title: Different effects of compounds decreasing cholesteryl ester transfer protein activity on lipoprotein metabolism.
abstract: OBJECTIVE
  Review literature on the effect of decreasing cholesteryl ester transfer protein (CETP) activity through pharmacological inhibition or modulation in preclinical and clinical settings compared to human CETP deficiency on lipoprotein characteristics, HDL remodelling and function.
  
  
  RESULTS
  Torcetrapib, anacetrapib and dalcetrapib inhibited the heterotypic transfer of cholesteryl ester from HDL to LDL and/or VLDL with similar potency, although the potency of dalcetrapib was time dependent. Homotypic transfer of cholesteryl ester from HDL3 to HDL2 via recombinant human CETP was inhibited by torcetrapib and anacetrapib (CETP inhibitors, CETPi) but not by dalcetrapib (CETP modulator, CETPm). In a hamster model of reverse cholesterol transport, only dalcetrapib increased efflux of fecal sterols from macrophages to feces. In clinical studies, dose-responses of CETPi and CETPm demonstrate qualitative and quantitative changes in HDL and LDL particle composition and distribution.
  
  
  CONCLUSIONS
  Recent studies of the CETPi torcetrapib and anacetrapib and the CETPm dalcetrapib have shown differences in the resulting increase in HDL-cholesterol and in the level of HDL remodelling and potential for effective reverse cholesterol transport. Results from ongoing clinical outcomes studies with anacetrapib and dalcetrapib will clarify the relevance of CETP inhibition versus modulation towards HDL remodelling in the treatment of cardiovascular diseases.
authors.affiliation: Pharmaceuticals Division, F. Hoffmann-La Roche Ltd, Basel, Switzerland. eric_j.niesor@roche.com
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Niesor
mesh_terms: D000577:Amides; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002986:Clinical Trials as Topic; D004952:Esters; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D023303:Oxazolidinones / Q000494:pharmacology / Q000627:therapeutic use; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use; D013438:Sulfhydryl Compounds / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000577:Amides; D000924:Anticholesteremic Agents; D053480:Cholesterol Ester Transfer Proteins; D004952:Esters; D008075:Lipoproteins, HDL; D023303:Oxazolidinones; D011804:Quinolines; D013438:Sulfhydryl Compounds; C411602:dalcetrapib; C483909:torcetrapib; C530884:anacetrapib