2.B.118.  The Click-Tambjamine Anionophore Carrier (CTAC) Family 

An excessive production of lactate by cancer cells fosters tumor growth and metastasis. Therefore, targeting lactate metabolism and transport offers a  therapeutic strategy against cancer, based on a dependency of some cancer cells for lactate as energy fuel or as an oncogenic signal. Alonso-Carrillo et al. 2023 presented a family of anionophores based on the structures of click-tambjamines that have proven to be active lactate carriers across phospholipid membranes. Compound 1, the most potent lactate transmembrane carrier, was studied in HeLa cells. The use of a monocarboxylate transporters (MCTs) inhibitor proved that 1 is an active lactate transporter in living cells, confirming the results obtained in phospholipid vesicles. An additive effect of compound 1 with cisplatin was observed in HeLa cells. Identification of active lactate anionophores working in living cells opens up ways to exploit this class of compounds as molecular tools and drugs addressing dysregulated lactate metabolism (Alonso-Carrillo et al. 2023).



Alonso-Carrillo, D., A. Arias-Betancur, I. Carreira-Barral, P. Fontova, V. Soto-Cerrato, M. García-Valverde, R. Pérez-Tomás, and R. Quesada. (2023). Small molecule anion carriers facilitate lactate transport in model liposomes and cells. iScience 26: 107898.