17
Views
10
CrossRef citations to date
0
Altmetric
Research

Section Review: Cardiovascular and Renal: ACAT inhibitors in development

&
Pages 427-436 | Published online: 03 Mar 2008

References

  • GRUNDY SM: HMG-CoA reductase inhibitors for the treatment of hypercholesterolaemia. N Engl. J. Med. (1988) 319: 24.
  • VAHOUNY GV, TREADWELL CR: Changes in lipid com-position of lymph during cholesterol absorption in rat. Am.1 Physiol. (1957) 191: 179.
  • HEIDER JG, PICKENS CE, KELLY LA: Role of acyl CoA:cho-lesterol acyltransferase in cholesterol absorption and its inhibition by 57-118 in the rabbit. j. Lipid. Res. (1983) 24: 1127.
  • First demonstration that ACAT inhibitor, SaH 57–118, inhibits choles-terol absorption in cholesterol-fed rats.
  • BENNETT CS, TERCYAK AM: Reduced cholesterol trans-mucosal transport in rats with inhibited mucosal acyl CoA:cholesterol acyltransferase and normal pancreatic function. J. Lod Res. (1984) 25:148.
  • LARGIS EE, WANG CH, DE VRIES VG, SCHAFFER SA: CL-277082: A novel inhibitor of ACAT-catalyzed choles-terol esterification and cholesterol absorption. J. Lipid. Res. (1989) 30:681.
  • GOODMAN DS: Cholesterol ester metabolism. Pbysiol. Rev. (1965) 45:747.
  • CHANG TY, DOOLITTLE GM: Acylcoenzyme A:choles- terol O-acyltransferase. In: The Enzymes, Boyer PD (Ed), Academic Press. Inc. (1983) 16:523.
  • CHANG CCY, HUH HY, CADIGAN KM, CHANG TY: Molecu- lar cloning and functional expression of human acyl-CoA:cholesterol acyltransferase cDNA in mutant Chinese hamster ovary cells. J. Biol. Chem. (1993) 263:20747.
  • First report of human ACAT cDNA cloning.
  • SUCKLING ICE, STANGE EF: Role of acyl-CoA:cholesterol acyltransferase in cellular cholesterol metabolism. J. Lipid Res. (1985) 26:647.
  • An excellent comprehensive review of ACAT.
  • FUKUSHIMA H, AONO S, NAKATANI H: Effect of N-(alpha-methylbenzoyl) linoleamide on lipid levels of plasma and liver in cholesterol-fed rats. J. Nutr. (1968) 96:15.
  • FUICUSHIMA H, TOKI K, NAKATANI H: The effect of N-(alpha-methylbenzoyOlinoleamide on experimental atherosclerosis in rabbits. J. Atberoscler. Res. (1969) 9:57.
  • NATORI K, OKAZAKI Y, NAKAJIMA T, HIROHASH1 T, AONO S: Mechanism of the inhibition of cholesterol absorption lby DL-mplin2m Ulf- inhibition of cholesterol esterification. Jap. J. Pbarmacol. (1986) 42:517.
  • HIROHASHI A, NAGATA A, M1YAWAKI H, NAKATANI H, TOM K: Metabolism of linoleamidles. L Absorption, excretion and metabolism of N-(alpha-methylben-zoyl)Enoleamitle in rat and human. Xenobiotica (1976) 6:329.
  • WILLIAMS RJ, MCCARTHY AD, SUTHERLAND CD: Esterifi-cation and absorption of cholesterol: in vitro and in vivo observation in the rats. Blochim. Biophys. Ada. (1989) 1003:213.
  • HEIDER JG: Agents which inhibit cholesterol esterifica-tion in the intestine and their potential value in the treatment of hypercholesterolaemia. In: Pharmacologi-cal Control of Hyperlipidemia Fears R, Ed - Prous Science Pub 1986: 423.
