halofuginone

{{Short description|Chemical compound}}

{{Use dmy dates|date=December 2024}}

{{cs1 config |name-list-style=vanc |display-authors=6}}

{{Drugbox

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| verifiedrevid = 444144628

| image = Halofuginone.png

| width = 180

| image2 = Halofuginone molecule ball.png

| width2 = 240

| alt2 = Ball-and-stick model of the halofuginone molecule

| tradename = Halocur

| Drugs.com = {{drugs.com|international|halofuginone}}

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| ATCvet = yes

| ATC_prefix = P51

| ATC_suffix = BX01

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| legal_EU = Rx-only

| legal_EU_comment = {{cite web | title=Halocur EPAR | website=European Medicines Agency (EMA) | date=29 October 1999 | url=https://www.ema.europa.eu/en/medicines/veterinary/EPAR/halocur | access-date=26 December 2024}}{{cite web | title=Halocur PI | website=Union Register of medicinal products | date=9 November 1999 | url=https://ec.europa.eu/health/documents/community-register/html/v013.htm | access-date=26 December 2024}}

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| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 55837-20-2

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| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 1199540

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = L31MM1385E

| PubChem = 400772

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 355164

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 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+/m0/s1

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = LVASCWIMLIKXLA-LSDHHAIUSA-N

| IUPAC_name = 7-Bromo-6-chloro-3-[3-[(2S,3R)-3-hydroxy-2-piperidinyl]-2-oxopropyl]-4-quinazolinone

| C=16 | H=17 | Br=1 | Cl=1 | N=3 | O=3

| smiles = O=C(CN3C=NC2=CC(Br)=C(Cl)C=C2C3=O)C[C@@H]1NCCC[C@H]1O

|drug_name=|alt=|caption=|type=|MedlinePlus=|licence_EU=|licence_US=}}

Halofuginone, sold under the brand name Halocur, is a coccidiostat used in veterinary medicine. It is a synthetic halogenated derivative of febrifugine, a natural quinazolinone alkaloid which can be found in the Chinese herb Dichroa febrifuga (Chang Shan).{{cite web | url = http://www.cancer.gov/drugdictionary/?CdrID=38485 | title = Halofuginone hydrobromide | work = NCI Drug Dictionary | publisher = National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services }} Collgard Biopharmaceuticals is developing halofuginone for the treatment of scleroderma and it has received orphan drug designation from the U.S. Food and Drug Administration.{{cite web | url = http://www.pslgroup.com/dg/18dff6.htm | title = Halofuginone Receives FDA Orphan Drug Status For Scleroderma | archive-url = https://web.archive.org/web/20120304235043/http://www.pslgroup.com/dg/18dff6.htm | archive-date= 4 March 2012 | url-status = dead | date = 10 March 2000 | work = WebCite }}

Halofuginone inhibits the development of T helper 17 cells, immune cells that play an important role in autoimmune disease, but it does not affect other kinds of T cells which are involved in normal immune function.{{cite journal | vauthors = 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 | display-authors = 6 | title = Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response | journal = Science | volume = 324 | issue = 5932 | pages = 1334–8 | date = June 2009 | pmid = 19498172 | pmc = 2803727 | doi = 10.1126/science.1172638 | bibcode = 2009Sci...324.1334S }} Halofuginone therefore has potential for the treatment of autoimmune disorders.

Halofuginone is also an inhibitor of collagen type I gene expression and as a consequence it may inhibit tumor cell growth. Halofuginone exerts its effects by acting as a high affinity inhibitor of the enzyme glutamyl-prolyl tRNA synthetase. Inhibition of prolyl tRNA charging leads to the accumulation of uncharged prolyl tRNAs, which serve as a signal to initiate the amino acid starvation response, which in turn exerts anti-inflammatory and anti-fibrotic effects.{{cite journal | vauthors = 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 | display-authors = 6 | title = Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase | journal = Nature Chemical Biology | volume = 8 | issue = 3 | pages = 311–7 | date = February 2012 | pmid = 22327401 | pmc = 3281520 | doi = 10.1038/nchembio.790 }}