P-glycoprotein is an important transporter belonging to ATP-Binding Cassette pumps (ABC-B1). This transporter plays a fundamental role in several degenerative diseases such as Alzheimer's, Parkinson's and other forms of dementia, as well as in tumors. This transporter is localized at the blood brain barrier (BBB) where it is involved in the efflux of endogenous and exogenous compounds and it is overexpressed in several tumor cell lines determining Multi Drug Resistance (MDR). In this chapter, we will examine the in vitro biological assays useful to establish the P-gp interactive mechanisms of a ligand and its potential in terms of therapy and diagnosis. In addition, examples of Structure Activity Relationship (SAR) studies of P-gp modulators will be described. Moreover, P-gp imaging by PET with different radioligands (11C and 18F -radiolabelled) will be herein discussed. Finally, the difficulty in the definition of a pharmacophore for the design of substrates, modulators and inhibitors is also critically approached in this chapter.
P-Glycoprotein, a biological and medicinal chemistry/radiochemistry point of view
Abate C.
;Colabufo N. A.
;Contino M.
2021-01-01
Abstract
P-glycoprotein is an important transporter belonging to ATP-Binding Cassette pumps (ABC-B1). This transporter plays a fundamental role in several degenerative diseases such as Alzheimer's, Parkinson's and other forms of dementia, as well as in tumors. This transporter is localized at the blood brain barrier (BBB) where it is involved in the efflux of endogenous and exogenous compounds and it is overexpressed in several tumor cell lines determining Multi Drug Resistance (MDR). In this chapter, we will examine the in vitro biological assays useful to establish the P-gp interactive mechanisms of a ligand and its potential in terms of therapy and diagnosis. In addition, examples of Structure Activity Relationship (SAR) studies of P-gp modulators will be described. Moreover, P-gp imaging by PET with different radioligands (11C and 18F -radiolabelled) will be herein discussed. Finally, the difficulty in the definition of a pharmacophore for the design of substrates, modulators and inhibitors is also critically approached in this chapter.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
