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Identification
NameHalofuginone
Accession NumberDB04866
TypeSmall Molecule
GroupsInvestigational, Vet Approved
DescriptionHalofuginone is a low molecular weight quinazolinone alkaloid, and a potent inhibitor of collagen alpha1(I) and matrix metalloproteinase 2 (MMP-2) gene expression. Halofuginone also effectively suppresses tumor progression and metastasis in mice.
Structure
Thumb
Synonyms
Tempostatin (Collgard Biopharmaceuticals)
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
StenorolNot Available
TempostatinNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Halofuginone hydrobromide
64924-67-0
Thumb
  • InChI Key: SJUWEPZBTXEUMU-UHFFFAOYNA-N
  • Monoisotopic Mass: 492.940344458
  • Average Mass: 495.593
DBSALT000462
Categories
UNIIL31MM1385E
CAS number55837-20-2
WeightAverage: 414.681
Monoisotopic: 413.014181779
Chemical FormulaC16H17BrClN3O3
InChI KeyLVASCWIMLIKXLA-YSSOQSIOSA-N
InChI
InChI=1S/C16H17BrClN3O3/c17-11-6-13-10(5-12(11)18)16(24)21(8-20-13)7-9(22)4-14-15(23)2-1-3-19-14/h5-6,8,14-15,19,23H,1-4,7H2/t14?,15-/m1/s1
IUPAC Name
7-bromo-6-chloro-3-{3-[(3R)-3-hydroxypiperidin-2-yl]-2-oxopropyl}-3,4-dihydroquinazolin-4-one
SMILES
O[C@@H]1CCCNC1CC(=O)CN1C=NC2=CC(Br)=C(Cl)C=C2C1=O
Pharmacology
IndicationFor the treatment of scleroderma, cancer, and restenosis.
Structured Indications Not Available
PharmacodynamicsHalofuginone, a fully synthetic small molecule, is a potent and selective regulator of stromal cell activation, cell migration and Collagen type I synthesis, a process that has been identified as a 'master switch' in the body's tissue repair process.
Mechanism of actionHalofuginone is a potent inhibitor of collagen a1(I) and matrix metalloproteinase 2 (MMP-2) gene expression. Halofuginone also suppresses extracellular matrix deposition and cell proliferation. The profound antitumoral effect of halofuginone is attributed to its combined inhibition of the tumor stromal support, vascularization, invasiveness, and cell proliferation.
TargetKindPharmacological actionActionsOrganismUniProt ID
Collagen alpha-1(I) chainProteinunknownNot AvailableHumanP02452 details
72 kDa type IV collagenaseProteinunknownNot AvailableHumanP08253 details
Related Articles
AbsorptionReadily bioavailable and rapidly absorbed following oral administration.
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half life23.8 to 72.1 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
  • Protozoa
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Halofuginone.Approved
AnvirzelAnvirzel may decrease the cardiotoxic activities of Halofuginone.Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Halofuginone.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Halofuginone.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Halofuginone.Approved, Investigational
DeslanosideDeslanoside may decrease the cardiotoxic activities of Halofuginone.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Halofuginone.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Halofuginone.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Halofuginone.Approved, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Halofuginone.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Halofuginone.Approved, Vet Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Halofuginone.Approved, Investigational
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Elkin M, Miao HQ, Nagler A, Aingorn E, Reich R, Hemo I, Dou HL, Pines M, Vlodavsky I: Halofuginone: a potent inhibitor of critical steps in angiogenesis progression. FASEB J. 2000 Dec;14(15):2477-85. [PubMed:11099465 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9465
Blood Brain Barrier-0.938
Caco-2 permeable-0.7265
P-glycoprotein substrateSubstrate0.6967
P-glycoprotein inhibitor INon-inhibitor0.6713
P-glycoprotein inhibitor IIInhibitor0.584
Renal organic cation transporterNon-inhibitor0.6585
CYP450 2C9 substrateNon-substrate0.78
CYP450 2D6 substrateNon-substrate0.744
CYP450 3A4 substrateSubstrate0.5212
CYP450 1A2 substrateInhibitor0.5391
CYP450 2C9 inhibitorInhibitor0.5325
CYP450 2D6 inhibitorNon-inhibitor0.7765
CYP450 2C19 inhibitorInhibitor0.5863
CYP450 3A4 inhibitorInhibitor0.5591
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7138
Ames testNon AMES toxic0.7227
CarcinogenicityNon-carcinogens0.8721
BiodegradationNot ready biodegradable0.9869
Rat acute toxicity2.3967 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.771
hERG inhibition (predictor II)Inhibitor0.811
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.114 mg/mLALOGPS
logP1.38ALOGPS
logP1.71ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)14.48ChemAxon
pKa (Strongest Basic)9.28ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area82 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity95.87 m3·mol-1ChemAxon
Polarizability37.59 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as quinazolines. These are compounds containing a quinazoline moiety, which is made up of two fused six-member aromatic rings, a benzene ring and a pyrimidine ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassNaphthyridines
Sub ClassQuinazolines
Direct ParentQuinazolines
Alternative Parents
Substituents
  • Quinazoline
  • Pyrimidone
  • Chlorobenzene
  • Bromobenzene
  • Benzenoid
  • Pyrimidine
  • Piperidine
  • Beta-aminoketone
  • Aryl halide
  • Aryl chloride
  • Aryl bromide
  • Heteroaromatic compound
  • Alpha-aminoketone
  • Secondary alcohol
  • Lactam
  • Ketone
  • 1,2-aminoalcohol
  • Azacycle
  • Secondary amine
  • Secondary aliphatic amine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organobromide
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Platelet-derived growth factor binding
Specific Function:
Type I collagen is a member of group I collagen (fibrillar forming collagen).
Gene Name:
COL1A1
Uniprot ID:
P02452
Molecular Weight:
138941.105 Da
References
  1. Elkin M, Miao HQ, Nagler A, Aingorn E, Reich R, Hemo I, Dou HL, Pines M, Vlodavsky I: Halofuginone: a potent inhibitor of critical steps in angiogenesis progression. FASEB J. 2000 Dec;14(15):2477-85. [PubMed:11099465 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Zinc ion binding
Specific Function:
Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly...
Gene Name:
MMP2
Uniprot ID:
P08253
Molecular Weight:
73881.695 Da
References
  1. Elkin M, Miao HQ, Nagler A, Aingorn E, Reich R, Hemo I, Dou HL, Pines M, Vlodavsky I: Halofuginone: a potent inhibitor of critical steps in angiogenesis progression. FASEB J. 2000 Dec;14(15):2477-85. [PubMed:11099465 ]
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Drug created on October 19, 2007 17:34 / Updated on December 08, 2016 11:11