HALOFUGINONE HYDROBROMIDE

Details

Stereochemistry	RACEMIC
Molecular Formula	C16H17BrClN3O3.BrH
Molecular Weight	495.593
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Br.O[C@H]1CCCN[C@@H]1CC(=O)CN2C=NC3=CC(Br)=C(Cl)C=C3C2=O

InChI

InChIKey=SJUWEPZBTXEUMU-LIOBNPLQSA-N

InChI=1S/C16H17BrClN3O3.BrH/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;1H/t14-,15+;/m1./s1

HIDE SMILES / InChI

Molecular Formula	BrH
Molecular Weight	80.912
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C16H17BrClN3O3
Molecular Weight	414.681
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24703880
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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Matrix metalloproteinase-2 13 Target ID: CHEMBL333 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11099465	Inhibitor 8297
Collagen alpha-1(I) chain 11 Target ID: P02452\|\|\|Q15176\|\|\|Q9UML6 Gene ID: 1277.0 Gene Symbol: COL1A1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/11099465	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Duchenne muscular dystrophy 19 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24703880	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	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	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

T_1/2

Value	Dose	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

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P0039TA	https://www.1pchem.com/search?query=1P0039TA
A2B Chem	AB51886	http://a2bchem.com/prod/AB51886
Alfa Chemistry	17395-31-2	http://www.alfa-chemistry.com/search.aspx?q=17395-31-2
Ambeed	A162412	http://www.ambeed.com/search/Search.html?keyword=A162412
Angene	AGN-PC-0SJRAP	http://www.angenechemical.com/productshow/AGN-PC-0SJRAP.html
AstaTech	42217	http://astatechinc.com/CPSResult.php?CRNO=42217
AstaTech	44055	http://astatechinc.com/CPSResult.php?CRNO=44055
BLD Pharm	BD132622	http://www.bldpharm.com/search/Search.html?keyword=BD132622
Cayman Chemical	13370	http://www.caymanchem.com/app/template/Product.vm/catalog/13370
Hairui	HR141501	http://www.hairuichem.com/en/product/search.do?q=HR141501
Hairui	HR142335	http://www.hairuichem.com/en/product/search.do?q=HR142335
KeyOrganics	AS-35193	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-35193
MolPort	MolPort-008-266-629	https://www.molport.com/shop/molecule-link/MolPort-008-266-629
MolPort	MolPort-044-561-164	https://www.molport.com/shop/molecule-link/MolPort-044-561-164
MuseChem	R005528	https://www.musechem.com/product/R005528.html
MuseChem	R051332	https://www.musechem.com/product/R051332.html
Selleck Chemicals	S8144	http://www.selleckchem.com/search.html?searchDTO.searchParam=S8144
Tetrahedron	TS09180	http://www.thsci.com/search.do?q=TS09180
Toronto Research Chemicals	H102500	https://www.trc-canada.com/product-detail/?CatNum=H102500
Wonderchem	WD04XKX	http://www.wonder-chem.com/search.html?text=WD04XKX
Wonderchem	WD06IPV	http://www.wonder-chem.com/search.html?text=WD06IPV
eMolecules	300127039	https://orderbb.emolecules.com/search/#?query=300127039
eMolecules	44463241	https://orderbb.emolecules.com/search/#?query=44463241
eMolecules	49264256	https://orderbb.emolecules.com/search/#?query=49264256
eMolecules	49853752	https://orderbb.emolecules.com/search/#?query=49853752
eMolecules	56972371	https://orderbb.emolecules.com/search/#?query=56972371
mcule	MCULE-6593934512	https://mcule.com/MCULE-6593934512/