  • TSE FL, JAFFE JM: Disposition of silicon-containing am-ide, an inhibitor of acyl-CoA:cholesterol acyltrans-ferase in dog and rat. Biopharmaceutics &Drug Dispusition (1987) 8:437.
  • DE VRIES VG, SCHAFFER SA, LARGIS EE, DUTLA MD, WANGCH, BLOOM JD, KATOCS AS: Potential an-tiatherosclerotic agents. 5. An acyl-CoAlcholesterol O-acyltransferase inhibitor with hypercholesterolemic activity. J. Med. Chem. (1986) 29:1131.
  • LARGIS EE, KATOCS AS, WANG CH, SCHAFFER SA: Effect of CL 277082 on cholesterol esterification in vitro and on cholesterol absorption in the rat. 7th International Symposium on Atherosclerosis, Melbourne (1985); A63. Hypocholesterolemic activity of CL 277082 in cholesterol-fed rats.
  • SCHNITZER-POLOKOFF R, SALISBURY B, COMPTON D, DAVID H: The effect of acyl-CoA:cholesterol acyltrans-ferase (ACAT) inhibition on cholesterol metabolism in rhesus monkeys. 9th Symposium on Atherosclerosis, Rosemont, USA (1991); A91.
  • SCHAFFER SA, BLOOM JD, DE VRIES VG, DUTIA AS, KATOCS AS, LARGIS EE: CL 277082, a novel inhibitor of cholesterol esterification and cholesterol absorption. Atherosclerosis VII (1986)Fidge NH, Nestel PJ (Eds) Excerpts Medica Pub, 633.
  • Hypocholesterolemic and anti-atherosclerotic activity of CL 277082 in cholesterol-fed rabbits.
  • HARRIS WS, DUJOVNE CA, BERBMANNK, NEAL J, AKESTER J, WINDSOR SL, GREENE D, LOOK Z: Effect of the ACATinhibitor on cholesterol metabolism in humans. din. Pharmacol. Ther. (1990) 48:189.
  • First disclosure of human data from clinical trials with CL 277082.
  • LARGIS EE, KATOCS AS: Trisubstituted ureas are potent inhibitors of ACAT and dietary cholesterol absorption. 10th International Symposium on Drugs Affecting Lpki Me-tabolism, Houston, USA. (1989) A314.
  • First disclosure of CL 283546.
  • BRYZINSKI BS: Pharmacological effects of the ACATInhibitor CL 283796. IBC's Second Annual Conference on Atherosclerosis, Philadelphia, USA. (1994).
  • ROARK WH, TRIVEDI BK, HOLMES A, ROTH BD, HOEFLE ML, KRAUSE BR, KIEFT K, STANFIELD RL: SAR studies on novel fatty add anilidie ACAT inhibitors. Am. Chem. Soc. 198 Meet. (1989): MEDI 71.
  • Synthesis and SAR of novel ACAT inhibitors.
  • KRAUSE BR, HOEFLE ML, HOLMES A: Lipid-regulating activity of PD 128042, a novel inhibitor of acyl CoA:cho-lesterol acyltransferase. 10th International Symposium on
  • Drugs Affecting Lipid Metabolism, Houston, USA (1989): 63. Hypocholesterolemic activity of PD 128042.
  • FIELD FJ, ALBRIGHT E, MATHUR S: Inhibition of acylcoen-zyme A:cholesterol acyltransferase activity by PD 128042: Effect on cholesterol metabolism and secretion in CaCo2 cells. Lipids (1991) 26 (1):1.
  • KRAUSE BR, ANDERSON M, BISGAIER CL, BOCAN T, BOUSLEY B, DEHART P, ESSENBURG A, HAMELEHLE K, HOMAN R, KIEFT K, MCNALLY W, STANFIELD R, NEWIONRS: In vivo evidence that the lipid-regulating activity of the ACAT inhibitor a-976 in rats is due to inhibition of both intestinal and liver ACAT. J. Lipid. Res. (1993) 34:279.
  • This study demonstrates that orally administered CI-976 inhibits both intestinal and hepatic ACAT.
