Description
Halofuginone hydrobromide (Halofuginone) is a specific collagen Type I inhibitor that antagonize or inhibit the development of new blood vessels, hence can prevent intimal hyperplasia at a vascular anastomosis. It is used in the treatment or prevention of coccidiosis in both humans and animals.
Chemical Properties
White to Off-White Solid
Uses
Halogenated derivative of Febrifugine. Halofuginone hydrobromide is used as an antiprotozoal (coccidiostat).
Definition
The hydrobromide salt of halofuginone, a semisynthetic quinazolinone alkaloid anticoccidial derived from the plant Dichroa febrifuga, with antifibrotic and potential antineoplastic activities. Halofuginone specifically inhibits collagen type I gene expression and matrix metalloproteinase 2 (MMP-2) gene expression, which may result in the suppression of angiogenesis, tumor stromal cell development, and tumor cell growth. These effects appear to be due to halofuginone-mediated inhibition of the collagen type I and MMP-2 promoters. Collagen type I and MMP-2 play important roles in fibro-proliferative diseases.
Biological Activity
Halofuginone hydrobromide is a high affinity competitive prolyl-tRNA synthetase inhibitor (Ki = 18.3 nM). Blocks expression of MMP2. Inhibits ECM invasion in vitro and lung metastasis by bladder cancer cells in mice. Inhibits the development of Th17-driven autoimmunity in a mouse model of multiple sclerosis by activating the amino acid response (AAR) pathway. Also antiparasitic.
Toxicology
Halofuginone HBr (Halofuginone hydrobromide) is toxic by inhalation, dermal and ocular routes and is very irritant to both the eye and the skin. It is considered also a skin sensitiser[1].
Mode of action
Halofuginone is an an ATP-dependent inhibitor prolyl-tRNA synthetase (Ki of 18.3 nM). Halofuginone attenuates osteoarthritis (OA) by inhibition of TGF-β activity. Blocks expression of MMP2 and inhibits ECM invasion in vitro and lung metastasis by bladder cancer cells in mice. Also inhibits the development of Th17-driven autoimmunity in a mouse model of multiple sclerosis by activating the amino acid response (AAR) pathway.
References
[1] Vasileios Bampidis, Giovanna Azimonti, Maria de Lourdes Bastos, et al. “Safety of a feed additive consisting of halofuginone hydrobromide (STENOROL?) for chickens for fattening and turkeys (Huvepharma N.V.).” EFSA Journal 20 12 (2022).
