There are studies indicating that quercetin is not a potent OCT1 inhibitor (Mandery et al., 2012; Glaeser et al., 2014). activity may also be of great significance to the maintenance of homeostasis in the body (Nies et al., 2011b; Lozano et al., 2013; Brosseau and Ramotar, 2019; Li et al., 2019). Herein the physiological and pharmacological effects of OCT1 are briefly introduced, followed by a focused review on DDIs mediated by OCT1. 2 Molecular PDK1 inhibitor Cloning and Characterization of Organic Cation Transporter 1 OCT1 is usually a member of the Solute Carrier (SLC) Family 22 responsible for the uptake of numerous organic cations, anions and zwitterions, across the plasma membrane (Koepsell, 2013). PDK1 inhibitor Rat OCT1 (rOCT1) was the first cloned member of the SLC22A family. rOCT1 was cloned in 1994, and hOCT1 in 1997 by Koepsell group (Grundemann et al., 1994; Gorboulev et al., 1997). The human gene encoding hOCT1 is located on chromosome 6q26 and consists of 11 exons and 10 introns (Koehler et al., 1997). The human OCT1 protein has 554 amino acids. Like most transporters in the SLC22A family, it is composed of 12 -helical transmembrane domains (TMDs) with intracellular N- and C-termini (Shu et al., 2003; Koepsell, 2013; Lozano et al., 2013). There is a large glycosylated extracellular loop between the TMD 1 and TMD 2, which can form disulfide PDK1 inhibitor bonds for protein oligomerization. In addition, between the TMD 6 and TMD 7, there is an intracellular loop with consensus sites that can be phosphorylated by several protein kinases. These glycosylation and phosphorylation sites are associated with the regulation of transport functions by regulatory proteins such as protein kinases A&C (Ciarimboli and Schlatter, 2005; Shu, 2011; Brosseau and Ramotar, 2019). 3 Distribution and Function of Organic Cation Transporter 1 in Human Tissues The importance of hOCT1 in drug disposition and response is usually implicated by its tissue expression pattern and cellular location. Although hOCT1 is usually widely distributed in human tissues, it is primarily expressed in the liver (Koepsell et al., 2003) (Physique 1). In hepatocytes, it has been located at the sinusoidal (basolateral) membrane. Of note, it is less expressed in cholangiocytes as compared to hepatocytes in the liver (Nies et al., 2009). In the intestine, there is evidence from immunolocalization and pharmacokinetics (PK) studies in support of hOCT1 expression in the basolateral membrane (Muller et al., 2005). However, this PDK1 inhibitor has been challenged by other results which supported that hOCT1 and mouse OCT1 (mOCT1) were actually expressed in the apical membrane of intestinal epithelia cells (Han et al., 2013). Further investigation is needed to settle this dispute. In the kidney, while rOCT1 has been reported to be located to the basolateral membrane of epithelial cells in the proximal tubules (Karbach et al., 2000; Sugawara-Yokoo et al., 2000), there is immunohistochemistry evidence supporting the location of hOCT1 in the apical membranes of proximal and distal tubules (Tzvetkov et al., 2009). In the lung, OCT1 is located in the lumen (apical) membrane of ciliated cells (Lips et al., 2005) and bronchial epithelial cells (Mukherjee et al., 2012). In addition, OCT1 has been reported to be expressed around the luminal side of brain microvessel endothelial cells (BMECs) (Lin et al., 2010), olfactory and nasal respiratory tissues (Chemuturi and Donovan, 2007), ovary, prostate, testis (Jung et al., 2008), cardiomyocytes (Rossato et al., 2011) and CD4+ cells of HIV-infected patients (Minuesa et al., 2008; Jung et al., 2013). Open in a separate window PDK1 inhibitor Physique 1 The Mst1 transcript levels of gene in major human tissues. The RNA sequencing data for human tissues were retrieved from https://www.ncbi.nlm.nih.gov/gene/6580. RPKM stands for the Reads Per kilobase of transcript, per Million mapped reads in RNA sequencing, which is a normalized unit of transcript expression. OCT1 is usually a poly-specific amphiphilic solute facilitator of.