- GSK2656157
- GSK2606414
| ISRIB (trans-isomer)PERK inhibitor,potent and selective |
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 = 98.11%
- COA (Certificate Of Analysis)
- HPLC
- NMR (Nuclear Magnetic Resonance)
- MSDS (Material Safety Data Sheet)
- Datasheet
Chemical structure
| Description | ISRIB (trans-isomer), the trans-isomer of ISRIB, is a potent and selective inhibitor of PERK with IC50 of 5 nM. | |||||
| Targets | PERK | |||||
| IC50 | 5 nM | |||||
| Cell experiment [1]: | |
Cell lines | ER-stressed cells |
Preparation method | The solubility of this compound in DMSO is >4.5 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
Reacting condition | 200 nM, 24 hr |
Applications | ISRIB (trans-isomer) inhibited the ATF4-luciferase reporter with the IC50 of 5 nM. ISRIB (200 nM) blocked production of endogenous ATF4 in ER-stressed U2OS cells. ISRIB reduced the viability of cells subjected to PERK-activation by chronic endoplasmic reticulum stress. ISRIB (200 nM) sensitized HEK293T cells to acute ER stress. In Hela cells, ISRIB (25 nM) synergized with ER stress to activate caspase 3/7. In HEK293Trex cells carrying an inducible FLAG epitope-tagged ATF6, ATF6 cleavage was sustained in ER-stressed cells treated with ISRIB. |
| Animal experiment [1]: | |
Animal models | Female CD-1 mice, male C57BL/6J mice |
Dosage form | Intraperitoneal injection, 5 mg/kg |
Application | ISRIB-treated mice displayed significant enhancement in spatial and fear-associated learning. In female CD-1 mice, ISRIB (5 mg/kg) displayed a half-life in plasma of 8 hr and readily crossed the blood-brain barrier, quickly equilibrating with the central nervous system. In male C57BL/6J mice, systemic administration of ISRIB (intraperitoneally, 2.5 mg/kg) enhanced long-term contextual fear memory. ISRIB enhanced auditory fear conditioning in male Sprague Dawley rats. |
Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: [1]. Sidrauski C, Acosta-Alvear D, Khoutorsky A, et al. Pharmacological brake-release of mRNA translation enhances cognitive memory[J]. Elife, 2013, 2: e00498. | |
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| Cas No. | 1597403-47-8 | SDF | Download SDF |
| Chemical Name | N,N"-((1s,4s)-cyclohexane-1,4-diyl)bis(2-(4-chlorophenoxy)acetamide) | ||
| Canonical SMILES | C1CC(CCC1NC(=O)COC2=CC=C(C=C2)Cl)NC(=O)COC3=CC=C(C=C3)Cl | ||
| Formula | C22H24Cl2N2O4 | M.Wt | 451.34 |
| Solubility | ≥8.96 mg/mL in DMSO with gentle warming | 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. | ||
ISRIB (trans-isomer) is a potent inhibitor of the integrated stress response (ISR) [1].
Integrated stress response (ISR) is activated by diverse cellular conditions and rapidly reduces overall protein synthesis while enhancing translation of specific transcripts that support adaptive stress responses. The ISR is mediated by diverse stress-sensing kinases that phosphorylating serine 51 in eukaryotic translation initiation factor alpha (eIF2α) [2].
ISRIB (trans-isomer) is a potent ISR inhibitor. ISRIB reversed the effects of eIF2α phosphorylation with IC50 value of 5 nM. ISRIB inhibited production of endogenous ATF4 (a cAMP element binding transcription factor). In mouse embryonic fibroblasts (MEFs), ISRIB reversed the increase in the 80S monosomes at the expense of polyribosomes induced by endoplasmic reticulum (ER) stress. In ER-stressed cells, ISRIB reduced cell survival [1]. In stressed cells, ISRIB restored mRNA translation and inhibited stress granule (SG) formation induced by eIF2α phosphorylation [2]. ISRIB inhibited the interaction between eIF2B and eIF2 that located at the core of the ISR [3]. Also, ISRIB was an activator of eIF2B and stabilized activated eIF2B dimers [4].
In mice, ISRIB significantly increased hippocampus-dependent spatial and fear-associated learning [1].
References:[1]. Sidrauski C, Acosta-Alvear D, Khoutorsky A, et al. Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife, 2013, 2: e00498.[2]. Sidrauski C, McGeachy AM, Ingolia NT, et al. The small molecule ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly. Elife, 2015, 4.[3]. Sekine Y, Zyryanova A, Crespillo-Casado A, et al. Stress responses. Mutations in a translation initiation factor identify the target of a memory-enhancing compound. Science, 2015, 348(6238): 1027-1030. [4]. Sidrauski C, Tsai JC, Kampmann M, et al. Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response. Elife, 2015, 4: e07314.
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如图，方法是默克给的厂家标准，样品为叔丁醇
现在想把KOH滴定液换成NaOH滴定液，但是领导死活让找依据不然就要做验证
我想知道有没有哪位大神知道这个方法的具体出处。
最好权威一点
