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P‐glycoprotein ‐ an ABC Transporter: Toxin Removal to Chemotherapy Interference (LB109)
Author(s) -
Adamson Bennett,
Pham Tiffany,
Kronenfeld Jason,
Reilly Bianca,
Crowther Meghan,
Fraijo Savanah,
Cherrington Emily,
Futch Liane,
Cherrington Nathan
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb109
Subject(s) - atp binding cassette transporter , transporter , p glycoprotein , drug , pharmacology , chemistry , binding site , prodrug , cancer research , biochemistry , medicine , multiple drug resistance , gene , antibiotics
Cancer claimed 7.6 million lives worldwide in 2013. Despite improvements in chemotherapy, most relapsed cancers become drug resistant due to an ATP‐binding cassette transporter, P‐glycoprotein (P‐gp). P‐gp is a gatekeeper in multiple tissues, controlling exposure to drugs and toxins by pumping them out of the cell. This homodimeric protein of 1,280 amino acids is located on the apical surface and extrudes lipid soluble molecules. Pharmaceutical companies must determine if their drugs are P‐gp substrates before proceeding to clinical trials, as the amount of drug entering the body may vary widely due to P‐gp function. P‐gp may reduce the amount of drugs reaching circulation by transporting drugs back into the digestive tract lumen. Many chemicals act as modulators of P‐gp’s function; for example, the flavonoid naringin in grapefruit juice interacts with P‐gp and may significantly increase the uptake of some statin drugs. The active sites and conformational changes of P‐gp have not been elucidated, as it has been difficult to crystallize P‐gp with its substrates. P‐gp’s complex structure and multiple binding sites allow for interaction with many drug molecules, which enter P‐gp’s binding pocket via pairs of alpha‐helices on opposite sides of P‐gp. The Ironwood Ridge High School SMART team (Students Modeling A Research Topic) modeled P‐gp using 3D printing technology. Grant Funding Source : Supported by a grant from NIH‐SEPA and NIH‐CTSA.