From Wikipedia, the free encyclopedia
Mammalian protein found in Homo sapiens
Niemann-Pick C1-Like 1 (NPC1L1) is a
protein found on the
gastrointestinal tract's
epithelial cells
[5] as well as in
hepatocytes .
[6] Specifically, it appears to bind to a critical
mediator of
cholesterol absorption.
The drug
ezetimibe inhibits NPC1L1 causing a reduction in cholesterol
absorption , resulting in a
blood cholesterol reduction of 15-20%.
[7]
Polymorphic variations in NPC1L1
gene could be associated with non-response to ezetimibe treatment.
[8]
NPC1L1 has been shown to be an
accessory receptor for
hepatitis C virus entry into cells, and thus ezetimibe might be used as a therapeutic strategy.
[9]
As
cancer appeared more frequently in patients treated with
simvastatin -
ezetimibe combination therapy in one clinical trial,
[10] it had been
hypothesized that NPC1L1 by ezetimibe might be associated with an increased cancer risk.
[11] However, a
meta-analysis of ezetimibe
clinical data showed no increase in the risk of cancer from treatment with ezetimibe.
[12]
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000015520 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000020447 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, et al. (June 2005).
"The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1)" . Proceedings of the National Academy of Sciences of the United States of America . 102 (23): 8132–7.
Bibcode :
2005PNAS..102.8132G .
doi :
10.1073/pnas.0500269102 .
PMC
1149415 .
PMID
15928087 .
^ Temel RE, Tang W, Ma Y, Rudel LL, Willingham MC, Ioannou YA, Davies JP, Nilsson LM, Yu L (July 2007).
"Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe" . The Journal of Clinical Investigation . 117 (7): 1968–78.
doi :
10.1172/JCI30060 .
PMC
1888567 .
PMID
17571164 .
^ Davis HR, Veltri EP (June 2007).
"Zetia: inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to reduce intestinal cholesterol absorption and treat hyperlipidemia" . Journal of Atherosclerosis and Thrombosis . 14 (3): 99–108.
doi :
10.5551/jat.14.99 .
PMID
17587760 .
^ Universal protein resource accession number
Q9UHC9 for "Niemann-Pick C1-like protein 1 precursor - Homo sapiens (Human)" at
UniProt .
^ Sainz B, Barretto N, Martin DN, Hiraga N, Imamura M, Hussain S, Marsh KA, Yu X, Chayama K, Alrefai WA, Uprichard SL (January 2012).
"Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor" . Nature Medicine . 18 (2): 281–5.
doi :
10.1038/nm.2581 .
PMC
3530957 .
PMID
22231557 .
^ Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, et al. (SEAS Investigators) (September 2008).
"Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis" . The New England Journal of Medicine . 359 (13): 1343–56.
doi :
10.1056/NEJMoa0804602 .
PMID
18765433 .
^ Peto R, Emberson J, Landray M, Baigent C, Collins R, Clare R, Califf R (September 2008).
"Analyses of cancer data from three ezetimibe trials" . The New England Journal of Medicine . 359 (13): 1357–66.
doi :
10.1056/NEJMsa0806603 .
PMID
18765432 .
^ Savarese G, De Ferrari GM, Rosano GM, Perrone-Filardi P (December 2015). "Safety and efficacy of ezetimibe: A meta-analysis". International Journal of Cardiology . 201 : 247–52.
doi :
10.1016/j.ijcard.2015.08.103 .
PMID
26301648 .
External links
Wikimedia Commons has media related to
NPC1L1 .