Solute carrier family 18 member B1 (SLC18B1) (SLC18B1)

Solute carrier family 18 member B1 (SLC18B1), also known as the Vesicular Polyamine Transporter (VPAT), is a critical component of the human polyamine transport system (PTS) (Hiasa et al., 2014). It is the human ortholog of the yeast HOL1 protein and belongs to the Major Facilitator Superfamily (MFS) of transporters (UniProt Q6NT16). SLC18B1 functions by sequestering polyamines—essential organic cations like putrescine, spermidine, and spermine—into intracellular vesicles, thereby regulating their cytoplasmic availability and overall cellular homeostasis (Abdulrahman et al., 2021). Because polyamines are vital for cell growth and survival, cancer cells frequently upregulate SLC18B1 and the broader PTS to meet their increased metabolic demands (Casero et al., 2018). This makes SLC18B1 a significant therapeutic target; inhibitors such as AMXT-1501 are currently being evaluated in clinical trials, often in combination with polyamine synthesis inhibitors like eflornithine (DFMO), to starve tumors of these essential nutrients (ClinicalTrials.gov, NCT03538886). Additionally, the transporter's high activity in malignant cells allows it to be exploited for the targeted delivery of polyamine-drug conjugates, which use the PTS as a Trojan horse to internalize cytotoxic agents (Palmer & Wallace, 2010).

Other names

Vesicular polyamine transporterVPATHol1-associated transporterSLC18B1Solute carrier family 18 member B1

Competitive inhibition of polyamine uptake and vesicular sequestration; targeted delivery of polyamine-conjugated cytotoxic agents