Halofuginone

Halofuginone
Ball-and-stick model of the halofuginone molecule
Clinical data
Trade namesHalocur
AHFS/Drugs.comInternational Drug Names
ATCvet code
Legal status
Legal status
  • EU: Rx-only
Identifiers
IUPAC name
  • 7-Bromo-6-chloro-3-[3-[(2S,3R)-3-hydroxy-2-piperidinyl]-2-oxopropyl]-4-quinazolinone
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC16H17BrClN3O3
Molar mass414.68 g·mol−1
3D model (JSmol)
SMILES
  • O=C(CN3C=NC2=CC(Br)=C(Cl)C=C2C3=O)C[C@@H]1NCCC[C@H]1O
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+/m0/s1 ☒N
  • Key:LVASCWIMLIKXLA-LSDHHAIUSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

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).[1] 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.[2]

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.[3] Halofuginone therefore has potential for the treatment of autoimmune disorders.[4]

Halofuginone is also an inhibitor of collagen type I gene expression and as a consequence it may inhibit tumor cell growth.[1] 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.[5]

References

  1. 1 2 "Halofuginone hydrobromide". NCI Drug Dictionary. National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services.
  2. ↑ "Halofuginone Receives FDA Orphan Drug Status For Scleroderma". WebCite. 10 March 2000. Archived from the original on 12 September 2012.
  3. ↑ Sundrud MS, Koralov SB, Feuerer M, Calado DP, Kozhaya AE, Rhule-Smith A, et al. (June 2009). "Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response". Science. 324 (5932): 1334–8. Bibcode:2009Sci...324.1334S. doi:10.1126/science.1172638. PMC 2803727. PMID 19498172.
  4. ↑ 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 (June 2009). "Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response". Science. 324 (5932): 1334–8. Bibcode:2009Sci...324.1334S. doi:10.1126/science.1172638. PMC 2803727. PMID 19498172. Lay summary – EurekAlert!. {{cite journal}}: Cite uses deprecated parameter |lay-url= (help)
  5. ↑ Keller TL, Zocco D, Sundrud MS, Hendrick M, Edenius M, Yum J, et al. (February 2012). "Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase". Nature Chemical Biology. 8 (3): 311–7. doi:10.1038/nchembio.790. PMC 3281520. PMID 22327401.
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