Halofuginone

Halofuginone, also known as RU-19110, is 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.

Product information

CAS Number: 55837-20-2

Molecular Weight: 414.68

Formula: C16H17BrClN3O3

Synonym:

RU 19110

Tempostatin

Chemical Name: 7-bromo-6-chloro-3-(3-((2S,3R)-3-hydroxypiperidin-2-yl)-2-oxopropyl)quinazolin-4(3H)-one.

Smiles: O[C@@H]1CCCN[C@H]1CC(=O)CN1C=NC2=CC(Br)=C(Cl)C=C2C1=O

InChiKey: LVASCWIMLIKXLA-LSDHHAIUSA-N

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

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Halofuginone competitively inhibits prolyl-tRNA synthetase by occupying both the prolineand tRNA-binding pockets of prolyl-tRNA synthetase. The IC50s of Halofuginone (1, 10, 100, 1000, 10000 nM; 48 hours) are 114.6 and 58.9 nM in KYSE70 and A549 cells, respectively. The IC50s of Halofuginone (1, 10, 100, 1000 nM; 24 hours) for NRF2 protein are 22.3 and 37.2 nM in KYSE70 and A549 cells, respectively. The IC50 of Halofuginone for global protein synthesis is 22.6 and 45.7 nM in KYSE70 and A549 cells, respectively.

In Vivo:

Halofuginone (0.2, 0.5, 1 or 2.5 mg/kg; injected intraperitoneally every other day for 1 month) attenuates progression of OA in anterior cruciate ligament transection (ACLT) mice. Lower concentration (0.2 or 0.5 mg/kg) has minimal effects on subchondral bone and higher concentration (2.5 mg/kg) induces proteoglycan loss in articular cartilage. Halofuginone (0.25 mg/kg; intraperitoneally injected; every day; 16 days) decreases NRF2 protein levels in tumors. While the tumor volumes do not change substantially between treatments with the vehicle, Halofuginone (0.25 mg/kg, intraperitoneally injected, every day) or cisplatin alone. Combined treatment with Halofuginone and Cisplatin significantly suppresses the tumor volume compared to treatment with Halofuginone or cisplatin alone.

References:

1. Pines M, Spector I. Halofuginone - The Multifaceted Molecule. Molecules. 2015 Jan 5;20(1):573-594. Review. PubMed PMID: 25569515.
2. Pines M. Halofuginone for fibrosis, regeneration and cancer in the gastrointestinal tract. World J Gastroenterol. 2014 Oct 28;20(40):14778-86. doi: 10.3748/wjg.v20.i40.14778. PubMed PMID: 25356039; PubMed Central PMCID: PMC4209542.
3. Bodanovsky A, Guttman N, Barzilai-Tutsch H, Genin O, Levy O, Pines M, Halevy O. Halofuginone improves muscle-cell survival in muscular dystrophies. Biochim Biophys Acta. 2014 Jul;1843(7):1339-47. doi: 10.1016/j.bbamcr.2014.03.025. Epub 2014 Apr 2. PubMed PMID: 24703880.

Products are for research use only. Not for human use.