  • KRAUSE BR, BOUSLEY R, ICIEFT K, STANFIELD R: Effectsof the ACAT inhibitor CI-976 on plasma cholesterol concentrations and distribution in hamsters fed zero and low-cholesterol diets. 9th International Symposium on Atherosclerosis, Rosemont, USA. (1991): A97.
  • BOCAN TMA, MUELLER SB, UHLENDORF PD, NEW ION RS, KRAUSE BR: Comparison of CI-976, an ACAT inhibitor,and selected lipid-lowering agents for anti-atherosderotic activity in iliac-femoral and thoracic aortic lesions. Arterioscler. Thromb. (1991) 11:1830.
  • The results of this study suggests the direct anti-atherosclerotic effect of CI-976 in the arterial wall in pre-established hypercholesterolemic rabbits.
  • BOCAN TMA, MUELLER SB, UHLENDORF PD, BROWN EQ, MAZURAND MJ, BLACK AE: Inhibition of acyl-CoA:cho-lesterol O-acyltransferase reduces the cholesteryl ester enrichment of atherosclerotic lesions in the Yucatan micropig. Athersckrosis (1993) 99:175.
  • The results of this study suggests the direct anti-atherosclerotic effect of CI-976 in the arterial wall in the Yucatan rnicropigs.
  • Warner-Lambert's ACAT inhibitor, C7–976 SCRIP (1990)1532:29.
  • KRAUSE BR, BLACK AE, BOUSLEY R, ESSENBURG A, COR- NICELLI J, HOLMES A, HOMAN R, KIEFT K, SEKERKE C, SHAW-HES MK, STANFIELD R, TRIVEDI B, WOOLF T: Divergent pharmacologic activities of PD 132301-2 and CL 277082, urea inhibitor of acyl-CoA:cholesterol acyl-transferase. J. Pharmacol. Exp. Ther. (1993) 267 (2):734.
  • Hypocholesterolemic activity of PD 132301–2 is compared with CL 277082 using several animal models.
  • DOMINICK MA, MCGUIRE EJ, REINDEL JF, BOBROWSKI WF, BOCAN TM, GOUGH AW: Subacute toxidty of a novelInhibitor of acyl-CoA:cholesterol acyltransferase in beagle dogs. Fundam. Appl. Toxicol. (1993) 4:105.
  • Detailed study of the subacute toxicity of PD 132301–2.
  • IIZUMI Y, YANAGITA Y, MASUYAMA Y, OHTSUKA H, ICAKUTA H, FUJIMURI N, ITOH N, MATSUDA K, OHATA I: Lipid-lowering and anti-atherosclerotic activity of YM17E, an inhibitor of acyl-CoA:cholesterol acyltrans-ferase in animal models. 9th International Symposium on Atherosclerosis, Rosemont, USA. (1991): A96.
  • First disclosure of YM17E.
  • YM17E. Drugs Future (1993) 18(9):813.
  • MATSUDA K: ACAT inhibitor as potent anti-atherosclerotic agent and SAR study of some urea derivatives. 13th Medicinal Chemistry Symposium, Osaka, Japan. (1992): 1–4.
  • First disclosure of YM750.
  • YM750. New Current (in Japanese) (1993) 4 (28): 50.
  • BILLHEIMER JT, CROMOLOY DA, HIGLEY CA, WFXLEY RR, ROBINSON CS, GIIIIFS PJ: The diarylthioimidazole, Dup 128, is a potent inhibitor of acyl-CoA:cholesterol acyl-transferase (ACAT). 9th International Symposium on Atherosclerosis, Rosemont, WA. (1991): A94.
  • First disclosure of Dup 128.
  • WILDE RG, BILLHEIMER JT, WEXLER RR: ACAT inhibitors with two heterocyclic substituents. Am. Chem. Soc. 206 Meet. (1993): MEDI 44.
