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SLC transporters: Gateways to treat disease

SLC transporters are the cellular gates that control the movement of hundreds of metabolites, the chemical building blocks and nutrients essential for life.

The solute carrier (SLC) transporter family is the largest group of metabolite transport proteins in the body, accounting for about 2% of known human coding genes.  SLC transporters move metabolites across cell membranes, for the precise control of metabolite levels within cells, tissues and organs for healthy cellular metabolism. Genetic mutations in approximately half of SLC transporters have been linked to either genetically defined diseases (Lin et al. Nat. Rev. Drug Discov. 2015) or complex diseases (Flannick et al. Nat. Genet. 2014), reinforcing the critical importance of this target class and their associated metabolites in disease. Despite this, fewer than 20 of the 450 SLC transporters are targeted by approved drugs — underscoring a massive untapped therapeutic opportunity.

 

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SLC transporters regulate cell- and tissue-specific metabolite levels

SLC transporters gate the movement of hundreds of metabolites to drive cell and organ-specific function. Indeed, an individual metabolite, such as glucose, is regulated by several unique SLC transporters that are differentially expressed by cells in distinct organs, and in doing so ensure the required organ-specific metabolite concentrations.  Jnana is leveraging this specificity by developing therapeutics that selectively target SLC transporters and enable precise disease intervention. Targeting SLC transporters is a powerful mechanism for controlling the movement of metabolites to the right cell in the right organ at the right time to promote healthy cellular metabolism and organ function.

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Metabolites: Mediators of cellular metabolism

Metabolites are chemical building blocks and nutrients essential for life.

Metabolites include amino acids, fats, nucleosides, and sugars as well as metals and ions essential for normal cellular biochemistry and homeostatic regulation. The identity and quantity of metabolites within specific cells is strongly associated with organ-specific function. Organs are highly specialized to synthesize and utilize different metabolites at different levels due to a variety of internal and external cues. As examples, the liver uniquely produces bile acids and urea, the thyroid gland uniquely produces thyroxine, and the heart and brain consume glucose at levels far exceeding any other organ or tissue.

Cellular metabolism is inextricably linked with all other cellular processes and is essential for determining proper cell fate and function. Because of that, dysfunctional metabolism frequently accompanies human disease. This paradigm has led to drug development efforts to address diseases ranging from genetically defined inborn errors of metabolism to cancer and immune-mediated diseases. Metabolite concentration and location is critical to controlling cellular metabolism.

The movement of metabolites into and out of cells and organelles is regulated by distinct SLC transporters whose expression is often cell-specific and related to disease state. At Jnana, we are dedicated to developing new therapeutics that target SLC transporters with demonstrated links to human disease.

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