RK-33 | DDX3 inhibitor | CAS#1070773-09-9

RK-33
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 406835

CAS#: 1070773-09-9

Description: RK-33 is a potent and selective 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.

Chemical Structure

RK-33

CAS# 1070773-09-9

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 406835
Name: RK-33
CAS#: 1070773-09-9
Chemical Formula: C23H20N6O3
Exact Mass: 428.16
Molecular Weight: 428.450
Elemental Analysis: C, 64.48; H, 4.71; N, 19.62; O, 11.20

Price and Availability

Size	Price	Availability	Quantity
1g	USD 3450
2g	USD 6250
5g	USD 12950
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: RK-33; RK 33; RK33.

IUPAC/Chemical Name: 3,7-dihydro-3,7-bis[(4-methoxyphenyl)methyl]-2H-diimidazo[4,5-d:4',5'-f][1,3]diazepin-2-one

InChi Key: COUMZXFUZDBRCZ-UHFFFAOYSA-N

InChi Code: 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

SMILES Code: O=C1N(CC2=CC=C(OC)C=C2)C3=NC=NC4=C(N=CN4CC5=CC=C(OC)C=C5)C3=N1

Appearance: Solid powder

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

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:

Product Data

Instruction:

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Biological target:	RK-33 is an inhibitor of DDX3 and causes G1 cell cycle arrest, induces apoptosis, and promotes radiation sensitization in DDX3-overexpressing cells.
In vitro activity:	This study supports the use of RK-33 as a host-targeted antiviral strategy to control SARS-CoV-2 infection. Targeting DDX3 with RK-33 reduced the viral load in four isolates of SARS-CoV-2 by one to three log orders in Calu-3 cells. Proteomics and RNA-seq analyses indicated that most SARS-CoV-2 genes were downregulated by RK-33 treatment. Reference: Front Microbiol. 2022 Aug 25;13:959577. https://pubmed.ncbi.nlm.nih.gov/36090095/
In vivo activity:	RK-33 inhibits DDX3 activity and down-regulates WNT/β-catenin signaling. It could be used as a therapeutic strategy for DDX3-expressing medulloblastomas in combination with radiation.The combination of RK-33 and 5 Gy radiation caused tumor regression in a mouse xenograft model of medulloblastoma. The researchers observed DDX3 expression in both pediatric (55%) and adult (66%) medulloblastoma patients. Reference: Transl Oncol. 2019 Jan;12(1):96-105. https://pubmed.ncbi.nlm.nih.gov/30292066/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMSO	40.0	93.36

Preparing Stock Solutions

The following data is based on the product molecular weight 428.45 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:	1. Vesuna F, Akhrymuk I, Smith A, Winnard PT Jr, Lin SC, Panny L, Scharpf R, Kehn-Hall K, Raman V. RK-33, a small molecule inhibitor of host RNA helicase DDX3, suppresses multiple variants of SARS-CoV-2. Front Microbiol. 2022 Aug 25;13:959577. doi: 10.3389/fmicb.2022.959577. PMID: 36090095; PMCID: PMC9453862. 2. Xie M, Vesuna F, Tantravedi S, Bol GM, Heerma van Voss MR, Nugent K, Malek R, Gabrielson K, van Diest PJ, Tran PT, Raman V. RK-33 Radiosensitizes Prostate Cancer Cells by Blocking the RNA Helicase DDX3. Cancer Res. 2016 Nov 1;76(21):6340-6350. doi: 10.1158/0008-5472.CAN-16-0440. Epub 2016 Sep 12. PMID: 27634756; PMCID: PMC5576499. 3. Tantravedi S, Vesuna F, Winnard PT Jr, Martin A, Lim M, Eberhart CG, Berlinicke C, Raabe E, van Diest PJ, Raman V. Targeting DDX3 in Medulloblastoma Using the Small Molecule Inhibitor RK-33. Transl Oncol. 2019 Jan;12(1):96-105. doi: 10.1016/j.tranon.2018.09.002. Epub 2018 Oct 3. PMID: 30292066; PMCID: PMC6171097. 4. Chen W, Pilling D, Gomer RH. The mRNA-binding protein DDX3 mediates TGF-β1 upregulation of translation and promotes pulmonary fibrosis. JCI Insight. 2023 Apr 10;8(7):e167566. doi: 10.1172/jci.insight.167566. PMID: 36821384; PMCID: PMC10132153.
In vitro protocol:	1. Vesuna F, Akhrymuk I, Smith A, Winnard PT Jr, Lin SC, Panny L, Scharpf R, Kehn-Hall K, Raman V. RK-33, a small molecule inhibitor of host RNA helicase DDX3, suppresses multiple variants of SARS-CoV-2. Front Microbiol. 2022 Aug 25;13:959577. doi: 10.3389/fmicb.2022.959577. PMID: 36090095; PMCID: PMC9453862. 2. Xie M, Vesuna F, Tantravedi S, Bol GM, Heerma van Voss MR, Nugent K, Malek R, Gabrielson K, van Diest PJ, Tran PT, Raman V. RK-33 Radiosensitizes Prostate Cancer Cells by Blocking the RNA Helicase DDX3. Cancer Res. 2016 Nov 1;76(21):6340-6350. doi: 10.1158/0008-5472.CAN-16-0440. Epub 2016 Sep 12. PMID: 27634756; PMCID: PMC5576499.
In vivo protocol:	1. Tantravedi S, Vesuna F, Winnard PT Jr, Martin A, Lim M, Eberhart CG, Berlinicke C, Raabe E, van Diest PJ, Raman V. Targeting DDX3 in Medulloblastoma Using the Small Molecule Inhibitor RK-33. Transl Oncol. 2019 Jan;12(1):96-105. doi: 10.1016/j.tranon.2018.09.002. Epub 2018 Oct 3. PMID: 30292066; PMCID: PMC6171097. 2. Chen W, Pilling D, Gomer RH. The mRNA-binding protein DDX3 mediates TGF-β1 upregulation of translation and promotes pulmonary fibrosis. JCI Insight. 2023 Apr 10;8(7):e167566. doi: 10.1172/jci.insight.167566. PMID: 36821384; PMCID: PMC10132153.

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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.

6: Bol GM, Vesuna F, Xie M, Zeng J, Aziz K, Gandhi N, Levine A, Irving A, Korz D, Tantravedi S, Heerma van Voss MR, Gabrielson K, Bordt EA, Polster BM, Cope L, van der Groep P, Kondaskar A, Rudek MA, Hosmane RS, van der Wall E, van Diest PJ, Tran PT, Raman V. Targeting DDX3 with a small molecule inhibitor for lung cancer therapy. EMBO Mol Med. 2015 Mar 27;7(5):648-69. doi: 10.15252/emmm.201404368. PubMed PMID: 25820276; PubMed Central PMCID: PMC4492822.

7: Rzeski W, Paduch R, Klatka J, Kandefer-Szerszeń M, Stepulak A, Pozarowski P, Zdzisińska B. Establishment and preliminary characterization of two cell lines derived from larynx carcinoma. Folia Histochem Cytobiol. 2002;40(2):195-6. PubMed PMID: 12056642.

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