  • GILLES PJ, ROBINSON CS, HIGLEY CA, WEXLER RR, BILL-HEIMER JT: Inhibition of intestinal acyl-CoA:cholesterol acyltransferase (ACAT) by Dup 128 in a cholesterol-fed hamster model of hypercholesterolaemia. 9th Interna-tional Symposium on Atherosclerosis, Rosemont, USA. (1991): A93.
  • BILLHEIIVIER JT, CROMLEY DA, HIGLEY CA, WEXLER RR,ROBINSON CS, GELLIES PJ: The diarylthiohnidazole, Dup 128, is a potent inhibitor of acyl-CoA:cholesterol acyl-transferase (ACAT). 9th International Symposium on Atherosclerosis, Rosemont, USA. (1991): A94.
  • BILLHEIMER JT, WEXLER RR, GILLIES PJ, RUDEL LL: The effect of Dup 128 on cholesterol absorption and plasma cholesterol in the African green monkey. 11th Interna-tional Symposium on Drugs Affecting Lipid Metabolism, Florence, Italy. (1992): 89.
  • Study on African green monkeys which indicates that Dup 128 inhibits cholesterol absorption and lowers plasma cholesterol.
  • BILLHEIMER JT, WILDE RG: ACAT inhibitors: potentialantihypercholesterolemic agents. Current Patents (1992) Jan: 85.
  • ASHTON MJ, BRIDGE AW, BUSH RC, DRON DI, HARRIS NV, LYTHGOE DJ, RIDDELL D, SMITH S: RP 70676: a potent systemically available inhibitor of acyl-CoA:cholesterol O-acyltransferase. 9th International Symposium on Atherosclerosis, Rosemont, USA. (1991): A100.
  • First disclosure of RP 70676.
  • ASHTON MJ, BRIDGE AW, BUSH RC, DRON DI, HARRIS NV,JONES GD, LYTHGOE DJ, RIDDEL D, SMITH C: RP 70676: a potent systemically available inhibitor of acyl-CoA:cholesterol O-acyltransferase (ACAT). Bioorg. Med. Chem. Lett. (1992) 12 (5):375.
  • ASHTON MJ, BRIDGE AW, BUSH RC, DRON DI, JOANNOU PP, RIDDELL S, ROBERTS S, STEVENSON GVW, WARNE PJ: RP 64477: A potent inhibitor of acyl-CoA:cholesterol O-acyltransferase (ACAT). 9th International Symposium on Atherosclerosis, Rosemont, USA. (1991): A92.
  • First disclosure of RP 64477.
  • PARROTT DP, BRIGHT CP, BURTON B, RIDDELL D, SIMSAFG: RP 64477: a potent inhibitor of ACAT in human cells. 11th International Symposium on Drugs Affecting Lipid Metabolism, Florence, Italy. (1992): 89.
  • KIMURA T, TAKASE Y, HAYASHI K, TANAKA H, OHTSUKA I, SAEKI T, KOGUSHI M, YAMADA T, FUJIMORI T, SAITOU I, AKASAKA K: Structure-activity relationship of N-[2-(di-methylamino)-643-(5-methyl-4-pheny1-1H-imidazol-1 -yilpropozyjphenryli-N'-pentylurea and analogues. Novel potent inhibitors of acyl-CoA:cholesterol O-acyl-transferase with anti-atherosclerotic activity. J. Med. Chem. (1993) 36 (11):1630.
  • Synthesis and SAR of novel ACAT inhibitors.
  • KIMURA T, WATANABE N, MATSUI M, HAYASHI K, TANAKA H, OHTSUKA I, SAEKI T, KOGUSHI M, KO-BAYASHI H, AKASAKA K, YAMAGISHI Y, SAITOU I, YAMATSU I: Structure-activity relationship of a series of phenylureas linked to 4-phenylimidazole. Novel potent Inhibitors of acyl-CoA:cholesterol O-acyltransferase with anti-atherosclerotic activity. 2.J. Med. Chem. (1993) 36(11):1641.
  • Synthesis and SAR of novel ACAT inhibitors.
