Pre-clinical evaluation of novel small-molecule GPR119 agonists to treat metabolic disorders
This PhD project investigates the preclinical safety, efficacy, and pharmacokinetics (PK) features of novel GPR119 agonists, ps297 and ps318, for metabolic disorders. Both investigational compounds act as GLP-1 secretagogues, showing synergistic effects with sitagliptin. PK analysis confirmed a gut-...
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| Format: | Thesis |
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Curtin University
2025
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| Online Access: | http://hdl.handle.net/20.500.11937/97771 |
| _version_ | 1848766313545072640 |
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| author | Patil, Mohan |
| author_facet | Patil, Mohan |
| author_sort | Patil, Mohan |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | This PhD project investigates the preclinical safety, efficacy, and pharmacokinetics (PK) features of novel GPR119 agonists, ps297 and ps318, for metabolic disorders. Both investigational compounds act as GLP-1 secretagogues, showing synergistic effects with sitagliptin. PK analysis confirmed a gut-oriented mechanism with low bioavailability. Its chronic combination therapy with sitagliptin restored incretin and insulin secretion, glucose homeostasis, and liver health in obese mice. Toxicity assessments indicated safety, supporting further investigation of these gut-oriented agents to treat metabolic disorders. |
| first_indexed | 2025-11-14T11:49:10Z |
| format | Thesis |
| id | curtin-20.500.11937-97771 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T11:49:10Z |
| publishDate | 2025 |
| publisher | Curtin University |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-977712025-05-21T01:29:34Z Pre-clinical evaluation of novel small-molecule GPR119 agonists to treat metabolic disorders Patil, Mohan This PhD project investigates the preclinical safety, efficacy, and pharmacokinetics (PK) features of novel GPR119 agonists, ps297 and ps318, for metabolic disorders. Both investigational compounds act as GLP-1 secretagogues, showing synergistic effects with sitagliptin. PK analysis confirmed a gut-oriented mechanism with low bioavailability. Its chronic combination therapy with sitagliptin restored incretin and insulin secretion, glucose homeostasis, and liver health in obese mice. Toxicity assessments indicated safety, supporting further investigation of these gut-oriented agents to treat metabolic disorders. 2025 Thesis http://hdl.handle.net/20.500.11937/97771 Curtin University restricted |
| spellingShingle | Patil, Mohan Pre-clinical evaluation of novel small-molecule GPR119 agonists to treat metabolic disorders |
| title | Pre-clinical evaluation of novel small-molecule GPR119 agonists to treat metabolic disorders |
| title_full | Pre-clinical evaluation of novel small-molecule GPR119 agonists to treat metabolic disorders |
| title_fullStr | Pre-clinical evaluation of novel small-molecule GPR119 agonists to treat metabolic disorders |
| title_full_unstemmed | Pre-clinical evaluation of novel small-molecule GPR119 agonists to treat metabolic disorders |
| title_short | Pre-clinical evaluation of novel small-molecule GPR119 agonists to treat metabolic disorders |
| title_sort | pre-clinical evaluation of novel small-molecule gpr119 agonists to treat metabolic disorders |
| url | http://hdl.handle.net/20.500.11937/97771 |