Halofuginone

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

Clinical data
Trade names	Halocur
AHFS/Drugs.com	International Drug Names
ATCvet code	QP51BX01 (WHO)
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	55837-20-2 Y
PubChem CID	400772
ChemSpider	355164 N
UNII	L31MM1385E
ChEMBL	ChEMBL1199540 N
CompTox Dashboard (EPA)	DTXSID0048260
Chemical and physical data
Formula	C16H17BrClN3O3
Molar mass	414.68 g·mol−1
3D model (JSmol)	Interactive image
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
NY (what is this?)  (verify)

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. "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 4 March 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.

   • "A new lead for autoimmune disease". EurekAlert! (Press release). 4 June 2009.
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.