Halofuginone

ALK-0062

Halofuginone

55837-20-2

RU-19110

Halofuginone (RU-19110), a Febrifugine derivative, is a competitive prolyl-tRNA synthetase inhibitor with a Ki of 18.3 nM. Halofuginone is a specific inhibitor of type-I collagen synthesis and attenuates osteoarthritis (OA) by inhibition of TGF-β activity. Halofuginone is also a potent pulmonary vasodilator by activating Kv channels and blocking voltage-gated, receptor-operated and store-operated Ca2+ channels. Halofuginone has anti-malaria, anti-inflammatory, anti-cancer, anti-fibrosis effects.

Halofuginone

414.68

C16H17BrClN3O3

0.9978

Solid

DMSO : 20 mg/mL(48.23 mM;ultrasonic and adjust pH to 5 with HCl)

Plants >Saxifragaceae > Dichroa febrifugaLour

-20℃ for 3 years

Amebae Plasmodium

Room temperature in continental US; may vary elsewhere.

O=C1N(CC(C[C@@H]2NCCC[C@H]2O)=O)C=NC3=C1C=C(Cl)C(Br)=C3

Halofuginone attenuates progression of OA in anterior cruciate ligament transection (ACLT) mice. Lower concentration has minimal effects on subchondral bone and higher concentration (2.5 mg/kg) induces proteoglycan loss in articular cartilage. Halofuginone decreases NRF2 protein levels in tumors.

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. Halofuginone increases voltage-gated K+ (Kv) currents in pulmonary artery smooth muscle cells (PASMC) and K+ currents through KCNA5 channels in HEK cells transfected with KCNA5 gene. Halofuginone (0.03-1μM) inhibits receptor-operated Ca2+ entry (ROCE) in HEK cells transfected with calcium-sensing receptor gene and attenuates store-operated Ca2+ entry (SOCE) in PASMC.