kt-5000AI

kt-5000AI: first-in-class CNS-penetrant ATR inhibitors

Ataxia telangiectasia and Rad3-related protein serine/threonine kinase (ATR) plays a crucial role in regulating DNA damage repair. ATR acts as a central “guardian” in the DNA damage response, helping cancer cells survive replication stress. Inhibition prevents this guardian from repairing the damaged DNA, thereby killing the cancer cell.

ATR inhibitors currently in clinical development have limited CNS-penetration and are therefore sub-optimal for the treatment of brain tumors and brain metastases. Rakovina is developing a library of ATR inhibitor compound drug candidates with CNS-penetration.

Additionally, Rakovina’s most recent KT-5000AI compounds are designed to co-inhibit ATR and mTOR in a single small molecule. 

Tumors with PTEN loss are often especially vulnerable to ATR inhibition, but PTEN deficiency can also activate mTOR as an alternative survival pathway, creating a potential escape route under ATR-only treatment. These compounds are also engineered for blood–brain barrier penetration, a critical unmet need in primary brain cancers and cancers with a high risk of brain metastasis. To our knowledge, this ATR/mTOR + CNS-penetrant combination has not previously been designed as a single therapeutic agent.

Read our SNO 2025 data release highlighting AI-designed, CNS-penetrant ATR/mTOR inhibitors, including enzymatic potency comparisons and CNS exposure findings: Rakovina Therapeutics Showcases Compelling Preclinical Data on AI-Discovered CNS-Penetrant ATR/mTOR Inhibitors at SNO 2025.