References of Blood-coagulationfactor LACI (human clone lP9 protein moiety reduced), N-L-alanyl-
Title: Tissue Factor Pathway Inhibitor
Synonyms: TFPI; lipoprotein-associated coagulation inhibitor; LACI
Literature References: Endogenous inhibitor of the tissue factor mediated pathway of blood coagulation. Glycoprotein containing 276 amino acid residues; mol wt ~42 kDa. Structure consists of an acidic amino terminal region followed by three tandem Kunitz-type protease inhibitory domains and a basic carboxy terminal region. Forms a quaternary inhibitory complex with tissue factor, factor VIIa and factor Xa to block the formation of thrombin from prothrombin. Isoln of factor produced by hepatoma cells: G. J. Broze, Jr., J. P. Miletich,
Proc. Natl. Acad. Sci. USA 84, 1886 (1987); from human plasma: W. F. Novotny
et al., J. Biol. Chem. 264, 18832 (1989). Review of structure and physiology: G. J. Broze, Jr.,
Annu. Rev. Med. 46, 103-112 (1995); of pharmacology and therapeutic potential: A. K. Lindahl,
Cardiovasc. Res. 33, 286-291 (1997); B. Kaiser
et al., Emerg. Drugs 5, 73-87 (2000).
Derivative Type: Tifacogin
CAS Registry Number: 148883-56-1
CAS Name: N-L-Alanyl-blood coagulation factor LACI (human clone lP9 protein moiety reduced)
Manufacturers' Codes: SC-59735
Literature References: Recombinant human form; differs from the native protein by an additional alanine residue at the amino terminus and is not glycosylated. Prepn by expression in
E. coli: G. J. Broze, Jr.
et al., EP 318451;
eidem,
US 4966852 (1989, 1990 both to Monsanto Co.; Washington Univ.); M. E. Gustafson
et al., Protein Expression Purif. 5, 233 (1994). Production in
Saccharomyces cerevisiae: M. A. Innis, A. A. Creasey,
WO 9604377;
eidem,
US 6103500 (1996, 2000 both to Chiron). Clinical pharmacokinetics: M. J. B. Kemme
et al., Clin. Pharmacol. Ther. 67, 504 (2000). Clinical evaluation in sepsis: E. Abraham,
Crit. Care Med. 28, Suppl., S31 (2000).
Review: N. Sne
et al., IDrugs 5, 91-97 (2002).
Therap-Cat: Antithrombotic.
