H R Davis

Summary

Affiliation: Schering-Plough Research Institute
Country: USA

Publications

  1. ncbi request reprint Zetia: inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to reduce intestinal cholesterol absorption and treat hyperlipidemia
    Harry R Davis
    Department of Cardiovascular Metabolic Disease Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    J Atheroscler Thromb 14:99-108. 2007
  2. ncbi request reprint Niemann-Pick C1 Like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis
    Harry R Davis
    Department of Cardiovascular Metabolic Disease and Department of Discovery Technologies, Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
    J Biol Chem 279:33586-92. 2004
  3. doi request reprint Niemann-Pick C1 Like 1 (NPC1L1) an intestinal sterol transporter
    Harry R Davis
    Department of Cardiovascular Metabolic Disease, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Biochim Biophys Acta 1791:679-83. 2009
  4. ncbi request reprint Ezetimibe, a potent cholesterol absorption inhibitor, inhibits the development of atherosclerosis in ApoE knockout mice
    H R Davis
    Department of Central Nervous System and Cardiovascular Research, Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Arterioscler Thromb Vasc Biol 21:2032-8. 2001
  5. doi request reprint Cholesterol homeostasis by the intestine: lessons from Niemann-Pick C1 Like 1 [NPC1L1)
    Harry R Davis
    Department of Cardiovascular Metabolic Disease, Schering Plough Research Institute, K15 2 2600, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Atheroscler Suppl 9:77-81. 2008
  6. ncbi request reprint Deficiency of Niemann-Pick C1 Like 1 prevents atherosclerosis in ApoE-/- mice
    Harry R Davis
    Department of Cardiovascular Metabolic Disease, Schering Plough Research Institute, K15 2 2600, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Arterioscler Thromb Vasc Biol 27:841-9. 2007
  7. pmc Comparison of the activity and disposition of the novel cholesterol absorption inhibitor, SCH58235, and its glucuronide, SCH60663
    M van Heek
    CNS CV Pharmacology, Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
    Br J Pharmacol 129:1748-54. 2000
  8. pmc Diet-induced obese mice develop peripheral, but not central, resistance to leptin
    M van Heek
    Department of CNS and Cardiovascular Research, Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
    J Clin Invest 99:385-90. 1997
  9. ncbi request reprint Ezetimibe, a potent cholesterol absorption inhibitor, normalizes combined dyslipidemia in obese hyperinsulinemic hamsters
    M van Heek
    CNS CV Biological Research, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Diabetes 50:1330-5. 2001
  10. pmc Ezetimibe selectively inhibits intestinal cholesterol absorption in rodents in the presence and absence of exocrine pancreatic function
    M van Heek
    CNS CV Pharmacology, Schering Plough Research Institute, Kenilworth, New Jersey, NJ 07033, USA
    Br J Pharmacol 134:409-17. 2001

