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Chemical Structure| 1070773-09-9 Chemical Structure| 1070773-09-9

Structure of RK-33
CAS No.: 1070773-09-9

Chemical Structure| 1070773-09-9

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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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Product Details of RK-33

CAS No. :1070773-09-9
Formula : C23H20N6O3
M.W : 428.44
SMILES Code : O=C1N(CC2=CC=C(OC)C=C2)C3=NC=NC4=C(N=CN4CC5=CC=C(OC)C=C5)C3=N1
MDL No. :MFCD30489740
InChI Key :COUMZXFUZDBRCZ-UHFFFAOYSA-N
Pubchem ID :46184988

Safety of RK-33

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of RK-33

DNA

Isoform Comparison

Biological Activity

Target
  • helicase

In Vitro:

Cell Line
Concentration Treated Time Description References
U2OS human osteosarcoma cells 6 µM 1 hour To evaluate the effect of RK-33 on SG assembly, the results showed that RK-33 significantly inhibited the assembly of G3BP1-positive SGs. Biochem Pharmacol. 2020 Dec;182:114280.
RD cells 1 µM 1 hour To study the effect of RK-33 on HCoV-OC43 infection, results showed that RK-33 significantly reduced viral titers. Front Microbiol. 2022 Aug 25;13:959577.
Vero cells 0.01, 0.04, 0.16, 0.63, 1.25, 2.5, 10, 20, 50 µM 22 hours To test the inhibitory effect of RK-33 on various viruses, results showed that RK-33 effectively inhibited the replication of DENV-2, ZIKV, WNV, RSV, and hPIV-3. Cells. 2020 Jan 9;9(1):170.
MDA-MB-435 cells 4.5 µM 24 hours To evaluate changes in the protein landscape after RK-33 treatment, changes in mitochondrial translation, cell division, and cell cycle-related proteins were observed. Transl Oncol. 2018 Jun;11(3):755-763.
MCF7 cells 1.5 µM, 3 µM, 4.5 µM 24 hours To evaluate the effect of RK-33 on the cell cycle using the FUCCI system, a delay in all cell cycle phases was observed. Transl Oncol. 2018 Jun;11(3):755-763.
Calu-3 cells 5 µM 24 hours To study the effect of RK-33 on SARS-CoV-2 infection, results showed that RK-33 significantly reduced viral load and downregulated most SARS-CoV-2 gene expressions. Front Microbiol. 2022 Aug 25;13:959577.
SW1990 SP cells 4.32 µM (IC50) 48 hours To evaluate the effect of RK-33 on cancer stem cell markers, results showed that RK-33 significantly downregulated the expression of CD44v6, NANOG, SOX9, and β-CATENIN. Gastroenterology. 2020 Nov;159(5):1898-1915.e6.
Capan1 SP cells 5.53 µM (IC50) 48 hours To evaluate the effect of RK-33 on cancer stem cell markers, results showed that RK-33 significantly downregulated the expression of CD44v6, NANOG, SOX9, and β-CATENIN. Gastroenterology. 2020 Nov;159(5):1898-1915.e6.
9–26 NP fibroblasts 9.23 µM (IC50) 48 hours To evaluate the effect of RK-33 on normal fibroblasts, results showed that RK-33 had lower toxicity to normal cells. Gastroenterology. 2020 Nov;159(5):1898-1915.e6.
Human lung fibroblasts 1 or 10 µM 48 hours RK-33 inhibited TGF-β1-induced upregulation of NEU3 JCI Insight. 2023 Apr 10;8(7):e167566.
A549 cells (high DDX3 expression) 1 µM and 2 µM 72 hours To evaluate the cytotoxicity of RK-33 on lung cancer cells, results showed that cells with high DDX3 expression were more sensitive to RK-33 EMBO Mol Med. 2015 May;7(5):648-69.
H3255 cells (low DDX3 expression) 1 µM and 2 µM 72 hours To evaluate the cytotoxicity of RK-33 on lung cancer cells, results showed that cells with high DDX3 expression were more sensitive to RK-33 EMBO Mol Med. 2015 May;7(5):648-69.
MCF10A 7.4 µM (IC50) 72 hours To evaluate the cytotoxicity of RK-33 on normal breast cells MCF10A, results showed that MCF10A was less sensitive to RK-33 Oncogene. 2018 Jan 4;37(1):63-74.
