Saccharin-Enabled Oral Formulation, Biopharmaceutics and Early Genotoxicity Assessment of the PPARγ Antagonist T0070907

Background/Objectives: T0070907 is a potent PPARγ antagonist with emerging antitumour activity in osteosarcoma; however, its very low aqueous solubility, uncertain systemic exposure, and nitroaromatic structure raise significant developability concerns. This work aimed to convert T0070907 into a pharmaceutically tractable oral entity and generate an integrated early developability and genotoxicity snapshot. Methods: The physicochemical properties of T0070907 were characterised, solubility-enhancing strategies were evaluated, and saccharin was identified as a supramolecular excipient enabling high-dose oral delivery. A 20 mg/mL oral liquid formulation was developed and monitored using a validated, stability-indicating UHPLC/LC–MS method. In vivo systemic and tissue exposure was assessed in rats using LC–MS/MS; hepatic metabolism was explored in human liver microsomes; and genotoxicity risk was evaluated both in silico (ICH M7) and in a GLP-compliant Ames test. Results: Saccharin markedly enhanced solubility and enabled a 20 mg/mL oral formulation that remained stable for 90 days, with pyridin-4-amine identified as the dominant degradation product. In rats, T0070907 was below the limit of quantification in plasma after oral dosing at 5, 10 and 100 mg/kg, including in a solubilising vehicle. In contrast, T0070907 was clearly mutagenic in the Ames test. Conclusions: These findings support saccharin-based supramolecular formulations as a practical strategy for poorly soluble nitrobenzamides, while positioning T0070907 primarily as a pharmacological tool.