Collaborators

Detail Information

Publications25

  1. ncbi request reprint Zetia: inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to reduce intestinal cholesterol absorption and treat hyperlipidemia
    Harry R Davis
    Department of Cardiovascular Metabolic Disease Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    J Atheroscler Thromb 14:99-108. 2007
    ..Ezetimibe in combination with statins produces additional reductions in plasma cholesterol levels and allows for more patients to achieve their LDL-C goals...
  2. ncbi request reprint Niemann-Pick C1 Like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis
    Harry R Davis
    Department of Cardiovascular Metabolic Disease and Department of Discovery Technologies, Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
    J Biol Chem 279:33586-92. 2004
    ..NPC1L1 is required for intestinal uptake of both cholesterol and phytosterols and plays a major role in cholesterol homeostasis. Thus, NPC1L1 may be a useful drug target for the treatment of hypercholesterolemia and sitosterolemia...
  3. doi request reprint Niemann-Pick C1 Like 1 (NPC1L1) an intestinal sterol transporter
    Harry R Davis
    Department of Cardiovascular Metabolic Disease, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Biochim Biophys Acta 1791:679-83. 2009
    ..Therefore, NPC1L1 is a critical intestinal sterol uptake transporter which influences whole body cholesterol homeostasis...
  4. ncbi request reprint Ezetimibe, a potent cholesterol absorption inhibitor, inhibits the development of atherosclerosis in ApoE knockout mice
    H R Davis
    Department of Central Nervous System and Cardiovascular Research, Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Arterioscler Thromb Vasc Biol 21:2032-8. 2001
    ....
  5. doi request reprint Cholesterol homeostasis by the intestine: lessons from Niemann-Pick C1 Like 1 [NPC1L1)
    Harry R Davis
    Department of Cardiovascular Metabolic Disease, Schering Plough Research Institute, K15 2 2600, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Atheroscler Suppl 9:77-81. 2008
    ..Therefore, NPC1L1 is the critical intestinal sterol transporter which influences whole body cholesterol homeostasis, and is the molecular target of ezetimibe...
  6. ncbi request reprint Deficiency of Niemann-Pick C1 Like 1 prevents atherosclerosis in ApoE-/- mice
    Harry R Davis
    Department of Cardiovascular Metabolic Disease, Schering Plough Research Institute, K15 2 2600, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Arterioscler Thromb Vasc Biol 27:841-9. 2007
    ..The objective of this study was to determine whether the deficiency of Niemann-Pick C1 Like 1 (Npc1l1) prevents atherosclerosis in apoE null mice...
  7. pmc Comparison of the activity and disposition of the novel cholesterol absorption inhibitor, SCH58235, and its glucuronide, SCH60663
    M van Heek
    CNS CV Pharmacology, Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
    Br J Pharmacol 129:1748-54. 2000
    ..Taken together, these data may explain the potency of SCH58235 in the rat (ID(50) = 0.0015 mg kg(-1)) and rhesus monkey (ID(50) = 0.0005 mg kg(-1))...
  8. pmc Diet-induced obese mice develop peripheral, but not central, resistance to leptin
    M van Heek
    Department of CNS and Cardiovascular Research, Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
    J Clin Invest 99:385-90. 1997
    ..These data demonstrate that, in a diet-induced obesity model, mice exhibit resistance to peripherally administered leptin, while retaining sensitivity to centrally administered leptin...
  9. ncbi request reprint Ezetimibe, a potent cholesterol absorption inhibitor, normalizes combined dyslipidemia in obese hyperinsulinemic hamsters
    M van Heek
    CNS CV Biological Research, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Diabetes 50:1330-5. 2001
    ....
  10. pmc Ezetimibe selectively inhibits intestinal cholesterol absorption in rodents in the presence and absence of exocrine pancreatic function
    M van Heek
    CNS CV Pharmacology, Schering Plough Research Institute, Kenilworth, New Jersey, NJ 07033, USA
    Br J Pharmacol 134:409-17. 2001
    ..Ezetimibe does not affect the absorption of triglyceride as a pancreatic lipase inhibitor (Orlistat) would, nor does it affect the absorption of vitamin A, D or taurocholate, as a bile acid sequestrant (cholestyramine) would...
  11. ncbi request reprint The cholesterol absorption inhibitor, ezetimibe, decreases diet-induced hypercholesterolemia in monkeys
    M van Heek
    CNS CV Biological Research, Schering Plough Research Institute, K15 2 2600, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA
    Eur J Pharmacol 415:79-84. 2001
    ..These data indicate that these cholesterol absorption inhibitors reduce cholesterol content in chylomicrons, which indirectly leads to a decrease in LDL cholesterol and particle number...
  12. ncbi request reprint The synergistic hypocholesterolemic activity of the potent cholesterol absorption inhibitor, ezetimibe, in combination with 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors in dogs
    H R Davis
    Department of CNS and Cardiovascular Research, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA
    Metabolism 50:1234-41. 2001
