1417162-36-7

Basic information

• Product Name: RI-2
• Synonyms: RI-2;1-(3,4-Dichlorophenyl)-3-(4-methoxyphenyl)-4-(4-morpholinyl)-1H-pyrrole-2,5-dione
• CAS NO: 1417162-36-7
• Molecular Formula: C₂₁H₁₈Cl₂N₂O₄
• Molecular Weight: 433.28462
• EINECS: -0
• Product Categories: Inhibitors
• Mol File: 1417162-36-7.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 605.6±55.0 °C(Predicted)
• Appearance: /
• Density: 1.441±0.06 g/cm3(Predicted)
• Solubility: ≥21.65 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH
• PKA: -0.77±0.20(Predicted)
• CAS DataBase Reference: RI-2(CAS DataBase Reference)
• NIST Chemistry Reference: RI-2(1417162-36-7)
• EPA Substance Registry System: RI-2(1417162-36-7)

Safety Data

• Hazardous Substances Data: 1417162-36-7(Hazardous Substances Data)

Usage

Description

RI-2 is a reversible inhibitor of RAD51 (IC50 = 44.2 μM), a protein that is central to the homologous recombination process initiated upon DNA double-strand breaks and is often overexpressed in a wide range of human cancer cell types. At 150 μM, it has been shown to inhibit DNA repair and to sensitize cancer cells to cross-linking chemotherapy in vitro.

Uses

RI-2 is a reversible inhibitor of RAD51 (IC50 = 44.2 μM), a protein that is central to the homologous recombination process initiated upon DNA double-strand breaks and is often overexpressed in a wide range of human cancer cell types. At 150 μM, it has been shown to inhibit DNA repair and to sensitize cancer cells to cross-linking chemotherapy in vitro.[Cayman Chemical]

in vitro

although ri-2 did exhibit reduced activity relative to ri-1, it did retain enough activity to sensitize cells to mmc cell-based assays. ri-2 exhibited no reactivity toward glutathione after incubation for 24 hours. rad51 protein that had been treated with ri-2 prior to washing exhibited no measurable loss of dna binding activity, even though ri-2 is known to inhibit rad51 with an ic50 of 44.17 μm. this indicates that rad51 inhibition by ri-2 is fully reversible [1].

in vivo

ri-1, the analogue of ri-2, facilitated mapping of the binding pocket within known crystal structures of rad51. however, this reactivity of ri-1 potentially may limit its development in pre-clinical animal models. ri-1 has been found to exhibit a relatively short half-life, due to reactivity in thiol-containing solutions [1].

IC 50

44.17 μm

references

[1] budke b, kalin jh, pawlowski m, zelivianskaia as, wu m, kozikowski ap, connell pp. an optimized rad51 inhibitor that disrupts homologous recombination without requiring michael acceptor reactivity. j med chem. 2013 jan 10;56(1):254-63.

Upstream product

• 95-76-1 m,p-dichloroaniline 
• 4693-91-8 4-methoxyphenyl-acetic chloride 
• 110-91-8 morpholine 
• 1417162-29-8 3-chloro-1-(3,4-dichloro-phenyl)-4-(4-methoxy-phenyl)-pyrrole-2,5-dione 
• 1417162-23-2 1-(3,4-dichloro-phenyl)-3-hydroxy-4-(4-methoxy-phenyl)-pyrrole-2,5-dione 
• 331274-88-5 N-(3,4-dichloro-phenyl)-2-(4-methoxy-phenyl)-acetamide 
• 104-01-8 4-Methoxyphenylacetic acid 

Relevant articles and documents

METHODS AND COMPOSITIONS INVOLVING RAD51 INHIBITORS

The present invention concerns methods and compositions involving inhibitors and of RAD51, a protein involved in homologous recombination. In some embodiments, there are methods for sensitizing cells to the effects of DNA damaging agents, which can have p