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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. PMC7686075
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. PMC9453862
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. PMC7016805
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. PMC6050443
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. PMC6050443
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. PMC9453862
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. PMC7680365
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. PMC7680365
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. PMC7680365
Human lung fibroblasts 1 or 10 μM 48 hours RK-33 inhibited TGF-β1-induced upregulation of NEU3 PMC10132153
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 PMC4492822
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 PMC4492822
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 PMC5756132
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 PMC5756132
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 PMC5756132
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 PMC5756132
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 PMC8048136
Marc-145 cells 8.495 μM 72 hours RK-33 inhibits DDX3X expression and reduces PRRSV replication. PMC11331664
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. PMC6171097
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. PMC6171097
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 PMC4492822
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 PMC4492822
DU145 3 μM (IC50) RK-33 inhibited proliferation and induced G1 phase cell-cycle arrest in DU145 cells. PMC5576499
LNCaP 6 μM (IC50) RK-33 inhibited proliferation and induced G1 phase cell-cycle arrest in LNCaP cells. PMC5576499
22Rv1 3–6 μM (IC50) RK-33 inhibited proliferation and induced G1 phase cell-cycle arrest in 22Rv1 cells. PMC5576499
PC3 12 μM (IC50) RK-33 had minimal effects on PC3 cells, with no significant changes in cell cycle. PMC5576499

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 PMC4492822
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 PMC10132153
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. PMC5576499
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. PMC6171097

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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