ISRIB (trans-isomer)

Catalog No.S7400 Batch:S740002

Technical Data

Formula

C₂₂H₂₄Cl₂N₂O₄

Molecular Weight

451.34

CAS No.

1597403-47-8

Solubility (25°C)*

In vitro

DMSO

5 mg/mL (11.07 mM)

Water

Insoluble

Ethanol

Insoluble

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

Clear solution

5% DMSO 1 95% Corn oil

0.1mg/ml

Taking the 1 mL working solution as an example, add 50 μL of 2 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.

* <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

ISRIB (trans-isomer), the trans-isomer of ISRIB, is a potent and selective PERK inhibitor with IC50 of 5 nM and does not have global effects on translation, transcription, or mRNA stability in non-stressed cells.

Targets

PERK ^[1]
(Cell-free assay)

5 nM

In vitro

ISRIB blocks production of endogenous ATF4, whereas XBP1 mRNA splicing and XBP1s production persisted. ISRIB prevents cells from re-establishing ER homeostasis by blocking signaling through the PERK branch of the UPR, and decreases the viability of cells that are subjected to ER-stress. ^[1]

In vivo

ISRIB shows favorable properties in pharmacokinetic profiling experiments and good bioavailability in vivo. ISRIB (0.25 mg/kg i.p.) increases long-term memory in mice by enhancing spatial and fear-associated learning. ^[1]

Protocol (from reference)

Kinase Assay:^{^[1]}	High-content microscopy-based secondary screen ^[1] U2OS cells carrying the ATF4-dGFP-IRES-Cherry reporter are plated in 96 well plates and treated with 100 nM Thapsigargin and 10μM of the cherry-picked compounds for 8 hr. Cells are stained with Hoechst 33,258 and are visualized using an automated microscope. Data acquisition and image analyses are performed with the INCell Developer Toolbox Software, version 1.9. Compounds that block induction of the ATF4-dGFP reporter, do not block the accumulation of mCherry downstream of the IRES, and are deemed non-toxic as determined by cell number measured by counting nuclei, are repurchased for further analyses.
Animal Study:^{^[1]}	Animal Models Male C57BL/6J mice Dosages 0.25 mg/kg Administration i.p.

Kinase Assay:^{^[1]}

High-content microscopy-based secondary screen ^[1]
U2OS cells carrying the ATF4-dGFP-IRES-Cherry reporter are plated in 96 well plates and treated with 100 nM Thapsigargin and 10μM of the cherry-picked compounds for 8 hr. Cells are stained with Hoechst 33,258 and are visualized using an automated microscope. Data acquisition and image analyses are performed with the INCell Developer Toolbox Software, version 1.9. Compounds that block induction of the ATF4-dGFP reporter, do not block the accumulation of mCherry downstream of the IRES, and are deemed non-toxic as determined by cell number measured by counting nuclei, are repurchased for further analyses.

Animal Study:^{^[1]}

Animal Models
Male C57BL/6J mice
Dosages
0.25 mg/kg
Administration
i.p.

References

[1] Sidrauski C, et al. Elife. 2013, 2, e00498.

Customer Product Validation

: Data from [Data independently produced by , , Development, 2017, 144(1):128-138]

Selleck's ISRIB (trans-isomer) has been cited by 7 publications

Neurodegeneration Risk Factor, EIF2AK3 (PERK), Influences Tau Protein Aggregation [ J Biol Chem, 2022, S0021-9258(22)01264-9]	PubMed: 36563857
5-Azacitidine Induces NOXA to Prime AML Cells for Venetoclax-mediated Apoptosis. [ Clin Cancer Res, 2020, 10.1158/1078-0432.CCR-19-1900]	PubMed: 32054729
Intracellular XBP1-IL-24 Axis Dismantles Cytotoxic Unfolded Protein Response in the Liver [ Cell Death Dis, 2020, 6;11(1):17]	PubMed: 31907348
Sphingolipid Modulation Activates Proteostasis Programs to Govern Human Hematopoietic Stem Cell Self-Renewal. [ Cell Stem Cell, 2019, 25(5):639-653]	PubMed: 31631013
Translation repression by maternal RNA binding protein Zar1 is essential for early oogenesis in zebrafish [Miao L, et al. Development, 2017, 144(1):128-138]	PubMed: 27913641
Role of Endoplasmic Reticulum Stress in Learning and Memory Impairment and Alzheimer's Disease-Like Neuropathology in the PS19 and APPSwe Mouse Models of Tauopathy and Amyloidosis [ eNeuro, 2017, 4(4)ENEURO.0025-17.2017]	PubMed: 28721361
Role of Endoplasmic Reticulum Stress in Learning and Memory Impairment and Alzheimer's Disease-Like Neuropathology in the PS19 and APPSwe Mouse Models of Tauopathy and Amyloidosis. [ eNeuro, 2017, 4(4)]	PubMed: 28721361

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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.

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