BIOMAT Database Logo BIOMAT Database Logo

Intestinal absorption mechanisms of 2'-deoxy-2'-β-fluoro-4'-azidocytidine, a cytidine analog for AIDS treatment, and its interaction with P-glycoprotein, multidrug resistance-associated protein 2 and breast cancer resistance protein. 2017

Yixian Liu, and Bingjie Liu, and Yan Zhang, and Youmei Peng, and Chenzheng Huang, and Ning Wang, and Jinhua Jiang, and Qingduan Wang, and Junbiao Chang
Henan Key Laboratory for Pharmacology of Liver, Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, China; School of Pharmaceutical Science, Zhengzhou University, Zhengzhou 450001, China.

2'-Deoxy-2'-β-fluoro-4'-azidocytidine (FNC), a cytidine analog, has attracted great interest because of its potent activity against wild-type and multidrug-resistant HIV. The purpose of current study was to investigate the absorption mechanisms of FNC in the small intestine, as well as the interactions between FNC and P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). The experiments were performed using Caco-2 cells and the rat small intestine. The uptake experiment indicated that FNC concentration, extracellular pH and the incubated temperature could influence the uptake of FNC in Caco-2 cells. NaN3, verapamil, probenecid, MK571 and GF120918 could significantly increase the FNC uptake in Caco-2 cells. The transport experiment showed that both the absorption and secretion of FNC were concentration dependent. The secretion of FNC was approximately 2-fold greater than the absorption. In the presence of verapamil, probenecid, MK571 or GF120918, the efflux ratio decreased by >50%. In everted rat intestine, the absorption of FNC also depended on its concentration and was not significantly different in the different segments of the small intestine. Real-time RT-PCR results indicated that the gene expressions of P-gp, MRP2 and BCRP were up-regulated after exposure to FNC. The reduction in accumulation of rhodamine 123 after treatment with FNC revealed its ability to up-regulate P-gp activity. In conclusion, FNC was completely absorbed by passive diffusion and active transport mechanisms. P-gp, MRP2 and BCRP could influence the absorption of FNC in the small intestine. FNC could modulate the gene expressions of P-gp, MRP2 and BCRP, and increase the activity of P-gp.

UI MeSH Term Description Entries
D007408 Intestinal Absorption Uptake of substances through the lining of the INTESTINES. Absorption, Intestinal
D007421 Intestine, Small The portion of the GASTROINTESTINAL TRACT between the PYLORUS of the STOMACH and the ILEOCECAL VALVE of the LARGE INTESTINE. It is divisible into three portions: the DUODENUM, the JEJUNUM, and the ILEUM. Small Intestine,Intestines, Small,Small Intestines
D008297 Male Males
D009363 Neoplasm Proteins Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm. Proteins, Neoplasm
D003841 Deoxycytidine A nucleoside component of DNA composed of CYTOSINE and DEOXYRIBOSE. Cytosine Deoxyribonucleoside,Cytosine Deoxyriboside,Deoxyribonucleoside, Cytosine,Deoxyriboside, Cytosine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000070997 ATP Binding Cassette Transporter, Subfamily G, Member 2 ATP-binding cassette transporter, sub-family G protein that functions as a high capacity UREA exporter, transporter of STEROLS, and in the absorption and efflux of many drugs. Its efflux activity for ANTINEOPLASTIC AGENTS contributes to DRUG RESISTANCE. It functions as a homodimer and is expressed by cells in a variety of organs, as well as by NEOPLASTIC STEM CELLS. ABCG2 Protein,ABCG2 Transporter,ATP Binding Cassette Transporter, Sub-Family G, Member 2,CD338 Antigen
D000089762 Multidrug Resistance-Associated Protein 2 An ATP-BINDING CASSETTE TRANSPORTERS subfamily protein that is localized on the canalicular membrane of HEPATOCYTES, as well as on the apical membrane of EPITHELIAL CELLS of the DUODENUM, JEJUNUM and PROXIMAL RENAL TUBULE. ABCC2 Protein,CMOAT,CMOAT Protein,CMOAT Transport Protein,Canalicular Multispecific Organic Anion Transporter,MRP2 Protein, Multidrug Resistance,MRP2 Transport Protein,Multidrug Resistance Protein MRP2,Multidrug-Resistance Associated Protein 2,Multidrug Resistance Associated Protein 2,Transport Protein, CMOAT,Transport Protein, MRP2
D000163 Acquired Immunodeficiency Syndrome An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. AIDS,Immunodeficiency Syndrome, Acquired,Immunologic Deficiency Syndrome, Acquired,Acquired Immune Deficiency Syndrome,Acquired Immuno-Deficiency Syndrome,Acquired Immuno Deficiency Syndrome,Acquired Immuno-Deficiency Syndromes,Acquired Immunodeficiency Syndromes,Immuno-Deficiency Syndrome, Acquired,Immuno-Deficiency Syndromes, Acquired,Immunodeficiency Syndromes, Acquired,Syndrome, Acquired Immuno-Deficiency,Syndrome, Acquired Immunodeficiency,Syndromes, Acquired Immuno-Deficiency,Syndromes, Acquired Immunodeficiency
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

