Halofuginone

Halofuginone

180px
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 Number	55837-20-2 Y
ATCvet code	QP51AX08 (WHO)
PubChem	CID: 400772
ChemSpider	355164 N
UNII	L31MM1385E Y
ChEMBL	CHEMBL1199540 N
Chemical data
Formula	C16H17BrClN3O3
Molecular mass	414.68 g/mol
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 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). 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.

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. 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.