MCF7 2.8–4.5 µM (IC50) 72 hours To evaluate the cytotoxicity of RK-33 on breast cancer cells MCF7, results showed that MCF7 was more sensitive to RK-33 Oncogene. 2018 Jan 4;37(1):63-74.
MDA-MB-231 2.8–4.5 µM (IC50) 72 hours To evaluate the cytotoxicity of RK-33 on breast cancer cells MDA-MB-231, results showed that MDA-MB-231 was more sensitive to RK-33 Oncogene. 2018 Jan 4;37(1):63-74.
MDA-MB-435 2.8–4.5 µM (IC50) 72 hours To evaluate the cytotoxicity of RK-33 on breast cancer cells MDA-MB-435, results showed that MDA-MB-435 was more sensitive to RK-33 Oncogene. 2018 Jan 4;37(1):63-74.
Rat primary cortical neurons 1 µM 72 hours To validate the neuroprotective effects of RK-33 against the combined neurotoxicity of HIV Tat and cocaine, results showed RK-33 significantly reduced neuronal death J Neuroimmune Pharmacol. 2020 Jun;15(2):209-223.
Marc-145 cells 8.495 µM 72 hours RK-33 inhibits DDX3X expression and reduces PRRSV replication. Vet Res. 2024 Aug 18;55(1):103.
DAOY cells 2.5 µM 72 hours RK-33 inhibited the growth and promoted cell death in DAOY cells with an IC50 value of 2.5 μM. Transl Oncol. 2019 Jan;12(1):96-105.
UW228 cells 3.5 µM 72 hours RK-33 inhibited the growth and promoted cell death in UW228 cells with an IC50 value of 3.5 μM. Transl Oncol. 2019 Jan;12(1):96-105.
A549, H1299, H23, and H460 cells 4.4–8.4 µM (IC50) To evaluate the cytotoxicity of RK-33 on lung cancer cells, results showed that cells with high DDX3 expression were more sensitive to RK-33 EMBO Mol Med. 2015 May;7(5):648-69.
H3255 cells > 25 µM (IC50) To evaluate the cytotoxicity of RK-33 on lung cancer cells, results showed that cells with high DDX3 expression were more sensitive to RK-33 EMBO Mol Med. 2015 May;7(5):648-69.
DU145 3 µM (IC50) RK-33 inhibited proliferation and induced G1 phase cell-cycle arrest in DU145 cells. Cancer Res. 2016 Nov 1;76(21):6340-6350.
LNCaP 6 µM (IC50) RK-33 inhibited proliferation and induced G1 phase cell-cycle arrest in LNCaP cells. Cancer Res. 2016 Nov 1;76(21):6340-6350.
22Rv1 3–6 µM (IC50) RK-33 inhibited proliferation and induced G1 phase cell-cycle arrest in 22Rv1 cells. Cancer Res. 2016 Nov 1;76(21):6340-6350.
PC3 12 µM (IC50) RK-33 had minimal effects on PC3 cells, with no significant changes in cell cycle. Cancer Res. 2016 Nov 1;76(21):6340-6350.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Twist1/KrasG12D autochthonous lung tumor model Intraperitoneal injection 20 mg/kg Twice a week for 7 weeks To evaluate the effect of RK-33 in combination with radiation, results showed that RK-33 significantly enhanced radiation-induced tumor regression EMBO Mol Med. 2015 May;7(5):648-69.
C57BL/6 mice Bleomycin-induced pulmonary fibrosis model Intraperitoneal injection 20 mg/kg Every 2 days for 11 days RK-33 potentiated survival, reduced lung inflammation and fibrosis, and decreased tissue levels of DDX3, TGF-β1, and NEU3 JCI Insight. 2023 Apr 10;8(7):e167566.
SCID mice DU145-Luc xenograft model Intraperitoneal injection 50 mg/kg Thrice weekly for two weeks The combination of RK-33 and radiation significantly reduced tumor growth and induced more apoptosis. Cancer Res. 2016 Nov 1;76(21):6340-6350.
Nude mice Medulloblastoma xenograft model Intraperitoneal injection 50 mg/kg Every alternate day for two weeks The combination of RK-33 and 5 Gy radiation caused tumor regression in a mouse xenograft model of medulloblastoma. Transl Oncol. 2019 Jan;12(1):96-105.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.33mL

0.47mL

0.23mL

11.67mL

2.33mL

1.17mL

23.34mL

4.67mL

2.33mL

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