Rakovina Therapeutics Showcases Compelling Preclinical Data on AI-Discovered CNS-Penetrant ATR/mTOR Inhibitors at the 2025 Society for Neuro-Oncology Annual Meeting
Rakovina Therapeutics presented compelling preclinical results on AI-discovered central nervous system (CNS)-penetrant ATR/mTOR dual inhibitors at the 2025 Society for Neuro-Oncology (SNO) Annual Meeting in Honolulu, Hawaii2379.
The compounds were designed using the Enki™ generative AI platform from Variational AI, specifically to cross the blood–brain barrier and target tumor cells within the CNS235.
ATR and mTOR are two key cancer-driving pathways, and Rakovina’s inhibitors represent the first examples of a single small-molecule agent engineered to modulate both, with CNS penetration23.
Lead molecules demonstrated >50% ATR inhibition at 1 µM and showed comparable or superior enzymatic potency relative to current clinical ATR inhibitors such as ceralasertib, tuvusertib, and elimusertib, while maintaining PIKK-family selectivity23.
The dual inhibition strategy is aimed at overcoming resistance mechanisms in PTEN-deficient cancers, which are highly dependent on ATR and mTOR signaling—particularly those with a high risk of CNS metastasis (such as ovarian, lung, breast, and melanoma tumors)23.
Pharmacokinetic profiling in mice showed that these compounds are well-tolerated, metabolically stable in human liver microsomes, and achieve measurable exposure within the brain23.
Rakovina generated a virtual library of 138 predicted compounds, synthesizing 43 for biochemical and cellular evaluation; multiple showed promising pharmacological profiles for further development in brain tumor models23.
These results mark a significant milestone for Rakovina’s AI-enabled drug discovery pipeline, aiming to advance candidates for clinical evaluation in collaboration with industry partners239.
Sources:
2. https://www.biospace.com/press-releases/rakovina-therapeutics-showcases-compelling-preclinical-data-on-ai-discovered-cns-penetrant-atr-mtor-inhibitors-at-the-2025-society-for-neuro-oncology-annual-meeting
3. https://www.rakovinatherapeutics.com/rakovina-therapeutics-showcases-compelling-preclinical-data-on-ai-discovered-cns-penetrant-atr-mtor-inhibitors-at-the-2025-society-for-neuro-oncology-annual-meeting/
5. https://investingnews.com/rakovina-therapeutics-to-present-new-data-highlighting-cns-penetrant-atr-and-parp1-inhibitors-at-the-2025-society-for-neuro-oncology-annual-meeting/