Background:

IC50: 4.4-8.4 μM for cancer cell lines with high levels of DDX3 expression (A549, H1299, H23, and H460)

RK-33 is a DDX3 inhibitor.

DDX3 has been identified as a RNA helicase that is overexpressed in various cancer types such as lung cancer and is correlated with lower survival in lung cancer patients.

In vitro: RK-33 was reported to bind to DDX3 and abrogated its activity. Inhibition of DDX3 by RK-33 resulted in G1 cell cycle arrest, induced apoptosis, and promoted radiation sensitization in DDX3-overexpressing cells. Moreover, the loss of DDX3 function caused by RK-33 impaired Wnt signaling via disruption of the DDX3-β-catenin axis [1].

In vivo: The effect of RK-33 with a fractional dosing regimen was studied in the Twist1/KrasG12D lung cancer model. Results showed that during the 3 weeks treatment, a modest decrease in tumor growth with radiation and even more so with the combination of RK-33 and radiation. Therefore, these data indicated that RK-33 in combination with hypofractionated radiation was able to decrease lung tumor load effectively in preclinical lung cancer models and performed much better than the commonly used radiosensitizer carboplatin [1].

Clinical trial: Up to now, RK-33 is still in the preclinical development stage.

Reference:
[1] Bol GM et al.  Targeting DDX3 with a small molecule inhibitor for lung cancer therapy. EMBO Mol Med. 2015 Mar 27;7(5):648-69.