RI-1

RAD51 inhibitor,cell-permeable CAS# 415713-60-9

RI-1

Catalog No. BCC1896----Order now to get a substantial discount!

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Chemical structure

RI-1

3D structure

Chemical Properties of RI-1

Cas No. 415713-60-9 SDF Download SDF
PubChem ID 1074953 Appearance Powder
Formula C14H11Cl3N2O3 M.Wt 361.61
Type of Compound N/A Storage Desiccate at -20°C
Solubility DMSO : 33.33 mg/mL (92.17 mM; Need ultrasonic)
H2O : < 0.1 mg/mL (insoluble)
Chemical Name 3-chloro-1-(3,4-dichlorophenyl)-4-morpholin-4-ylpyrrole-2,5-dione
SMILES C1COCCN1C2=C(C(=O)N(C2=O)C3=CC(=C(C=C3)Cl)Cl)Cl
Standard InChIKey MWSUIZKGNWELRF-UHFFFAOYSA-N
Standard InChI InChI=1S/C14H11Cl3N2O3/c15-9-2-1-8(7-10(9)16)19-13(20)11(17)12(14(19)21)18-3-5-22-6-4-18/h1-2,7H,3-6H2
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of RI-1

DescriptionRI-1 is a cell-permeable inhibitor of RAD51.
TargetsRAD51    

RI-1 Dilution Calculator

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RI-1 Molarity Calculator

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Preparing Stock Solutions of RI-1

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.7654 mL 13.8271 mL 27.6541 mL 55.3082 mL 69.1353 mL
5 mM 0.5531 mL 2.7654 mL 5.5308 mL 11.0616 mL 13.8271 mL
10 mM 0.2765 mL 1.3827 mL 2.7654 mL 5.5308 mL 6.9135 mL
50 mM 0.0553 mL 0.2765 mL 0.5531 mL 1.1062 mL 1.3827 mL
100 mM 0.0277 mL 0.1383 mL 0.2765 mL 0.5531 mL 0.6914 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

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Background on RI-1

RI-1 Description:IC50: 5~30 μM [1]
RAD51 is a eukaryote gene, encoding RAD51 protein that participates in DNA damage induction and complex signal pathway of cell cycle checkpoint of homologous recombination in cells. RI-1 inhibits the over-expression of RAD51 in cancer cells by bonding covalently to the surface of RAD51 protein at Cys 319 and irreversibly loosen a protein-protein interface that is essential for filament formation and recombinase activity.
In vitro: RI-1 binds covalently to the surface of RAD51 protein at cysteine 319 that likely destabilizes an interface used by RAD51 monomers to oligomerize into filaments on DNA. Correspondingly, the molecule inhibits the formation of subnuclear RAD51 foci in cells following DNA damage, while leaving replication protein A focus formation unaffected. Finally, it potentiates the lethal effects of a DNA cross-linking drug in human cells. Given that this inhibitory activity is seen in multiple human tumor cell lines, RI-1 holds promise as an oncologic drug [1].
In vivo: There are limits to the development of RI-1 in pre-clinical in vivo models due to its short half-life in tissue culture media and aqueous buffers. RI-2, a homolog of RI-1, was created that mitigated these effects(119). RI-2 was shown to bind Rad51 and inhibit the nuclear foci of Rad51 at sites of DNA damage. RI-2 is currently the subject of further in vitro and in vivo studies and is being used to identify third generation analogs that inhibit the function of Rad51 [2].
Clinical trial: Up to now, RI-1 is still in the preclinical development stage.
Reference:
[1] Budke B, Logan HL, Kalin JH, Zelivianskaia AS, Cameron McGuire W, Miller LL, Stark JM, Kozikowski AP, Bishop DK, Connell PP. RI-1: a chemical inhibitor of RAD51 that disrupts homologous recombination in human cells. Nucleic Acids Res. 2012;40(15):7347-57.
[2] Christian Jekimovs, Emma Bolderson, Amila Suraweera, Mark Adams, Kenneth J. O’Byrne, and Derek J. Richard. Chemotherapeutic Compounds Targeting the DNA Double-Strand Break Repair Pathways: The Good, the Bad, and the Promising. Front Oncol. 2014; 4: 86.

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References on RI-1

RI-1: a chemical inhibitor of RAD51 that disrupts homologous recombination in human cells.[Pubmed:22573178]

Nucleic Acids Res. 2012 Aug;40(15):7347-57.

Homologous recombination serves multiple roles in DNA repair that are essential for maintaining genomic stability. We here describe RI-1, a small molecule that inhibits the central recombination protein RAD51. RI-1 specifically reduces gene conversion in human cells while stimulating single strand annealing. RI-1 binds covalently to the surface of RAD51 protein at cysteine 319 that likely destabilizes an interface used by RAD51 monomers to oligomerize into filaments on DNA. Correspondingly, the molecule inhibits the formation of subnuclear RAD51 foci in cells following DNA damage, while leaving replication protein A focus formation unaffected. Finally, it potentiates the lethal effects of a DNA cross-linking drug in human cells. Given that this inhibitory activity is seen in multiple human tumor cell lines, RI-1 holds promise as an oncologic drug. Furthermore, RI-1 represents a unique tool to dissect the network of reaction pathways that contribute to DNA repair in cells.

Immunogenicity and immunomodulatory activity of bovine surfactant (SF-RI 1).[Pubmed:1498502]

Acta Paediatr. 1992 May;81(5):383-8.

Respiratory distress syndrome in preterm infants can be treated successfully by endotracheal administration of a bovine surfactant preparation (SF-RI 1). Before the routine use of xenogenic surfactant preparations can be recommended, their immunogenicity as well as their in-vivo and in-vitro immunomodulatory activity have to be investigated. High titers of anti-surfactant antibodies were detected by a sensitive ELISA after immunizing rats, rabbits and mice with SF-RI 1. Repeated endotracheal administration of SF-RI 1 resulted in a humoral antibody response in three out of eight rabbits. After treatment of 34 preterm infants with SF-RI 1 (50-200 mg/kg), a humoral immune response to SF-RI 1 could not be detected. In-vitro restimulation of peripheral blood lymphocytes with SF-RI 1 after primary in-vivo administration did not result in cell proliferation as measured by 3H-thymidine incorporation. SF-RI 1 did not stimulate peripheral blood lymphocytes of neonates in vitro. The mitogenic response of these cells to stimulation with PHA, ConA or PWM was heavily impaired in the presence of SF-RI 1 concentrations increasing from 0.04 to 4 mg/ml. These data indicate that SF-RI 1 is immunogenic and that it may have an influence on lymphocyte proliferation in vivo.

A role for accessory genes rI.-1 and rI.1 in the regulation of lysis inhibition by bacteriophage T4.[Pubmed:20945083]

Virus Genes. 2010 Dec;41(3):459-68.

Lysis inhibition (LIN) is a known feature of the T-even family of bacteriophages. Despite its historical role in the development of modern molecular genetics, many aspects of this phenomenon remain mostly unexplained. The key element of LIN is an interaction between two phage-encoded proteins, the T holin and the RI antiholin. This interaction is stabilized by RIII. In this report, we demonstrate the results of genetic experiments which suggest a synergistic action of two accessory proteins of bacteriophage T4, RI.-1, and RI.1 with RIII in the regulation of LIN.

Description

RI-1 is a RAD51 inhibitor with IC50 ranging from 5 to 30 μM.

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