RK-33, DDX3 inhibitor

DDX3 inhibitor RK-33 binds to DDX3 and abrogates its activity. Inhibition of DDX3 by RK-33 caused G1 cell cycle arrest, induced apoptosis, and promoted radiation sensitization in DDX3-overexpressing cells. Overall, inhibition of DDX3 by RK-33 promotes tumor regression, thus providing a compelling argument to develop DDX3 inhibitors for lung cancer therapy. RK-33 radiosensitizes prostate cancer cells by blocking the RNA helicase DDX3.

Product information

CAS Number: 1070773-09-9

Molecular Weight: 428.44

Formula: C23H20N6O3

Synonym:

RK 33

RK33

RK-33

Chemical Name: 5, 11-bis[(4-methoxyphenyl)methyl]-3, 5, 7, 9, 11, 13-hexaazatricyclo[8.3.0.0, ]trideca-1(10), 2, 6, 8, 12-pentaen-4-one

Smiles: COC1C=CC(CN2C(=O)N=C3C2=NC=NC2=C3N=CN2CC2C=CC(=CC=2)OC)=CC=1

InChiKey: COUMZXFUZDBRCZ-UHFFFAOYSA-N

InChi: InChI=1S/C23H20N6O3/c1-31-17-7-3-15(4-8-17)11-28-14-26-19-20-22(25-13-24-21(19)28)29(23(30)27-20)12-16-5-9-18(32-2)10-6-16/h3-10,13-14H,11-12H2,1-2H3

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Solubility (25°C) DMSO: 85 mg/mL(198.39 mM). Water: Insoluble.

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

RK-33 binds specifically to DDX3, but not to the closely related proteins DDX5 and DDX17. RK-33 inhibits cancer growth and radiosensitizes lung cancer cells in a DDX3-dependent manner. RK-33 has no effect on either mitochondrial respiration or ATP generation. RK-33 curbs proliferation and induces apoptosis in a DDX3-dependent fashion. Wnt signaling is mediated by DDX3 and inhibited by RK-33. RK-33 impairs radiation-induced DNA damage repair by inhibiting NHEJ activity.

In Vivo:

RK-33 in combination with radiation induces tumor regression in multiple mouse models of lung cancer. RK-33, at the dose used, is non-toxic in SCID mice. RK-33-treated mice do not exhibit any discernable morphological changes.

References:

1. Xie M, Vesuna F, Tantravedi S, Bol GM, Heerma van Voss MR, Nugent K, Malek R, Gabrielson KL, Van Diest PJ, Tran PT, Raman V. RK-33 radiosensitizes prostate cancer cells by blocking the RNA helicase DDX3. Cancer Res. 2016 Sep 12. pii: canres.0440.2016. [Epub ahead of print] PubMed PMID: 27634756.
2. Wilky BA, Kim C, McCarty G, Montgomery EA, Kammers K, DeVine LR, Cole RN, Raman V, Loeb DM. RNA helicase DDX3: a novel therapeutic target in Ewing sarcoma. Oncogene. 2016 May 19;35(20):2574-83. doi: 10.1038/onc.2015.336. Epub 2015 Sep 14. PubMed PMID: 26364611.
3. Bol GM, Khan R, Heerma van Voss MR, Tantravedi S, Korz D, Kato Y, Raman V. PLGA nanoparticle formulation of RK-33: an RNA helicase inhibitor against DDX3. Cancer Chemother Pharmacol. 2015 Oct;76(4):821-7. doi: 10.1007/s00280-015-2851-3. Epub 2015 Sep 2. PubMed PMID: 26330329; PubMed Central PMCID: PMC4878412.
4. Heerma van Voss MR, Vesuna F, Trumpi K, Brilliant J, Berlinicke C, de Leng W, Kranenburg O, Offerhaus GJ, Bürger H, van der Wall E, van Diest PJ, Raman V. Identification of the DEAD box RNA helicase DDX3 as a therapeutic target in colorectal cancer. Oncotarget. 2015 Sep 29;6(29):28312-26. doi: 10.18632/oncotarget.4873. PubMed PMID: 26311743; PubMed Central PMCID: PMC4695062.
5. Burkadze G, Kikalishvili N, Kargareteli V. Application of nano composites in the fixation and processing of histological material. Georgian Med News. 2015 Apr;(241):77-83. PubMed PMID: 25953945.

Products are for research use only. Not for human use.