FDA approves phase I clinical trial to evaluate XL114 in patients with non-Hodgkin lymphoma

XL114 is a novel anticarcinogenic agent that induces inhibitory effects on aberrant CARD11-BCL10-MALT1 (CBM) signaling complex. This complex triggers the adaptive immune response and mediates lymphocyte proliferation and survival.

In vitro experiments have indicated the anticarcinomic activity of XL114 against a variety of blood cancers and tumors:

• It demonstrated antiproliferative activity in cell lines for B-cell-like diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and follicular lymphoma (FL) cell lines by regulating the aberrant activity of CBM signaling pathway.
• Additionally, XL114 exhibited dose-dependent inhibition of tumor growth in an activated B-cell (ABC)-DLBCL mouse xenograft tumor model.
• Furthermore, this investigational molecule has shown to be precisely selective against a range of enzymes and receptors. This has led to the identification of the fatty acid-binding protein 5 (FABP5) as one of the binding targets for this molecule.

Nevertheless, further investigation is required to completely understand the molecular basis of XL114’s inhibitory actions for BCR signaling and MALT1 activation.

These preclinical investigations have demonstrated that XL114 has the potential to be used as an anticancer agent in non-Hodgkin lymphoma (NHL) and other malignancies. Recently, the U.S. Food and Drug Administration (FDA) has approved the evaluation of XL114 in patients with NHL, to be used as an anticancerous agent in a phase I clinical trial.