Science

Translation, interrupted.

Fig. 01 · Premature stop codon halts translation — mRNA threads 5′→3′ through fixed ribosome
5′ 3′ AUG GCU CGA UAA premature stop · UAA translation halts truncated peptide released
Mechanism UAA, UAG, or UGA codon appears mid-gene, before the natural stop.
Consequence Loss of function — often in a structural or regulatory protein essential to organ integrity.
Therapeutic gap No approved targeted therapy. Current care is symptomatic or organ-replacement.
Mechanism of Action

How exaluren works

Exaluren promotes premature termination codon (PTC) readthrough via selective ribosome modulation, partially restoring full-length protein production.

01

Nonsense mutation creates a premature stop codon (PTC)

A single nucleotide substitution converts an amino acid codon into a premature stop codon (PTC). Protein translation terminates early, producing a non-functional protein fragment — the root cause in NMAS, NM-ADPKD, and other nonsense mutation conditions.

02

Exaluren selectively modulates the human ribosome

Exaluren binds to the small (40S) subunit of the eukaryotic ribosome, reducing discrimination at the PTC — allowing a near-cognate aminoacyl-tRNA to insert and translation to continue.

03

Full-length functional protein restored

Translation completes, producing a full-length protein. Gene-agnostic mechanism: the same compound addresses nonsense mutations across COL4A3, COL4A4, COL4A5 (Alport) and PKD1/PKD2 (ADPKD).

04

Designed for selectivity and long-term administration

Administered subcutaneously. Markedly reduced affinity for mitochondrial and bacterial ribosomes versus aminoglycoside antibiotics. Concentrates in kidney cells via megalin-mediated uptake.

Compound Profile

Designed for selectivity and kidney concentration

Human Ribosome Selectivity

Markedly reduced affinity for mitochondrial and bacterial ribosomes — designed to avoid the ototoxicity and nephrotoxicity associated with aminoglycoside antibiotics at therapeutic doses.

Kidney-Concentrated Delivery

Administered subcutaneously and transported into cells via megalin — a receptor highly expressed in kidney and epithelial tissues — supporting preferential accumulation in kidney cells.

Gene-Agnostic Platform

Targets the premature stop codon, not the gene — enabling investigation across multiple rare diseases caused by nonsense mutations from a single compound.

Peer-reviewed

The science is in the literature.

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