Halofuginone
Identification
- Generic Name
- Halofuginone
- DrugBank Accession Number
- DB04866
- Background
Halofuginone 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. Collgard Biopharmaceuticals is developing halofuginone for the treatment of scleroderma and received orphan drug designation from the U.S. Food and Drug Administration in March, 2000.
- Type
- Small Molecule
- Groups
- Investigational, Vet approved
- Structure
- Weight
- Average: 414.681
Monoisotopic: 413.014181779 - Chemical Formula
- C16H17BrClN3O3
- Synonyms
- (+/-)-trans-7-bromo-6-chloro-3-(3-(3-hydroxy-2-piperidyl)-acetonyl)-4(3H)-quinazolinone
- Halofuginone
- External IDs
- HT-100
Pharmacology
- Indication
For the treatment of scleroderma, cancer, and restenosis.
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- Pharmacodynamics
Halofuginone, 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 action
Halofuginone 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.
Target Actions Organism UCollagen alpha-1(I) chain Not Available Humans U72 kDa type IV collagenase Not Available Humans - Absorption
Readily bioavailable and rapidly absorbed following oral administration.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
23.8 to 72.1 hours
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAlendronic acid The risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when Halofuginone is combined with Alendronic acid. Ambroxol The risk or severity of methemoglobinemia can be increased when Halofuginone is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Halofuginone is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when Halofuginone is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Halofuginone is combined with Benzyl alcohol. - Food Interactions
- Not Available
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Halofuginone hydrobromide PTC2969MV1 64924-67-0 SJUWEPZBTXEUMU-LIOBNPLQSA-N Halofuginone lactate 6ZO4HT041C 82186-71-8 GATQERNJKZPJNX-LIOBNPLQSA-N - International/Other Brands
- Halocur / Stenorol / Tempostatin
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This 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.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazanaphthalenes
- Sub Class
- Benzodiazines
- Direct Parent
- Quinazolines
- Alternative Parents
- Pyrimidones / Piperidines / Aryl bromides / Aryl chlorides / Benzenoids / Beta-amino ketones / Heteroaromatic compounds / Secondary alcohols / 1,2-aminoalcohols / Lactams show 7 more
- Substituents
- 1,2-aminoalcohol / Alcohol / Amine / Aromatic heteropolycyclic compound / Aryl bromide / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Beta-aminoketone show 21 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
- Protozoa
Chemical Identifiers
- UNII
- L31MM1385E
- CAS number
- 55837-20-2
- InChI Key
- LVASCWIMLIKXLA-CABCVRRESA-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-[(2R,3S)-3-hydroxypiperidin-2-yl]-2-oxopropyl}-3,4-dihydroquinazolin-4-one
- SMILES
- [H][C@]1(O)CCCN[C@]1([H])CC(=O)CN1C=NC2=C(C=C(Cl)C(Br)=C2)C1=O
References
- General References
- 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. [Article]
- Sundrud MS, Koralov SB, Feuerer M, Calado DP, Kozhaya AE, Rhule-Smith A, Lefebvre RE, Unutmaz D, Mazitschek R, Waldner H, Whitman M, Keller T, Rao A: Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response. Science. 2009 Jun 5;324(5932):1334-8. doi: 10.1126/science.1172638. [Article]
- Keller TL, Zocco D, Sundrud MS, Hendrick M, Edenius M, Yum J, Kim YJ, Lee HK, Cortese JF, Wirth DF, Dignam JD, Rao A, Yeo CY, Mazitschek R, Whitman M: Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase. Nat Chem Biol. 2012 Feb 12;8(3):311-7. doi: 10.1038/nchembio.790. [Article]
- External Links
- KEGG Drug
- D04413
- PubChem Compound
- 456390
- PubChem Substance
- 175426875
- ChemSpider
- 401856
- ChEMBL
- CHEMBL1199540
- ZINC
- ZINC000005784191
- PDBe Ligand
- HFG
- Wikipedia
- Halofuginone
- PDB Entries
- 4hvc / 4k88 / 4olf / 4q15 / 4ydq / 5f9z / 5xio / 5xip / 5xiq / 5znj … show 8 more
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 2 Completed Treatment AIDS-related Kaposi's Sarcoma / Recurrent Kaposi's Sarcoma 1 2 Terminated Treatment Duchenne Muscular Dystrophy (DMD) 2 1 Completed Treatment Unspecified Adult Solid Tumor, Protocol Specific 1 1, 2 Terminated Treatment Duchenne Muscular Dystrophy (DMD) 1
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
Property Value Source Water Solubility 0.114 mg/mL ALOGPS logP 1.38 ALOGPS logP 1.71 Chemaxon logS -3.6 ALOGPS pKa (Strongest Acidic) 14.59 Chemaxon pKa (Strongest Basic) 9.28 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 82 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 95.87 m3·mol-1 Chemaxon Polarizability 37.17 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9465 Blood Brain Barrier - 0.938 Caco-2 permeable - 0.7265 P-glycoprotein substrate Substrate 0.6967 P-glycoprotein inhibitor I Non-inhibitor 0.6713 P-glycoprotein inhibitor II Inhibitor 0.584 Renal organic cation transporter Non-inhibitor 0.6585 CYP450 2C9 substrate Non-substrate 0.78 CYP450 2D6 substrate Non-substrate 0.744 CYP450 3A4 substrate Substrate 0.5212 CYP450 1A2 substrate Inhibitor 0.5391 CYP450 2C9 inhibitor Inhibitor 0.5325 CYP450 2D6 inhibitor Non-inhibitor 0.7765 CYP450 2C19 inhibitor Inhibitor 0.5863 CYP450 3A4 inhibitor Inhibitor 0.5591 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7138 Ames test Non AMES toxic 0.7227 Carcinogenicity Non-carcinogens 0.8721 Biodegradation Not ready biodegradable 0.9869 Rat acute toxicity 2.3967 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.771 hERG inhibition (predictor II) Inhibitor 0.811
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0009000000-e257511af13c4a226cb2 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-03di-0214900000-99e1cdb3f5c96a1d5d96 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-002b-1109000000-a9c3a608e579ada2b0c3 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-03e9-4039100000-244f8afcf09b1ba92038 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-000t-4198100000-e6f90b65608e86d7e012 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-002f-7392000000-6ae3463b5a2210bd1c70 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 175.95998 predictedDeepCCS 1.0 (2019) [M+H]+ 178.31798 predictedDeepCCS 1.0 (2019) [M+Na]+ 184.5243 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- 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
- Uniprot Name
- Collagen alpha-1(I) chain
- Molecular Weight
- 138941.105 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- 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 rup...
- Gene Name
- MMP2
- Uniprot ID
- P08253
- Uniprot Name
- 72 kDa type IV collagenase
- Molecular Weight
- 73881.695 Da
References
- 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. [Article]
Drug created at October 19, 2007 23:34 / Updated at November 03, 2023 23:47