Name: RRx-001
Brand: GlpBio
SKU: GC32066
Availability: InStock
Rating: 5 (19 reviews)

GlpBio Products Cited In Reputable Papers

Nature
610.7931 (2022): 366-372

Nature
618, 1017–1023 (2023)

Cell
183.7 (2020): 1867-1883

Cell Research
31, 1291–1307 (2021)

Cell Research
33, 273–287 (2023)

Cell Research
33, 546–561 (2023)

Molecular Cancer
21.1 (2022): 1-17

Molecular Cancer
21.1 (2022): 1-18

Cancer Cell
39 (2021): 1-16

Cell Host Microbe
30.8 (2022): 1124-1138

Cell Host Microbe
31.5 (2023): 766-780

Cell Host Microbe
31.3 (2023): 418-43

Cell Metabolism
34.2 (2022): 240-255

Ann Rheum Dis
82(4): 533-545 (2023)

Cell Mol Immunol
20, 264–276 (2023)

Adv Funct Mater
33.35 (2023): 2214998

Product Documents

Quality Control & SDS

View current batch:

Purity: >99.50%

Protocol

Cell experiment [1]:
Cell lines	Human cancer cell lines HEP-G2, HT-29, CACO-2
Preparation Method	The MTT proliferation assay kit was used to detect cell growth and proliferation. 5 103 cells were seeded in each well of a 96-well plate, treated with (or without) compound (RRx-001) and cultured for up to 72 h. Then 10 µL was added to each well
Reaction Conditions	5, 50, 100 mM RRx-001 for 72h
Applications	RRx-001 affects glucose and G6PD enzyme activity in three different cancer cell lines namely Hep G2, CACO-2, and HT-29. In all cancer cell lines tested, RRx-001 induced G6PD inhibition in a concentration dependent fashion.
Animal experiment [2]:
Animal models	Nude mice, male, 7-8 weeks old and 20-25 grams in body weight
Preparation Method	Tumors were imaged for basal FLUC, RLUC, and mRFP signals 24 h before administration of RRx-001. Following injection with RRx-001, mice were imaged for RLUC signal by intravenous injection of 50 µg of coelenterazine at 8 and 24 h post-RRx-001 treatment.
Dosage form	10 mg/kg RRx-001( i.v.)
Applications	Mice were imaged for ARE-FLUC expression 24 h before and after RRx-001 administration. Results showed that a single dose of 10 mg/kg RRx-001 inhibited tumor growth and produced a tumor volume quadrupling time of 5.7±1.3 days compared to 3.3±0.7 days of vehicle control group.
References: [1].Oronsky B, Scicinski J, et,al.RRx-001, a novel clinical-stage chemosensitizer, radiosensitizer, and immunosensitizer, inhibits glucose 6-phosphate dehydrogenase in human tumor cells. Discov Med. 2016 Apr;21(116):251-65. PMID: 27232511. [2]. Ning S, Sekar TV, et,al.Nrf2 activity as a potential biomarker for the pan-epigenetic anticancer agent, RRx-001. Oncotarget. 2015 Aug 28;6(25):21547-56. doi: 10.18632/oncotarget.4249. PMID: 26280276; PMCID: PMC4673285.

RRx-001 is an aerospace-derived anticancer agent with reactive nitrogen species (RNS)-generating chemistry that leads to epigenetic alterations, such as DNA methylation and histone acetylation in cancer cells^[4,7]. Apart from epigenetic alterations, RRx-001 acts via pleiotropic mechanisms including redox signaling and redox-induced dysregulation of many different signal pathways such as Nrf2, p53, PARP cleavage, HIF1 alpha, and G6PD activity^[5]. RRx-001 also triggers p53 and p21 activity in response to double-stranded DNA breaks as well as deregulates cancer cellular energetics and metabolism^[6].

Rx-001 affects glucose and G6PD enzyme activity in three different cancer cell lines namely Hep G2, CACO-2, and HT-29. In all cancer cell lines tested, RRx-001 induced G6PD inhibition in a concentration dependent fashion^[1]. RRx-001 mediated nuclear translocation of Nrf2 and the activation of expression of its downstream enzymes HO-1 and NQO1 in tumor cells. Inhibition of intrinsic Nrf2 expression by Nrf2-specific siRNA increased cell sensitivity to RRx-001^[2]. The increase in the synthesis and release of cytokines and the up-regulation of pro-inflammatory factors in LPS-treated microglial cells were significantly reduced by RRx-001 pretreatment. As the most classical inflammatory pathways, NF-κB and MAPK signaling pathways were activated by LPS, but were inhibited by RRx-001^[9].

