Adenylosuccinic Acid Is a Non-Toxic Small Molecule In Vitro and In Vivo
Adenylosuccinic acid (ASA) is a small molecule dicarboxylate that could be a strong clinical development candidate for inherited myopathies involving dysregulated purine nucleotide metabolism. Currently, there are no published pharmacokinetic/dynamic or toxicology data available, although 10-year cl...
| Published in: | Pharmaceuticals |
|---|---|
| Main Authors: | , , |
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-10-01
|
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/16/10/1458 |
| _version_ | 1851875397137858560 |
|---|---|
| author | Cara A. Timpani Lorna Rasmussen Emma Rybalka |
| author_facet | Cara A. Timpani Lorna Rasmussen Emma Rybalka |
| author_sort | Cara A. Timpani |
| collection | DOAJ |
| container_title | Pharmaceuticals |
| description | Adenylosuccinic acid (ASA) is a small molecule dicarboxylate that could be a strong clinical development candidate for inherited myopathies involving dysregulated purine nucleotide metabolism. Currently, there are no published pharmacokinetic/dynamic or toxicology data available, although 10-year clinical trial data on Duchenne muscular dystrophy patients suggests it is a chronically safe drug. In this study, we tested the toxicity of ASA to cultured myoblasts in vitro and its acute systemic toxicity in mice. ASA is a non-toxic small molecule with an LD<sub>50</sub> > 5000 mg/kg. Some background necrotic foci in the liver, kidney and gastrointestinal tract were shown that are likely incidental but warrant follow-up sub-/chronic oral exposure studies. |
| format | Article |
| id | doaj-art-e2ad4744f58a472c8d5150ae8e014a45 |
| institution | Directory of Open Access Journals |
| issn | 1424-8247 |
| language | English |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| spelling | doaj-art-e2ad4744f58a472c8d5150ae8e014a452025-08-19T22:15:14ZengMDPI AGPharmaceuticals1424-82472023-10-011610145810.3390/ph16101458Adenylosuccinic Acid Is a Non-Toxic Small Molecule In Vitro and In VivoCara A. Timpani0Lorna Rasmussen1Emma Rybalka2Institute for Health and Sport (IHeS), Victoria University, Melbourne, VIC 8001, AustraliaCerberus Sciences, Scoresby, VIC 3179, AustraliaInstitute for Health and Sport (IHeS), Victoria University, Melbourne, VIC 8001, AustraliaAdenylosuccinic acid (ASA) is a small molecule dicarboxylate that could be a strong clinical development candidate for inherited myopathies involving dysregulated purine nucleotide metabolism. Currently, there are no published pharmacokinetic/dynamic or toxicology data available, although 10-year clinical trial data on Duchenne muscular dystrophy patients suggests it is a chronically safe drug. In this study, we tested the toxicity of ASA to cultured myoblasts in vitro and its acute systemic toxicity in mice. ASA is a non-toxic small molecule with an LD<sub>50</sub> > 5000 mg/kg. Some background necrotic foci in the liver, kidney and gastrointestinal tract were shown that are likely incidental but warrant follow-up sub-/chronic oral exposure studies.https://www.mdpi.com/1424-8247/16/10/1458adenylosuccinic acidDuchenne muscular dystrophymyopathymetabolic diseaseskeletal muscletoxicology |
| spellingShingle | Cara A. Timpani Lorna Rasmussen Emma Rybalka Adenylosuccinic Acid Is a Non-Toxic Small Molecule In Vitro and In Vivo adenylosuccinic acid Duchenne muscular dystrophy myopathy metabolic disease skeletal muscle toxicology |
| title | Adenylosuccinic Acid Is a Non-Toxic Small Molecule In Vitro and In Vivo |
| title_full | Adenylosuccinic Acid Is a Non-Toxic Small Molecule In Vitro and In Vivo |
| title_fullStr | Adenylosuccinic Acid Is a Non-Toxic Small Molecule In Vitro and In Vivo |
| title_full_unstemmed | Adenylosuccinic Acid Is a Non-Toxic Small Molecule In Vitro and In Vivo |
| title_short | Adenylosuccinic Acid Is a Non-Toxic Small Molecule In Vitro and In Vivo |
| title_sort | adenylosuccinic acid is a non toxic small molecule in vitro and in vivo |
| topic | adenylosuccinic acid Duchenne muscular dystrophy myopathy metabolic disease skeletal muscle toxicology |
| url | https://www.mdpi.com/1424-8247/16/10/1458 |
| work_keys_str_mv | AT caraatimpani adenylosuccinicacidisanontoxicsmallmoleculeinvitroandinvivo AT lornarasmussen adenylosuccinicacidisanontoxicsmallmoleculeinvitroandinvivo AT emmarybalka adenylosuccinicacidisanontoxicsmallmoleculeinvitroandinvivo |