All four compounds successfully rescued p53 expression in H1299 R213X cells, outperforming Ataluren and matching G418 at significantly lower concentrations. The restored p53 exhibited nuclear localization upon genotoxic stress and induced transcription of canonical targets. These findings highlight the therapeutic potential of these compounds for treating TP53 nonsense mutations in cancer and lay the groundwork for the development of targeted nonsense mutation-specific treatment for a wide range of pathologies, including new emergent p53 related diseases.

P1/2, N=3, Not yet recruiting, Biomarin Pharmaceutical Inc.

P3, N=270, Completed, PTC Therapeutics | Enrolling by invitation --> Completed | Trial completion date: Apr 2025 --> Feb 2026 | Trial primary completion date: Apr 2025 --> Feb 2026

P2, N=175, Enrolling by invitation, Wave Life Sciences Ltd. | Not yet recruiting --> Enrolling by invitation

P=N/A, N=316, Completed, PTC Therapeutics | Active, not recruiting --> Completed

P3, N=80, Recruiting, Solid Biosciences Inc. | Not yet recruiting --> Recruiting

P1/2, N=60, Recruiting, Solid Biosciences Inc. | N=40 --> 60

P=N/A, N=0, Available, Avidity Biosciences, Inc.

Interestingly, AMPD3 can be an effective therapeutic target for NF1-associated diseases. Together, our study suggests that ataluren can be considered a therapeutic agent for some NF1NS/+ patients and contributes to expanding insights into NF1 therapy.

P3, N=228, Completed, Sarepta Therapeutics, Inc. | Active, not recruiting --> Completed

P2, N=10, Terminated, Pfizer | Active, not recruiting --> Terminated; All participants who have received fordadistrogene movaparvovec in any Pfizer study will now be assessed for long-term safety in one combined study: C3391003

P3, N=7, Terminated, Pfizer | Active, not recruiting --> Terminated; All participants who have received fordadistrogene movaparvovec in any Pfizer study will now be assessed for long-term safety in 1 combined study: C3391003