2006
DOI: 10.1194/jlr.m500349-jlr200
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Abstract: We have identified a series of potent cholesteryl ester transfer protein (CETP) inhibitors, one member of which, torcetrapib, is undergoing phase 3 clinical trials. In this report, we demonstrate that these inhibitors bind specifically to CETP with 1:1 stoichiometry and block both neutral lipid and phospholipid (PL) transfer activities. CETP preincubated with inhibitor subsequently bound both cholesteryl ester and PL normally; however, binding of triglyceride (TG) appeared partially reduced. Inhibition by torc… Show more

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Cited by 131 publications
(103 citation statements)
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References 45 publications
(48 reference statements)
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“…CETP contains several cysteine (Cys) residues of which Cys-13 is critically involved in its neutral sterol binding site [58]. Accordingly, JTT-705 does not inhibit transfer activity of a mutant CETP in which the cysteine 13 residue is replaced by serine [53], and CETP inhibitor action most likely involves the formation of a disulphide bond with Cys-13 of CETP [59]. Torcetrapib specifically binds to CETP with 1 : 1 stoichiometry and blocks the cholesteryl ester transfer-, as well as the triglyceride-and phospholipid transfer-promoting properties of CETP, but does not impair phosphatidylcholine transfer by PLTP [59].…”
Section: Cetp Inhibitors: Biochemical Properties and Mechanism Of Actionmentioning
confidence: 99%
“…CETP contains several cysteine (Cys) residues of which Cys-13 is critically involved in its neutral sterol binding site [58]. Accordingly, JTT-705 does not inhibit transfer activity of a mutant CETP in which the cysteine 13 residue is replaced by serine [53], and CETP inhibitor action most likely involves the formation of a disulphide bond with Cys-13 of CETP [59]. Torcetrapib specifically binds to CETP with 1 : 1 stoichiometry and blocks the cholesteryl ester transfer-, as well as the triglyceride-and phospholipid transfer-promoting properties of CETP, but does not impair phosphatidylcholine transfer by PLTP [59].…”
Section: Cetp Inhibitors: Biochemical Properties and Mechanism Of Actionmentioning
confidence: 99%
“…Torcetrapib acts by increasing the affi nity of CETP for HDLs ( 63 ). This generates a tight complex that reduces the amount of CETP available to promote transfers of cholesteryl esters and triglycerides between different lipoprotein particles.…”
Section: Torcetrapibmentioning
confidence: 99%
“…Tetrahydroquinoline derivatives have widely pharmaceuticals applications [12][13][14][15][16][17] . The reactions of tetrahydroquinoline with different derivatives, which lead to modification of its medicinal purpose [18][19][20] . Sulfonamides are known to have a widely applications in several biological systems [21][22][23][24][25] .…”
Section: Introductionmentioning
confidence: 99%