Molecular imaging of tumor cells co-expressing pARE-Firefly luciferase and pCMV-Renilla luciferase-mRFP in vitro and in vivo in mice revealed that RRx-001 significantly increased ARE-FLUC signal in cells in a dose- and time-dependent manner, suggesting that RRx-001 is an effective activator of the Nrf2-ARE signaling pathway^[2]. RRx-001 plays a role in short-term blood flow redistribution in tumors enriched in percutaneous cells and α-SMA vessels^[3]. One hour following administration of 99mTc labeled RBCs treated with 10 mg/kg RRx-001, An approximate 2.0-fold and 1.5-fold increase in 99mTc-labeled RBCs compared to vehicle control in HEPG2 and HT-29 tumor models, respectively. An approximate 40% and 36% decrease in HEP-G2 and HT-29 tumor weight, respectively, following treatment with RRx-001^[8].

References:
[1]. Oronsky B, Scicinski J, et,al. RRx-001, a novel clinical-stage chemosensitizer, radiosensitizer, and immunosensitizer, inhibits glucose 6-phosphate dehydrogenase in human tumor cells. Discov Med. 2016 Apr;21(116):251-65. PMID: 27232511.
[2]. Ning S, Sekar TV, et,al. Nrf2 activity as a potential biomarker for the pan-epigenetic anticancer agent, RRx-001. Oncotarget. 2015 Aug 28;6(25):21547-56. doi: 10.18632/oncotarget.4249. PMID: 26280276; PMCID: PMC4673285.
[3]. Oronsky B, Scicinski J, et,al. RRx-001, an epigenetic-based radio- and chemosensitizer, has vascular normalizing effects on SCCVII and U87 tumors. Clin Epigenetics. 2016 May 11;8:53. doi: 10.1186/s13148-016-0220-7. PMID: 27175220; PMCID: PMC4864927.
[4]. Ning S, Bednarski M, et,al.Dinitroazetidines are a novel class of anticancer agents and hypoxia-activated radiation sensitizers developed from highly energetic materials. Cancer Res. 2012 May 15;72(10):2600-8. doi: 10.1158/0008-5472.CAN-11-2303. PMID: 22589277.
[5]. Magesh S, Chen Y, et,al. Small molecule modulators of Keap1-Nrf2-ARE pathway as potential preventive and therapeutic agents. Med Res Rev. 2012 Jul;32(4):687-726. doi: 10.1002/med.21257. Epub 2012 May 1. PMID: 22549716; PMCID: PMC3393814.
[6]. Oronsky B, Oronsky N, et,al. Episensitization: therapeutic tumor resensitization by epigenetic agents: a review and reassessment. Anticancer Agents Med Chem. 2014;14(8):1121-7. doi: 10.2174/1871520614666140418144610. PMID: 24893730; PMCID: PMC4262965.
[7]. Oronsky B, Scicinski J, et,al. RRx-001, A novel dinitroazetidine radiosensitizer. Invest New Drugs. 2016 Jun;34(3):371-7. doi: 10.1007/s10637-016-0326-y. Epub 2016 Feb 3. PMID: 26841903; PMCID: PMC4859863.
[8]. Jani VP, Asaro R, et,al. RRx-001 Increases Erythrocyte Preferential Adhesion to the Tumor Vasculature. Int J Mol Sci. 2021 Apr 29;22(9):4713. doi: 10.3390/ijms22094713. PMID: 33946824; PMCID: PMC8124275.
[9].Fang J, She J, et,al. RRx-001 Exerts Neuroprotection Against LPS-Induced Microglia Activation and Neuroinflammation Through Disturbing the TLR4 Pathway. Front Pharmacol. 2022 Apr 6;13:889383. doi: 10.3389/fphar.2022.889383. PMID: 35462935; PMCID: PMC9020799.

Cas No.	925206-65-1	SDF
Synonyms	ABDNAZ
Canonical SMILES	BrCC(N1CC([N+]([O-])=O)([N+]([O-])=O)C1)=O
Formula	C₅H₆BrN₃O₅	M.Wt	268.02
Solubility	DMSO : ≥ 100 mg/mL (373.11 mM)	Storage	Store at -20°C
General tips	Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition	Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
		1 mg	5 mg	10 mg
	1 mM	3.7311 mL	18.6553 mL	37.3106 mL
	5 mM	0.7462 mL	3.7311 mL	7.4621 mL
	10 mM	0.3731 mL	1.8655 mL	3.7311 mL

Molarity Calculator
Dilution Calculator

Calculate

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal:μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

Related Products

Reviews

Review for RRx-001

Average Rating: 5 ★★★★★ (Based on Reviews and 19 reference(s) in Google Scholar.)

5 Star

100%

4 Star

0%

3 Star

0%

2 Star

0%

1 Star

0%

Review for RRx-001

GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.

Required fields are marked with *

Overall Rating

★

Review Title

Review

Nickname

Email

You may receive emails regarding this submission. Any emails will include the ability to opt-out of future communications.

RRx-001 (Synonyms: ABDNAZ)

Customer Reviews

GlpBio Citations

Bioactive Compounds Premium Provider