Halofuginone

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Halofuginone
Halofuginone2DACS.svg
Ball-and-stick model of the halofuginone molecule
Systematic (IUPAC) name
7-Bromo-6-chloro-3-[3-[(2S,3R)-3-hydroxy-2-piperidinyl]-2-oxopropyl]-4-quinazolinone
Clinical data
AHFS/Drugs.com International Drug Names
Identifiers
CAS Registry Number 55837-20-2 YesY
ATCvet code QP51AX08
PubChem CID: 400772
ChemSpider 355164 N
UNII L31MM1385E YesY
ChEMBL CHEMBL1199540 N
Chemical data
Formula C16H17BrClN3O3
Molecular mass 414.68 g/mol
 N (what is this?)  (verify)

Halofuginone 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[edit]

  1. ^ a b Halofuginone hydrobromide, NCI Drug Dictionary
  2. ^ Halofuginone Receives FDA Orphan Drug Status For Scleroderma, March 10, 2000
  3. ^ Sundrud, M. S.; Koralov, S. B.; Feuerer, M.; Calado, D. P.; Kozhaya, A. E.; Rhule-Smith, A.; Lefebvre, R. E.; Unutmaz, D.; Mazitschek, R. (2009). "Halofuginone Inhibits TH17 Cell Differentiation by Activating the Amino Acid Starvation Response". Science 324 (5932): 1334–8. doi:10.1126/science.1172638. PMC 2803727. PMID 19498172. 
  4. ^ A new lead for autoimmune disease: A small-molecule drug inhibits Th17 cells, eases symptoms in mouse model, June 4, 2009
  5. ^ Keller et al (2012) Halofuginone and other febrifugine derivatives inhibit prolyl-trna synthetase. Nature Chemical Biology 12;8(3):311-7. doi: 10.1038/nchembio.790.