  • KOGUSHI M, OHTSUKA I, TANAKA H, KIMURA T, HAYASHI K, SAITOU I, YAMATSU I: A potent and novel inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT). 11th International Symposium on Drugs Affecting Lipid Metabolism, Florence, Italy (1992): 88.
  • First disclosure of E5324.
  • TANAKA H, OHTSUKA I, KOGUSHI M, KIMURA T, HAYASHI K, SAEKI T, SAITOU I, YAMATSU I: Effect of anovel ACAT inhibitor (E5324) on the experimental atherosclerosis in rabbits. 11th Inrrzational Symposium on Drugs Affecting Lod Metabolism, Florence, Italy. (1992): 89.
  • The results of this study suggest the direct effect of E5324 in the arterial wall in pre-established hypercholesterolemic rabbits.
  • BELL FP, GAMMELL RB, ST JOHN LC: U-73482: a novelACAT inhibitor that elevates HDL-cholesterol, lowers plasma triglyceride and facilitates hepatic cholesterol mobilization in rat. Atherosclerosis (1992) 92:115.
  • GAMMILL RB, BELL FP, BELL LT, BISAHA SN, WILSON GJ: Anti-atherosclerotic agents. Structurally novel bivalent Inhibitors of acyl-CoA:cholesterol O-acyltransferase with systemic activity. J. Med. Chem. (1990) 33: 2685.
  • First disclosure of U-73482.
  • ARROWSMITH RJ, DANN JG, HARRIS CJ, HONEY AC, O'CONNOR KJ: A potent and novel inhibitor of human ACAT. 9th International Symposium on Atherosclerosis, Rosemont, USA (1991): A185.
  • First disclosure of 447C88.
  • HASSALL DG, ANGELL ADR, GRAHAM A: The effect of anACAT inhibitor 447C88 on foam cell formation in THP-1 macrophages. 11th International Symposium on Drugs Affecting Lipid Metabolism, Florence, Italy. (1992):113.
  • MCCARTHY PA, HAMANAKA ES, MARZETTA CA, BAMBER- GER MJ, GAYNOR BJ, CHANG G, KELLY SE, INSKEEP PB, MAYNE JT, BEYER TA, WALKER FJ, GOLDBERG DI, AMACHER DE, DAVIS KM, DIAZ CL, FREEMAN AM, JOHNSON DA, LACOUR TG, LONG CA, MALONEY ME, MARLINGANO RJ, PETTINI JL, SAND TM, SAVOY LT, WINT LT: CP-113818 and CP-105191 are potent and selective Inhibitors of acyl CoA:cholesterol acyltransferase (ACAT). 11th International Symposium on Drugs Affecting Lipid Metabolism, Florence, Italy. (1992): 113.
  • First disclosure of CP-113818 and CP–105191.
  • MARZETTA CA, SAVOY YE, PETTINI JL, LONG CA, FREE-MAN AM, HAMANAKA ES: The effect of a novel potent ACAT inhibitor (CP-113818) on ACAT activity, choles-terol absorption, liver cholesterol, and plasma lipopro-teins in hamsters, rabbits, and monkeys. 11th International Symposium on Drugs Affecting Lipid Metabo-lism, Florence, Italy. (1992): 113.
  • INSICEEP PB, CONNOLLY AG, DAVIS KM: Pharmacokinet- ics in beagle dogs of CP-105191 and CP-113818, potent Inhibitors of acyl CoA:cholesterol acyltransferase (ACAT). 11th International Symposium on Drugs Affecting Lipid Metabolism, Florence, Italy. (1992): 88.
  • The results of this study indicates that systemic availability in dogs of CP-105191 and CP-113818 after oral administration can be en-hanced by dosing with food.
  • CP-113818, an ACAT inhibitor selected for clinical de-velopment. DN&P (1993) 6(8):618.
