Details
| Stereochemistry | RACEMIC |
| Molecular Formula | C16H17BrClN3O3.C3H6O3 |
| Molecular Weight | 504.759 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 2 / 3 |
| E/Z Centers | 0 |
| Charge | 0 |
| Stereo Comments | C16 H17 Br Cl N3 O3 |
SHOW SMILES / InChI
SMILES
CC(O)C(O)=O.O[C@H]1CCCN[C@@H]1CC(=O)CN2C=NC3=CC(Br)=C(Cl)C=C3C2=O
InChI
InChIKey=GATQERNJKZPJNX-LIOBNPLQSA-N
InChI=1S/C16H17BrClN3O3.C3H6O3/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;1-2(4)3(5)6/h5-6,8,14-15,19,23H,1-4,7H2;2,4H,1H3,(H,5,6)/t14-,15+;/m1./s1
DescriptionCurator's Comment: description was created based on several sources, including
http://musculardystrophynews.com/2016/01/12/grunenthal-and-akashi-
therapeutics-inc-announce-joint-drug-development-program-for-ht-100-in-the-treatment-of-patients-with-duchenne-muscular-dystrophy-dmd/
Curator's Comment: description was created based on several sources, including
http://musculardystrophynews.com/2016/01/12/grunenthal-and-akashi-
therapeutics-inc-announce-joint-drug-development-program-for-ht-100-in-the-treatment-of-patients-with-duchenne-muscular-dystrophy-dmd/
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. 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. Also was shown that halofuginone increased apoptosis in α smooth muscle actin- and prolyl 4-hydroxylase β-expressing cells in mdx diaphragm and in myofibroblasts, the major source of extracellular matrix. The profound antitumoral effect of halofuginone is attributed to its combined inhibition of tumour-stromal support, vascularization, invasiveness, and cell proliferation. HT-100 (delayed-release halofuginone), currently in clinical phase 1b/2a in five U.S. hospitals, is a small molecule drug candidate taken orally for the treatment of Duchenne muscular dystrophy (DMD) patients primarily through its ability to reduce fibrosis and inflammation and promote muscle fiber regeneration. The medicine candidate has been granted orphan drug designation in the U.S. and the EU — meaning it has been commercially undeveloped due to its limited profitability — and fast-track designation in the U.S. — an FDA process that aims to facilitate the development and patients’ reach to novel therapies for unmet medical needs.
Approval Year
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
0.54 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16815702 |
0.5 mg 1 times / day multiple, oral dose: 0.5 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
HALOFUGINONE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
0.42 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16815702 |
0.5 mg 2 times / day multiple, oral dose: 0.5 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
HALOFUGINONE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
1.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16815702 |
2 mg 1 times / day multiple, oral dose: 2 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
HALOFUGINONE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
3.09 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16815702 |
3.5 mg 1 times / day multiple, oral dose: 3.5 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
HALOFUGINONE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
12.58 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16815702 |
0.5 mg 1 times / day multiple, oral dose: 0.5 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
HALOFUGINONE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
15.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16815702 |
0.5 mg 2 times / day multiple, oral dose: 0.5 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
HALOFUGINONE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
67.97 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16815702 |
2 mg 1 times / day multiple, oral dose: 2 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
HALOFUGINONE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
85.66 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16815702 |
3.5 mg 1 times / day multiple, oral dose: 3.5 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
HALOFUGINONE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
17.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16815702 |
0.5 mg 1 times / day multiple, oral dose: 0.5 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
HALOFUGINONE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
25 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16815702 |
0.5 mg 2 times / day multiple, oral dose: 0.5 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
HALOFUGINONE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
37 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16815702 |
2 mg 1 times / day multiple, oral dose: 2 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
HALOFUGINONE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
30.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16815702 |
3.5 mg 1 times / day multiple, oral dose: 3.5 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
HALOFUGINONE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Pharmacokinetics and tissue distribution of halofuginone (NSC 713205) in CD2F1 mice and Fischer 344 rats. | 2001 Nov |
|
| Halofuginone does not reduce fibrosis in bleomycin-induced lung injury. | 2002 Aug 23 |
|
| Hepatic fibrosis: from bench to bedside. | 2002 Dec |
|
| Inhibition of anastomotic intimal hyperplasia by a synthetic nonsulphated heparin-mimicking compound. | 2002 Fall |
|
| Effect of halofuginone on the development of tight skin (TSK) syndrome. | 2002 Jul |
