RK-33 (1070773-09-9) is an inhibitor of the RNA helicase DDX3 – IC50’s = 4.4-8.4 μM in high DDX3 expressing lung cancer cell lines A549, H1299, H23, and H460.1,2?Inhibition of DDX3 led to activation of cell death pathways, inhibition of Wnt pathway signaling, and abrogation of non-homologous end-joining (NHEJ) DNA repair. RK-33 was also active in colorectal cancer?3, prostate cancer4, and medulloblastoma cancer5?cell lines. RK-33 caused radiosensitization in breast cancer through inhibition of mitochondrial translation.6?RK-33 facilitates differentiation in human embryonic stem cells (hESC) and decreases pluripotency markers as well as reducing teratoma formation.7
RK 33 is an inhibitor of DDX3, an ATP-dependent RNA helicase (1). Aberrant regulation of DDX3 is related to various diseases such as prostate and breast cancer (2). RK 33 was shown to decrease proliferation of prostate cancer cells and induced a G1 phase cell-cycle arrest (2).
1) Kondaskar?et al.?(2011),?Novel, Broad Spectrum Anticancer Agents Containing the Tricyclic 5:7:5-Fused Diimidazodiazepine Ring System; ACS Med. Chem. Lett.,?2?252
2) Bol?et al.?(2015),?Targeting DDX3 with a small molecule inhibitor for lung cancer therapy; EMBO Mol. Med.,?7?648
3) Heerma van Voss?et al.?(2015),?Identification of the DEAD box RNA helicase DDX3 as a therapeutic target in colorectal cancer; Oncotarget,?6?28312
4) Xie?et al.?(2016),?RK-33 Radiosensitizes Prostate Cancer Cells by Blocking the RNA Helicase DDX3; Cancer Res.,?76?6340
5) Tantravedi?et al.?(2019),?Targeting DDX3 in Medulloblastoma Using the Small Molecule Inhibitor RK-33; Transl. Oncol.,?12?96
6) Heerma van Voss?et al.?(2018),?Targeting mitochondrial translation by inhibiting DDX3: a novel radiosensitization strategy for cancer treatment;?Oncogene,?37?63
7) Kerr?et al.?(2019),?Targeting RNA helicase DDX3 in stem cell maintenance and teratoma formation; Genes Cancer,?10?11