  • ADELMAN SJ, MCKEAN ML, ACKERMAN DM, PROZIALECKDH, BERENS MS, FOBARE WF: Hypocholesteroiemic ef-fect of WAY-125147: an inhibitor of both cellular cho-lesterol esterification (ACAT) and low density lipoprotein (IDL) modification. 11th International Sym-posium on Drugs Affecting Lipid Metabolism, Florence, Italy. (1992): 113.
  • FOBARE WF, MCKEAN ML, LEE MC, PROZIALECK DH, CLARK DE, ADELMAN SJ: WAY-125147: a novel inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT) which also inhibits LDL modification. 11th International Sym-posium on Drugs Affecting Lipid Metabolism, Florence, Italy. (1992): 114.
  • First disclosure of WAY-125147.
  • ADELMAN SJ, GUILLOUD R, BANKNEIDER AR, CLARK ML, MCKEAN ML, FOBARE WF: Reduction of plasma lipids in cynomolgous monkeys by WAY-125147: an inhibitor of acyl CoA:cholesterol acyltransferase. FASEB Meeting, New Orleans, USA. (1993): 3239.
  • Study on cynomolgous monkeys which indicate that WAY-125147 lowers plasma total cholesterol.
  • New ACAT inhibitor from Wyeth Ayerst. Drug News (1993) 19: 10.
  • KUSUNOKI J, ARAGANE K, KASE N, IKAWA H, YAMAURA T, SAITO Y: Hyperlipidemic action of F-1394, a newly synthesized ACAT inhibitor. 9th International Symposium on Atherosclerosis, Rosemont, USA. (1991): A90.
  • First disclosure of F-1394.
  • KUSUNOKI J, ARAGANE K, KANESHIGE M, YAMASHITA S, MATSUZAWA Y, YAMAMURA T, OHNISHI H: Effect of a novel acyl Colt:cholesterol acyltransferase inhibitor, F1394, on the lipoproteins in streptozotodn-induced diabetic rats with cholesterol feeding. 66th Scientific Sessions of the American Heart Association, Atlanta, USA. (1993) Abst. (submitted to the Council on Atherosclerosis) p. 65.
  • YAMADA K, OSA S, SHIRAKURA S, OHNISHI E, OHNUMA H, YANASE M, KUMAZAWA T, KUBO K: KF 17828: a novel Inhibitor of acyl-CoA:cholesterol acyltransferase. 11th International Symposium on Drugs Affecting Lipid Metabo-lism, Florence, Italy. (1992): 89.
  • Hypocholesterolemic and anti-atherosclerotic activity of ICF 17828 in cholesterol-fed rabbits.
  • OHISHI E, IMURA R, ODA S, YAMADA K: Effect of KW-3033, a novel ACAT inhibitor, on cholesterol accumula-tion in THP-1 cells. Jpn. J. Pharmacol. (1993) 61 (suppl D: Abst 0–223.
  • MOCHIZUKI T, TANABE H, OTA M, KANOH M, SHIOTA T, ICATAOKA K, TAKEYASU T, TAKESHITA T, MIYAZAKI A, HORIUCHI S: A potent acyl-CoA:cholesterol acyltrans-ferase inhibitor with inhibitory activity toward macro-phage foam cell formation in vitro and anti-hypercholesterolemic effect in vivo. 11th Interna-tional Symposium on Drugs Affecting Lipid Metabolism, Florence, Italy. (1992): 114.
  • First disclosure of TEI-6522.
  • SAICUMA Y, NAGAYOSHI A, HAGIHARA H, NOTSU Y, ONO T: Plasma cholesterol reduction. Effect of F1(129169 in the rat. Jpn.j Pharmacol. (1993) 61 (suppl I): Abst 0–224. First disclosure of FR129169.
  • IWASAWA Y, HATTORI H, NAGATA Y, SHIMIZU A, SAWASAKI Y, KAMEI T: Synthesis and ACAT inhibitory activity of substituted acetamide derivatives. 14th Me-dicinal Chemistry Symposium, Shizuoka, jpn. (1993): P–22.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.