ENGA-L08E

ENGA-L08E is a novel homo-aza-steroidal alkylating ester, designed as an anticancer agent. It is a hybrid molecule based on an estrone-modified steroidal skeleton conjugated with an alkylating agent. ENGA-L08E acts as a dual inhibitor of the **PI3K-AKT** and **KRAS-ERK** signaling pathways, important for cancer cell survival and proliferation. Preclinical studies demonstrate that it inhibits phosphorylation of AKT1/2 and ERK1/2, showing significant cytostatic and cytotoxic effects against multiple human ovarian carcinoma cell lines, including those resistant to standard alkylating agents and independent of key mutations (TP53, KRAS, MEK1, PIK3CA) and BRCA1 status. In vivo, ENGA-L08E showed greater antitumor efficacy and a lower toxicity profile than reference alkylators.