A study led by First Health Pharmaceuticals B.V. (FHPBV) and the Italian Institute of oncological research and prevention (ISPRO), together with the University of Siena and the Italian National Research Center (CNR) focused on assessing the antitumor activity of the FHP01 DDX3X helicase inhibitor compound developed by First Health Pharmaceuticals in in vivo breast cancer preclinical models.
FHP01 proved to be highly active against different breast cancer cell types, including triple-negative breast cancer (TNBC) models. Most importantly, the study showed that this small molecule drug candidate works effectively as a standalone treatment rather than in a combination therapy.
DDX3X is an ATP-dependent RNA helicase and part of the DEAD-box helicase family and as such it is able to regulate nearly all stages of RNA metabolism, including transcription and translation. Not only has the role of DDX3X in cancer biology been confirmed, but evidence has shown that its activity is related to tumorigenesis and tumor progression, especially in some types of cancers where DDX3X is particularly overexpressed like breast cancer, head and neck squamous cell carcinoma (HNSSC), lung cancer, etc. Furthermore, DDX3X helicase has shown a high potential of targeted pharmacological approach, thus can be of huge interest especially for precision medicine.
FHP01 potential drug candidate
The individuation of a potentially successful drug candidate started with an in silico approach. After a first selection of a group of molecules through molecular docking at the RNA binding site of DDX3X, the most promising one was subsequently chosen for tests in preclinical models of breast cancer.
The study concluded that by inhibiting DDX3X, the FHP01 molecular compound exerts an actual antiproliferative and killing activity against different breast cancer cell types and strongly inhibits tumor growth while showing, at the same time, no systemic toxicity but good bioavailability in vivo instead.