RK-33

Catalog No.S8246

RK-33 Chemical Structure

Molecular Weight(MW): 428.44

RK-33 is a first-in-class small molecule inhibitor of DDX3 (a RNA helicase) and causes G1 cell cycle arrest, induces apoptosis, and promotes radiation sensitization in DDX3-overexpressing cells.

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Choose Selective DNA/RNA Synthesis Inhibitors

Biological Activity

Description RK-33 is a first-in-class small molecule inhibitor of DDX3 (a RNA helicase) and causes G1 cell cycle arrest, induces apoptosis, and promotes radiation sensitization in DDX3-overexpressing cells.
Targets
DDX3 [1]
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[1].

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A549 cells MUDDfZRwfG:6aXPpeJkh[XO|YYm= NFjGWHE4OiCq MlTpR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gRVU1QSClZXzsd{Bi\nSncjC3NkBpenNiYomgW3NVOSCjc4PhfUwhUUN3ME2yMlUh|ryP NGfydokzOTV5MkW0NS=>
A549 cells NUfzXploS3m2b4TvfIlkcXS7IHHzd4F6 MortO|IhcA>? MVjDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDBOVQ6KGOnbHzzJIFnfGW{IEeyJIhzeyCkeTDXV3QyKGG|c3H5MEBKSzVyPUKuOVYh|ryP NVy1bWlnOjN{OUCyOVI>
H460 cells MWTDfZRwfG:6aXPpeJkh[XO|YYm= M3jnVlczKGh? M3;YVmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGg1PjBiY3XscJMh[W[2ZYKgO|IhcHK|IHL5JHdUXDFiYYPzZZktKEmFNUC9Nk45KM7:TR?= NX2zXoZ5OjF3N{K1OFE>
MDA-MB-231 cells NIK3XXdEgXSxdH;4bYNqfHliYYPzZZk> Mn2wO|IhcA>? NUD1N5BCS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hVUSDLV3CMVI{OSClZXzsd{Bi\nSncjC3NkBpenNiYomgW3NVOSCjc4PhfUwhUUN3ME20MlAyKM7:TR?= MnrhNlE2PzJ3NEG=
PC3 cells MmHZR5l1d3SxeHnjbZR6KGG|c3H5 Mn3iO|IhcA>? NGXpe4ZEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBRSzNiY3XscJMh[W[2ZYKgO|IhcHK|IHL5JHdUXDFiYYPzZZktKEmFNUC9OE45KM7:TR?= M2S3clIyPTd{NUSx
MCF7 cells MVfDfZRwfG:6aXPpeJkh[XO|YYm= NWLLd2tpPzJiaB?= M1PoPGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJG1ETjdiY3XscJMh[W[2ZYKgO|IhcHK|IHL5JHdUXDFiYYPzZZktKEmFNUC9O{42KM7:TR?= NWC0dpR[OjF3N{K1OFE>
OVCAR3 cells M4PnO2N6fG:2b4jpZ4l1gSCjc4PhfS=> NGXmNno4OiCq NV:1WoN1S3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hV1[FQWKzJINmdGy|IHHmeIVzKDd{IHjyd{BjgSCZU2SxJIF{e2G7LDDJR|UxRTF2LkWg{txO MUCyN|I6ODJ3Mh?=

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
DDX3; 

PubMed: 30292066     


Immunoblots showing DDX3 expression levels in medulloblastoma cell lines after treatment with RK-33 for 48 h. 

Cyclin D1 / Cyclin E1 ; 

PubMed: 25820276     


Immunoblot of cell cycle-related proteins (Cyclin D1 and Cyclin E1) and cell death-related proteins (cleaved caspase 7, cleaved caspase 9) in H1299 cells after treatment with RK-33 (10 μM).

30292066 25820276
Growth inhibition assay
Cell viability; 

PubMed: 27634756     


Cell viability assay of RK-33 on PC3, DU145, 22Rv1, and LNCaP. 

27634756
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[1].

Protocol

Cell Research:

[1]

- Collapse
  • Cell lines: MDA-MB-231 cells
  • Concentrations: 7.5 μM
  • Incubation Time: 12 h
  • Method:

    Healthy, 60-70% confluent MDA-MB-231 cells are transduced with shDDX3 lentivirus particles. Knockdown of DDX3 expression is confirmed both by qRT-PCR and immunoblotting. MDA-MB-231 cells are treated with RK-33 (7.5 μM) for 12 h and harvested for RNA. Microarray experiments are performed.


    (Only for Reference)
Animal Research:

[1]

- Collapse
  • Animal Models: SCID mice
  • Formulation: --
  • Dosages: 20 mg/kg
  • Administration: i.p.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 85 mg/mL (198.39 mM)
Water Insoluble
Ethanol Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 428.44
Formula

C23H20N6O3

CAS No. 1070773-09-9
Storage powder
in solvent
Synonyms N/A

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID