borussertib

Borussertib is a **first-in-class covalent-allosteric inhibitor** of protein kinase Akt (also known as AKT1), exhibiting nanomolar potency (IC50 = 0.8 nM, Ki = 2.2 nM for Aktwt)[1][5][7][12]. It selectively and covalently binds to non-catalytic cysteines on the kinase, stabilizing its inactive conformation, and prevents downstream AKT-driven oncogenic signaling[5][8][13]. Borussertib demonstrates strong antiproliferative activity in cancer cell lines with alterations in the PTEN, PI3K, and RAS signaling pathways, and shows synergistic antitumor effects in combination with the MEK inhibitor trametinib, especially in KRAS mutant pancreatic and colorectal cancer models[5][6][9][11][13]. Originally developed for research use, its pharmacokinetic properties currently limit its use to preclinical studies[6]. The originator of borussertib is the University of Dortmund[9].