| RI-2Optimized reversible RAD51 inhibitor |
Sample solution is provided at 25 µL, 10mM.
Nature.2017 Jan 19;541(7637):417-420.
Nature.2018 Nov;563(7731):407-411.Nature.2018 Jun 13.Nature.2018 Jun 27.Nature.2018 Mar 29;555(7698):673-677.Nature.2017 Sep 7;549(7670):96-100.Nature.2016 Apr 21;532(7599):398-401.
Science.2016 Aug 5;353(6299)594-8Nat Nanotechnol.2017 Dec;12(12):1190-1198.Nature Biotechnology.2017 Jun;35(6):569-576Nat Med.2018 Sep 17.Cell.2018 Dec 21. pii: S0092-8674(18)31561-7.Cell.Available online 25 October 2018.Cell.2018 Sep 27. pii: S0092-8674(18)31183-8.Cell.2018 Jun 28;174(1):172-186.e21.Cell.2018 Feb 22;172(5):1007-1021.e17.Cell.2017 Nov 30;171(6):1284-1300.e21.Cell.2017 Aug 17. pii: S0092-8674(17)30869-3.Cell.2017 Jul 13;170(2):312-323Nat Med.2018 Jan 29.Nat Med.2017 Nov;23(11):1342-1351.Cell.2017 Apr 6;169(2):286-300.Cell.2015 Aug 27;162(5):987-1002.Cell.2015 Feb 12;160(4):729-44.Nature Medicine.2017 Apr;23(4):493-500.Cancer Cell.2018 May 14;33(5):905-921.e5.Cancer Cell.2018 Apr 9;33(4):752-769.e8.Cancer Cell.2018 Mar 12;33(3):401-416.e8.Cancer Cell.2017 Aug 14;32(2):253-267.e5.Nat Methods.2018 Jul;15(7):523-526.Cell Stem Cell.2018 May 3;22(5):769-778.e4.Cell Stem Cell.2017 Nov 20. pii: S1934-5909(17)30375-2.Quality Control & MSDS
- View current batch:
- Purity = 98.00%
- COA (Certificate Of Analysis)
- MSDS (Material Safety Data Sheet)
- Datasheet
Chemical structure
RI-2 Dilution Calculator
calculate
RI-2 Molarity Calculator
calculate
| Cas No. | 1417162-36-7 | SDF | Download SDF |
| Chemical Name | 1-(3,4-dichlorophenyl)-3-(4-methoxyphenyl)-4-morpholino-1H-pyrrole-2,5-dione | ||
| Canonical SMILES | COC1=CC=C(C(C(N2C3=CC(Cl)=C(Cl)C=C3)=O)=C(N4CCOCC4)C2=O)C=C1 | ||
| Formula | C21H18Cl2N2O4 | M.Wt | 433.28 |
| Solubility | ≥21.65mg/mL in DMSO | Storage | Store at -20°C |
| Physical Appearance | A solid | Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request |
| 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. | ||
Description:
IC50: 44.17 μM
Homologous recombination (HR) is an essential process in cells that provides repair of DNA double-strand breaks and lesions that block DNA replication. RAD51 is an evolutionarily conserved protein that is central to HR. Overexpression of RAD51 protein is common in cancer cells and represents a potential therapeutic target in oncology. RI-2 is an optimized reversible RAD51 inhibitor.
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].
Clinical trial: Up to now, RI-2 is still in the preclinical development stage.
Reference:[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.
