BCX 1470

IC50: FD 96 nM, C1 1.6 nM
C1s is an 80-kDa serine protease that mediates the proteolytic activity of the C1 complex by cleaving C2 and C4 both. BCX-1470, discovered in 1997 as a FD inhibitor (IC50=96 nM), was further found to be a very potent C1s inhibitor (IC50=1.6 nM).
In vitro: BCX-1470 has the highest inhibitory activity of Factor D, with an IC50 of approx. 100 nM, which is two orders higher than the inhibitory activity of another commercially available general protease inhibitor, named FUT-175, when inhibting FD [1].
In vivo: BCX-1470 has been shown to be safe in animal toxicity studies and has blocked the development of reverse-passive Arthus reactioninduced oedema in rats [1].
Clinical trial: BCX-1470 has also been tested for safety in clinical trials with healthy volunteers but the outcome of these trials have not officially been published. Whereas no further clinical trials have been reported, a recent patent might indicate a future usage of the compound in the treatment of AMD. It suggests that BCX-1470 would be a candidate therapeutic for complement activation during cardiopulmonary bypass surgery
Reference:
[1] Morikis D, Lambris JD. Structural aspects and design of low-molecular-mass complement inhibitors. Biochem Soc Trans. 2002;30(Pt 6):1026-36.

The Arthus reaction in rodents: species-specific requirement of complement.[Pubmed:10605043]

J Immunol. 2000 Jan 1;164(1):463-8.

We induced reverse passive Arthus (RPA) reactions in the skin of rodents and found that the contribution of complement to immune complex-mediated inflammation is species specific. Complement was found to be necessary in rats and guinea pigs but not in C57BL/6J mice. In rats, within 4 h after initiation of an RPA reaction, serum alternative pathway hemolytic titers decreased significantly below basal levels, whereas classical pathway titers were unchanged. Thus the dermal reaction proceeds coincident with systemic activation of complement. The serine protease inhibitor BCX 1470, which blocks the esterolytic and hemolytic activities of the complement enzymes Cls and factor D in vitro, also blocked development of RPA-induced edema in the rat. These data support the proposal that complement-mediated processes are of major importance in the Arthus reaction in rats and guinea pigs, and suggest that BCX 1470 will be useful as an anti-inflammatory agent in diseases where complement activation is known to be detrimental.

BCX 1470 inhibits the esterolytic activity of factor D (IC50=96 nM) and C1s (IC50=1.6 nM), 3.4- and 200-fold better, respectively, than that of trypsin.

BCX 1470,217099-43-9,Thrombin inhibitor,Natural Products,Serine Protease, buy BCX 1470 , BCX 1470 supplier , purchase BCX 1470 , BCX 1470 cost , BCX 1470 manufacturer , order BCX 1470 , high purity BCX 1470