|
| Angiogenesis in bladder cancer--prognostic marker and target for future therapy. | 2002 Jun |
|
| Growth inhibition of prostate cancer xenografts by halofuginone. | 2002 May 1 |
|
| Hepatitis C and liver fibrosis. | 2003 Jan |
|
| Prevalence and control of bovine cryptosporidiosis in German dairy herds. | 2003 Mar 25 |
|
| Development and validation of a method for the confirmation of halofuginone in chicken liver and eggs using electrospray tandem mass spectrometry. | 2003 May 5 |
|
| Examination of antimicrobial activity of selected non-antibiotic drugs. | 2004 Dec |
|
| Efficient and sensitive detection of residues of nine coccidiostats in egg and muscle by liquid chromatography-electrospray tandem mass spectrometry. | 2004 Dec 25 |
|
| The effect of halofuginone, a specific inhibitor of collagen type 1 synthesis, in the prevention of esophageal strictures related to caustic injury. | 2004 Feb |
|
| Halofuginone inhibits serum-stimulated pericardial tissue retraction in vitro. | 2004 Jul-Aug |
|
| Animal models of systemic sclerosis: insights into systemic sclerosis pathogenesis and potential therapeutic approaches. | 2004 Nov |
|
| Liquid chromatography-electrospray tandem mass spectrometric assay suitable for quantitation of halofuginone in plasma. | 2004 Oct 15 |
|
| Halofuginone inhibits angiogenesis and growth in implanted metastatic rat brain tumor model--an MRI study. | 2004 Sep-Oct |
|
| Drug-eluting stent: a review and update. | 2005 |
|
| Screening for the coccidiostats halofuginone and nicarbazin in egg and chicken muscle: development of an ELISA. | 2005 Feb |
|
| Incidence of residues of nine anticoccidials in eggs. | 2005 Nov |
|
| Deposition and depletion of five anticoccidials in eggs. | 2005 Sep 7 |
|
| Phase I and pharmacokinetic study of halofuginone, an oral quinazolinone derivative in patients with advanced solid tumours. | 2006 Aug |
|
| Halofuginone induces matrix metalloproteinases in rat hepatic stellate cells via activation of p38 and NFkappaB. | 2006 Jun 2 |
|
| Field study of the efficacy of halofuginone and decoquinate in the treatment of cryptosporidiosis in veal calves. | 2006 Nov 11 |
|
| Hydrodynamics based transfection in normal and fibrotic rats. | 2006 Oct 14 |
|
| Potential therapeutical effects of topical halofuginone hydrobromide in keloid management. | 2007 |
|
| Gene expression during chemically induced liver fibrosis: effect of halofuginone on TGF-beta signaling. | 2007 Apr |
|
| Inhibition of fibroblast to myofibroblast transition by halofuginone contributes to the chemotherapy-mediated antitumoral effect. | 2007 Feb |
|
| Evolving concepts of liver fibrogenesis provide new diagnostic and therapeutic options. | 2007 Jul 30 |
|
| Development and validation of a cell culture based assay for in vitro assessment of anticryptosporidial compounds. | 2007 Jun |
|
| Targeting liver myofibroblasts: a novel approach in anti-fibrogenic therapy. | 2008 Dec |
|
| Halofuginone upregulates the expression of heparanase in thioacetamide-induced liver fibrosis in rats. | 2008 Jun |
|
| Type I collagen expression contributes to angiogenesis and the development of deeply invasive cutaneous melanoma. | 2008 Mar 1 |
|
| An outbreak of cryptosporidiosis in a collection of Stone curlews (Burhinus oedicnemus) in Dubai. | 2008 Oct |
|
| Halofuginone has a beneficial effect on gentamicin-induced acute nephrotoxicity in rats. | 2009 |
|
| Halofuginone mediated protection against radiation-induced leg contracture. | 2009 Aug |
|
| Halofuginone prevents extracellular matrix deposition in diabetic nephropathy. | 2009 Feb 6 |
|
| Wound-healing modulation in upper airway stenosis-Myths and facts. | 2009 Jan |
|
| Combination of cell culture and quantitative PCR for screening of drugs against Cryptosporidium parvum. | 2009 Jun 10 |
|
| Effectiveness of topically applied halofuginone in management of subglottic stenosis in rats. | 2009 May |
|
| Anti-angiogenic effects of pterogynidine alkaloid isolated from Alchornea glandulosa. | 2009 May 22 |
|
| Validation of a multi-residue liquid chromatography-tandem mass spectrometry confirmatory method for 10 anticoccidials in eggs according to Commission Decision 2002/657/EC. | 2009 Nov 13 |
|
| Halofuginone, a specific inhibitor of collagen type 1 synthesis, ameliorates oxidant colonic damage in rats with experimental colitis. | 2010 Mar |
|
| Halofuginone enhances the radiation sensitivity of human tumor cell lines. | 2010 Mar 1 |
Patents
Sample Use Guides
Small molecule halofuginone (HF) (with a median inhibitory concentration (IC50) of 3.6 ± 0.4 nM) selectively inhibits mouse and human TH17 differentiation by activating a cytoprotective signaling pathway, the amino acid starvation response (AAR). Inhibition of TH17 differentiation by HF is rescued by the addition of excess amino acids and is mimicked by AAR activation after selective amino acid depletion. HF also induces the AAR in vivo and protects mice from TH17-associated experimental autoimmune encephalomyelitis
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EMA VETERINARY ASSESSMENT REPORTS |
HALAGON [AUTHORIZED]
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DBSALT002197
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46905589
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DTXSID701002535
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6ZO4HT041C
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300000018739
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ACTIVE MOIETY
SUBSTANCE RECORD
