RRx-001

Catalog No.S8405 Batch:S840501

Technical Data

Formula

C₅H₆BrN₃O₅

Molecular Weight

268.02

CAS No.

925206-65-1

Solubility (25°C)*

In vitro

DMSO

53 mg/mL (197.74 mM)

Ethanol

23 mg/mL (85.81 mM)

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution	5% DMSO 1 95% Corn oil	1.25mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 25 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	2.5mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

RRx-001 is a novel epigenetic modulator with potential radiosensitizing activity. It inhibits glucose 6-phosphate dehydrogenase(G6PD) in human tumor cells, binds hemoglobin and drives RBC-mediated redox reactions under hypoxia. RRx-001 triggers apoptosis and exhibits anticancer activity.RRx-001 is also a downregulator of the CD47- SIRPα checkpoint pathway.

Targets

G6PD ^[1]

Nrf2-ARE ^[3]

In vitro

RRx-001 exerts its anti-proliferative effect, at least partially, through interference with glucose 6 phosphate dehydrogenase (G6PD), a key enzyme in the pentose phosphate pathway, responsible for maintaining adequate levels of the major cellular reductant, NADPH. RRx-001 affects glucose and G6PD enzyme activity in three different cancer cell lines namely Hep G2, CACO-2, and HT-29. RRx-001 induced G6PD inhibition and increased glucose consumption in a concentration dependent fashion. RRx-001 induces p53 and PARP-1 via generation of ROS/RNS. It exerts anticancer activity, at least in part, by interfering with 3 crucial metabolic demands of rapidly proliferating cells: bioenergetics, macromolecular biosynthesis, and manipulation of cellular cytosolic redox homeostasis^[1]. RRx-001 mediates nuclear translocation of Nrf2 and the activation of expression of its downstream enzymes HO-1 and NQO1 in tumor cells. 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. It also triggers p53 and p21 activity in response to double-stranded DNA breaks as well as deregulates cancer cellular energetics and metabolism. RRx-001 is a potent activator of the Nrf2-ARE signaling pathway via ROS/RNS generation^[3].

In vivo

RRx-001 shows promise for short-term blood flow redistribution in tumors with a pericyte- and α-SMA-rich vasculature^[2]. RRx-001 monotherapy is well tolerated, with no dose-limiting toxicities. It not only facilitates nuclear translocation of Nrf2, but also upregulates endogenous Nrf2 expression in SCC VII tumors in mice^[3].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines Human cell cancer lines HEP-G2, HT-29 and CACO-2 Concentrations 5, 50, and 100 μM Incubation Time up to 72 h Method Cell growth and proliferation is assessed using the MTT proliferation assay kit. Briefly, 5×10³ cells are seeded in each well of a 96-well plate and cells are treated with or without compounds. Cells are cultured for up to 72 h. MTT reagent (10 μL) is added to each well, and then incubate for 3 h. Post incubation, the culture medium is removed, 100 μL Crystal Dissolving Solution is added to each well, and the absorbance of the solution is measured at 570 nm. MTT assays for samples of the same conditions are performed in triplicate. Briefly, MTT solution (0.5 mg/mL) is added, cells are incubated at 37ºC for 4 h and absorption at 540 nm is measured using a microplate reader.
Animal Study:^{^[2]}	Animal Models C3H mice/SCID mice Dosages 15 mg/kg Administration i.v.

Cell Assay:^{^[1]}

Cell lines
Human cell cancer lines HEP-G2, HT-29 and CACO-2
Concentrations
5, 50, and 100 μM
Incubation Time
up to 72 h
Method
Cell growth and proliferation is assessed using the MTT proliferation assay kit. Briefly, 5×10³ cells are seeded in each well of a 96-well plate and cells are treated with or without compounds. Cells are cultured for up to 72 h. MTT reagent (10 μL) is added to each well, and then incubate for 3 h. Post incubation, the culture medium is removed, 100 μL Crystal Dissolving Solution is added to each well, and the absorbance of the solution is measured at 570 nm. MTT assays for samples of the same conditions are performed in triplicate. Briefly, MTT solution (0.5 mg/mL) is added, cells are incubated at 37ºC for 4 h and absorption at 540 nm is measured using a microplate reader.

Animal Study:^{^[2]}

Animal Models
C3H mice/SCID mice
Dosages
15 mg/kg
Administration
i.v.

References

Selleck's RRx-001 has been cited by 5 publications

Golgi retention and oncogenic KIT signaling via PLCγ2-PKD2-PI4KIIIβ activation in gastrointestinal stromal tumor cells [ Cell Rep, 2023, 42(9):113035]	PubMed: 37616163
RRx-001 ameliorates inflammatory diseases by acting as a potent covalent NLRP3 inhibitor [ Cell Mol Immunol, 2021, 18(6):1425-1436]	PubMed: 33972740
Integrative analyses of gene expression and chemosensitivity of patient-derived ovarian cancer spheroids link G6PD-driven redox metabolism to cisplatin chemoresistance [ Cancer Lett, 2021, 521:29-38]	PubMed: 34419499
Integrative analyses of gene expression and chemosensitivity of patient-derived ovarian cancer spheroids link G6PD-driven redox metabolism to cisplatin chemoresistance [ Cancer Lett, 2021, 521:29-38]	PubMed: 34419499
Inhibition of the Inflammasome Activity of NLRP3 Attenuates HDM-Induced Allergic Asthma [ Front Immunol, 2021, 12:718779]	PubMed: 34413860

RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.

SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.