    ..The combination of this class of cholesterol absorption inhibitors with an HMG CoA reductase inhibitor should be very effective clinically at reducing plasma cholesterol levels, even with reduced dietary intake of cholesterol...
  13. ncbi request reprint Discovery of 1-(4-fluorophenyl)-(3R)-[3-(4-fluorophenyl)-(3S)-hydroxypropyl]-(4S)-(4 -hydroxyphenyl)-2-azetidinone (SCH 58235): a designed, potent, orally active inhibitor of cholesterol absorption
    S B Rosenblum
    Department of Discovery Research, Schering Plough Research Institute, Kenilworth, New Jersey 07033 0539, USA
    J Med Chem 41:973-80. 1998
    ..04 mg/kg/day for the reduction of liver cholesteryl esters in a 7-day cholesterol-fed hamster model...
  14. doi request reprint An assessment of the carcinogenic potential of ezetimibe using nonclinical data in a weight-of-evidence approach
    M Halleck
    Schering Plough Research Institute Lafayette, NJ, USA
    Toxicology 258:116-30. 2009
    ....
  15. ncbi request reprint The relationship of tissue localization, distribution and turnover to feeding after intraperitoneal 125I-leptin administration to ob/ob and db/db mice
    M van Heek
    Department of CNS and Cardiovascular Pharmacology, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA
    Horm Metab Res 28:653-8. 1996
    ....
  16. ncbi request reprint Synthesis of iodinated biochemical tools related to the 2-azetidinone class of cholesterol absorption inhibitors
    Duane A Burnett
    Schering Plough Research Institute, 2015 Galloping Hill Road MS 2800, Kenilworth, NJ 07033 0539, USA
    Bioorg Med Chem Lett 12:311-4. 2002
    ..They are structurally consistent with the allowable SAR of the 2-azetidinone class of cholesterol absorption inhibitors...
  17. ncbi request reprint Simvastatin with or without ezetimibe in familial hypercholesterolemia
    Harry R Davis
    N Engl J Med 359:531; author reply 532-3. 2008
  18. ncbi request reprint Synthesis of fluorescent biochemical tools related to the 2-azetidinone class of cholesterol absorption inhibitors
    Duane A Burnett
    Schering Plough Research Institute, 2015 Galloping Hill Road MS 2800, Kenilworth, NJ 07033 0539, USA
    Bioorg Med Chem Lett 12:315-8. 2002
    ..Biological testing reveals that they are potent CAIs and are suitable tools for the investigation of the azetidinone CAI mechanism of action (MOA)...
  19. ncbi request reprint The identification of intestinal scavenger receptor class B, type I (SR-BI) by expression cloning and its role in cholesterol absorption
    Scott W Altmann
    Department of CNS and Cardiovascular Research, Schering Plough Research Institute, Kenilworth, NJ 07033 0539, USA
    Biochim Biophys Acta 1580:77-93. 2002
    ..In contrast studies with SR-B1 knockout mice suggest that SR-B1 is not essential for intestinal cholesterol absorption or the activity of ezetimibe...
  20. ncbi request reprint Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption
    Scott W Altmann
    Department of Cardiovascular Endocrine Research, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ, 07033 0539, USA
    Science 303:1201-4. 2004
    ..Ezetimibe, a drug that inhibits cholesterol absorption, had no effect in NPC1L1 knockout mice, suggesting that NPC1L1 resides in an ezetimibe-sensitive pathway responsible for intestinal cholesterol absorption...
  21. ncbi request reprint In vivo responsiveness to ezetimibe correlates with niemann-pick C1 like-1 (NPC1L1) binding affinity: Comparison of multiple species NPC1L1 orthologs
    Brian E Hawes
    Department of Cardiovascular Metabolic Disease, Schering Plough Research Institute, Kenilworth, New Jersey, USA
    Mol Pharmacol 71:19-29. 2007
    ..The results demonstrate that the ability of compounds to bind to NPC1L1 is the major determinant of in vivo responsiveness...
  22. pmc Targeted deletion of Gpbar1 protects mice from cholesterol gallstone formation
    Galya Vassileva
    Department of Discovery Technologies, Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Biochem J 398:423-30. 2006
    ..These results suggest that Gpbar1 plays a critical role in the formation of gallstones, possibly via a regulatory mechanism involving the cholesterol 7alpha-hydroxylase pathway...
  23. pmc The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1)
    Margarita Garcia-Calvo
    Department of Metabolic Disorders, Merck Research Laboratories, Rahway, NJ 07065, USA
    Proc Natl Acad Sci U S A 102:8132-7. 2005
    ..These results unequivocally establish NPC1L1 as the direct target of ezetimibe and should facilitate efforts to identify the molecular mechanism of cholesterol transport...
  24. ncbi request reprint Characterization of the putative native and recombinant rat sterol transporter Niemann-Pick C1 Like 1 (NPC1L1) protein
    Sai Prasad N Iyer
    Department of Cardiovascular Metabolic Disease, Schering Plough Research Institute, 2015 Galloping Hill Rd, K15 3 3600, Kenilworth, NJ 07033, USA
    Biochim Biophys Acta 1722:282-92. 2005
    ..These biochemical data indicate that NPC1L1 exists as a predominantly cell surface membrane expressed protein, consistent with its proposed role as the putative intestinal sterol transporter...
  25. pmc Ezetimibe potently inhibits cholesterol absorption but does not affect acute hepatic or intestinal cholesterol synthesis in rats
    Margaret van Heek
    Cardiovascular Endocrine Biology, Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Br J Pharmacol 138:1459-64. 2003
    ....