateNon-substrate0.8352
CYP450 2D6 substrateNon-substrate0.8281
CYP450 3A4 substrateNon-substrate0.5999
CYP450 1A2 substrateInhibitor0.561
CYP450 2C9 inhibitorNon-inhibitor0.8612
CYP450 2D6 inhibitorNon-inhibitor0.8606
CYP450 2C19 inhibitorNon-inhibitor0.8949
CYP450 3A4 inhibitorNon-inhibitor0.9227
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7988
Ames testNon AMES toxic0.8649
CarcinogenicityNon-carcinogens0.8786
BiodegradationNot ready biodegradable0.9939
Rat acute toxicity2.4427 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9637
hERG inhibition (predictor II)Non-inhibitor0.7392
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 n-acyl-alpha amino acids. These are compounds containing an alpha amino acid which bears an acyl group at its terminal nitrogen atom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
N-acyl-alpha amino acids
Alternative Parents
Isoquinolines and derivatives / Pyridinecarboxylic acids and derivatives / 2-heteroaryl carboxamides / 2-halopyridines / Hydroxypyridines / Aryl chlorides / Benzenoids / Heteroaromatic compounds / Vinylogous acids / Secondary carboxylic acid amides
show 9 more
Substituents
N-acyl-alpha-amino acid / Isoquinoline / Pyridine carboxylic acid or derivatives / 2-heteroaryl carboxamide / 2-halopyridine / Hydroxypyridine / Aryl chloride / Aryl halide / Pyridine / Benzenoid
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Details
1. Egl nine homolog 1
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Peptidyl-proline dioxygenase activity
Specific Function
Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific prol...
Gene Name
EGLN1
Uniprot ID
Q9GZT9
Uniprot Name
Egl nine homolog 1
Molecular Weight
46020.585 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Ubiquitin protein ligase binding
Specific Function
Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transp...
Gene Name
HIF1A
Uniprot ID
Q16665
Uniprot Name
Hypoxia-inducible factor 1-alpha
Molecular Weight
92669.595 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Drug created on September 15, 2010 15:33 / Updated on January 23, 2018 12:19