Related Publications

Yixian Liu, and Bingjie Liu, and Yan Zhang, and Youmei Peng, and Chenzheng Huang, and Ning Wang, and Jinhua Jiang, and Qingduan Wang, and Junbiao Chang
Antiviral activity of FNC, 2'-deoxy-2'-β-fluoro-4'-azidocytidine, against human and duck HBV replication.
January 2012, Antiviral therapy,
Yixian Liu, and Bingjie Liu, and Yan Zhang, and Youmei Peng, and Chenzheng Huang, and Ning Wang, and Jinhua Jiang, and Qingduan Wang, and Junbiao Chang
Binding Site Interactions of Modulators of Breast Cancer Resistance Protein, Multidrug Resistance-Associated Protein 2, and P-Glycoprotein Activity.
July 2020, Molecular pharmaceutics,
Yixian Liu, and Bingjie Liu, and Yan Zhang, and Youmei Peng, and Chenzheng Huang, and Ning Wang, and Jinhua Jiang, and Qingduan Wang, and Junbiao Chang
Effect of GenX on P-Glycoprotein, Breast Cancer Resistance Protein, and Multidrug Resistance-Associated Protein 2 at the Blood-Brain Barrier.
March 2020, Environmental health perspectives,
Yixian Liu, and Bingjie Liu, and Yan Zhang, and Youmei Peng, and Chenzheng Huang, and Ning Wang, and Jinhua Jiang, and Qingduan Wang, and Junbiao Chang
Safety Assessment of a Nucleoside Analogue FNC (2'-deoxy-2'- β-fluoro-4'-azidocytidine ) in Balb/c Mice: Acute Toxicity Study.
June 2023, Asian Pacific journal of cancer prevention : APJCP,
Yixian Liu, and Bingjie Liu, and Yan Zhang, and Youmei Peng, and Chenzheng Huang, and Ning Wang, and Jinhua Jiang, and Qingduan Wang, and Junbiao Chang
Closing the gaps: a full scan of the intestinal expression of p-glycoprotein, breast cancer resistance protein, and multidrug resistance-associated protein 2 in male and female rats.
July 2008, Drug metabolism and disposition: the biological fate of chemicals,
Yixian Liu, and Bingjie Liu, and Yan Zhang, and Youmei Peng, and Chenzheng Huang, and Ning Wang, and Jinhua Jiang, and Qingduan Wang, and Junbiao Chang
Mechanistic Insight into Antiretroviral Potency of 2'-Deoxy-2'-β-fluoro-4'-azidocytidine (FNC) with a Long-Lasting Effect on HIV-1 Prevention.
August 2020, Journal of medicinal chemistry,
Yixian Liu, and Bingjie Liu, and Yan Zhang, and Youmei Peng, and Chenzheng Huang, and Ning Wang, and Jinhua Jiang, and Qingduan Wang, and Junbiao Chang
P-glycoprotein, multidrug-resistance-associated protein and Parkinson's disease.
January 2001, European neurology,
Yixian Liu, and Bingjie Liu, and Yan Zhang, and Youmei Peng, and Chenzheng Huang, and Ning Wang, and Jinhua Jiang, and Qingduan Wang, and Junbiao Chang
Imaging multidrug resistance with radiolabeled substrates for P-glycoprotein and multidrug resistance protein.
February 2001, Cancer biotherapy & radiopharmaceuticals,
Yixian Liu, and Bingjie Liu, and Yan Zhang, and Youmei Peng, and Chenzheng Huang, and Ning Wang, and Jinhua Jiang, and Qingduan Wang, and Junbiao Chang
The 4'-O-benzylated doxorubicin analog WP744 overcomes resistance mediated by P-glycoprotein, multidrug resistance protein and breast cancer resistance protein in cell lines and acute myeloid leukemia cells.
April 2007, Investigational new drugs,
Yixian Liu, and Bingjie Liu, and Yan Zhang, and Youmei Peng, and Chenzheng Huang, and Ning Wang, and Jinhua Jiang, and Qingduan Wang, and Junbiao Chang
Histopathological assessment of multidrug resistance in gastric cancer: expression of P-glycoprotein, multidrug resistance-associated protein, and lung-resistance protein.
January 1999, Surgery today,
Copied contents to your clipboard!