PubMed

Title	Date	PubMed
Novel therapy in the treatment of scleroderma.	2001 Jan	11116279
Determination of halofuginone and amprolium in chicken muscle and egg by liquid chromatography.	2001 Jan-Feb	11234850
Pharmacokinetics and tissue distribution of halofuginone (NSC 713205) in CD2F1 mice and Fischer 344 rats.	2001 Nov	11761455
Reduction in dermal fibrosis in the tight-skin (Tsk) mouse after local application of halofuginone.	2001 Nov 1	11705455
Halofuginone does not reduce fibrosis in bleomycin-induced lung injury.	2002 Aug 23	12137906
Inhibition of anastomotic intimal hyperplasia by a synthetic nonsulphated heparin-mimicking compound.	2002 Fall	19649227
Angiogenesis in bladder cancer--prognostic marker and target for future therapy.	2002 Jun	12031871
Resistance to anticoccidial drugs of Dutch avian Eimeria spp. field isolates originating from 1996, 1999 and 2001.	2003 Aug	17585463
Halofuginone to treat fibrosis in chronic graft-versus-host disease and scleroderma.	2003 Jul	12869955
Prevalence and control of bovine cryptosporidiosis in German dairy herds.	2003 Mar 25	12623207
The production and characterisation of an antibody to detect the coccidiostat toltrazuril and its metabolite ponazuril.	2003 May	12790197
Smad3 as a mediator of the fibrotic response.	2004 Apr	15154911
Amelioration of radiation-induced fibrosis: inhibition of transforming growth factor-beta signaling by halofuginone.	2004 Apr 9	14732719
Efficient and sensitive detection of residues of nine coccidiostats in egg and muscle by liquid chromatography-electrospray tandem mass spectrometry.	2004 Dec 25	15556532
Halofuginone, an inhibitor of collagen synthesis by rat stellate cells, stimulates insulin-like growth factor binding protein-1 synthesis by hepatocytes.	2004 Feb	14739098
Halofuginone inhibits serum-stimulated pericardial tissue retraction in vitro.	2004 Jul-Aug	15363165
Animal models of systemic sclerosis: insights into systemic sclerosis pathogenesis and potential therapeutic approaches.	2004 Nov	15577614
Halofuginone can worsen liver fibrosis in bile duct obstructed rats.	2004 Oct	15482349
Liquid chromatography-electrospray tandem mass spectrometric assay suitable for quantitation of halofuginone in plasma.	2004 Oct 15	15358305
Halofuginone inhibits angiogenesis and growth in implanted metastatic rat brain tumor model--an MRI study.	2004 Sep-Oct	15548356
Screening for the coccidiostats halofuginone and nicarbazin in egg and chicken muscle: development of an ELISA.	2005 Feb	15824002
Incidence of residues of nine anticoccidials in eggs.	2005 Nov	16332635
Residue analysis for halofuginone in sturgeon muscle by immunoaffinity cleanup and liquid chromatography.	2005 Nov-Dec	16526445
Prevention of esophageal strictures in a caustic burn model using halofuginone, an inhibitor of collagen type I synthesis.	2005 Sep	16148708
Deposition and depletion of five anticoccidials in eggs.	2005 Sep 7	16131122
Inhibition of rat renal fibroblast proliferation by halofuginone.	2006	16735800
Halofuginone induces matrix metalloproteinases in rat hepatic stellate cells via activation of p38 and NFkappaB.	2006 Jun 2	16489207
Hydrodynamics based transfection in normal and fibrotic rats.	2006 Oct 14	17036386
Effect of halofuginone, a collagen alpha1(I) inhibitor, on wound healing in normal and irradiated skin: implication for hematopoietic stem cell transplantation.	2007	17622757
(2R,3S)-(+)- and (2S,3R)-(-)-Halofuginone lactate: synthesis, absolute configuration, and activity against Cryptosporidium parvum.	2007 Aug 1	17544270
Effects of halofuginone on fibrosis formation secondary to experimentally induced subglottic trauma.	2007 Feb	17277625
Evolving concepts of liver fibrogenesis provide new diagnostic and therapeutic options.	2007 Jul 30	17663771
Evaluation of endotoxaemia in the prognosis and treatment of scouring merino lambs.	2007 Mar	17305974
Focusing on fibrosis: halofuginone-induced functional improvement in the mdx mouse model of Duchenne muscular dystrophy.	2008 Apr	18310507
Targeting liver myofibroblasts: a novel approach in anti-fibrogenic therapy.	2008 Dec	19669316
An outbreak of cryptosporidiosis in a collection of Stone curlews (Burhinus oedicnemus) in Dubai.	2008 Oct	18798028
Halofuginone has a beneficial effect on gentamicin-induced acute nephrotoxicity in rats.	2009	19793022
Wound-healing modulation in upper airway stenosis-Myths and facts.	2009 Jan	18767172
Combination of cell culture and quantitative PCR for screening of drugs against Cryptosporidium parvum.	2009 Jun 10	19342176
Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response.	2009 Jun 5	19498172
Treatment of calf diarrhea: antimicrobial and ancillary treatments.	2009 Mar	19174285
Synthesis and comparison of antimalarial activity of febrifugine derivatives including halofuginone.	2009 May	19442220
Multi-residue confirmatory method for the determination of twelve coccidiostats in chicken liver using liquid chromatography tandem mass spectrometry.	2009 Nov 13	19481216
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	19442981
Systematic review and meta-analyses of the effects of halofuginone against calf cryptosporidiosis.	2009 Oct 1	19493580
Halofuginone, a specific inhibitor of collagen type 1 synthesis, ameliorates oxidant colonic damage in rats with experimental colitis.	2010 Mar	19390970
Halofuginone enhances the radiation sensitivity of human tumor cell lines.	2010 Mar 1	19713035

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Oral

In Vitro Use Guide

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

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:37:01 GMT 2023` Edited by `admin` on `Fri Dec 15 15:37:01 GMT 2023`
Record UNII	PTC2969MV1
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

HALOFUGINONE HYDROBROMIDE

Official Name

English

4(3H)-QUINAZOLINONE, 7-BROMO-6-CHLORO-3-(3-(3-HYDROXY-2-PIPERIDINYL)-2-OXOPROPYL)-, HBR, TRANS-(±)-

Common Name

English

HALOFUGINONE HYDROBROMIDE [MART.]

Common Name

English

HALOFUGINONE HYDROBROMIDE [MI]

Common Name

English

NSC-713205

Code

English

(±)-TRANS-7-BROMO-6-CHLORO-3-(3-(3-HYDROXY-2-PIPERIDYL)-ACETONYL)-4(3H)-QUINAZOLINONE MONOHBR

Common Name

English

4(3H)-QUINAZOLINONE, 7-BROMO-6-CHLORO-3-(3-(3-HYDROXY-2-PIPERIDINYL)-2-OXOPROPYL)-, HYDROBROMIDE, TRANS-(±)-

Common Name

English

HALOFUGINONE HBR

Common Name

English

RU-19110

Code

English

(±)-TRANS-7-BROMO-6-CHLORO-3-(3-(3-HYDROXY-2-PIPERIDYL)-ACETONYL)-4(3H)-QUINAZOLINONE MONOHYDROBROMIDE

Systematic Name

English

STENOROL

Brand Name

English

HALOFUGINONE HYDROBROMIDE [USAN]

Common Name

English

HALOFUGINONE HYDROBROMIDE [GREEN BOOK]

Common Name

English

Classification Tree Code System Code

CFR

21 CFR 556.308