ISRIB (trans-isoMer)

Base Information

• Chemical Name: ISRIB (trans-isoMer)
• CAS No.: 1597403-47-8
• Molecular Formula: C₂₂H₂₄Cl₂N₂O₄
• Molecular Weight: 451.35
• DSSTox Substance ID: DTXSID601045380
• Nikkaji Number: J3.449.837G,J3.449.838E
• Wikipedia: ISRIB
• Wikidata: Q15409421
• ChEMBL ID: CHEMBL4303573
• Mol file: 1597403-47-8.mol

Synonyms:ISRIB (trans-isoMer);trans-N,N'-(cyclohexane-1,4-diyl)bis(2-(4-chlorophenoxy)acetamide);N,N'-((1r,4r)-cyclohexane-1,4-diyl)bis(2-(4-chlorophenoxy)acetamide) ISRIB(trans-isomer);Trans-ISRIB;Acetamide, N,N'-trans-1,4-cyclohexanediylbis[2-(4-chlorophenoxy)-

Chemical Property of ISRIB (trans-isoMer)

Chemical Property:

• Boiling Point: 719.0±60.0 °C(Predicted)
• PKA: 13.63±0.40(Predicted)
• PSA: 76.66000
• Density: 1.33±0.1 g/cm3(Predicted)
• LogP: 4.77660
• Storage Temp.: 2-8°C
• Solubility.: insoluble in EtOH; insoluble in H2O; insoluble in EtOH; ≥8.96 mg/mL in DMSO with gentle warming
• XLogP3: 4.8
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 8
• Exact Mass: 450.1113126
• Heavy Atom Count: 30
• Complexity: 493

Purity/Quality:

99% ^*data from raw suppliers

trans-ISRIB ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1CC(CCC1NC(=O)COC2=CC=C(C=C2)Cl)NC(=O)COC3=CC=C(C=C3)Cl
• 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.
• Uses: trans-ISRIB is an integrated stress response (ISR) inhibitor; reverses the effects of eIF2α phosphorylation (IC50 = 5 nM) and restores cell translation capacity. Acts downstream of PERK, targeting interactions between eIF2α kinases and elF2B. Blocks ATF4 production without altering the IRE1 or ATF6 responses in vitro. Displays memory enhancement in hippocampus-dependent spatial and fear-associated learning in rodents. trans-ISRIB promotes survival of pluripotent stem cells in culture when used in combination with Chroman-1, emricasan, and polyamines, a combination known as CEPT. When used as part of the CEPT cocktail, trans-ISRIB improves survival of differentiated cells following cryopreservation. Brain penetrant. ISRIB (integrated stress response inhibitor) has been used as an inhibitor of integrated stress response.
• Biological Functions: ISRIB (trans-isomer) is a potent inhibitor of the integrated stress response (ISR).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).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. In stressed cells, ISRIB restored mRNA translation and inhibited stress granule (SG) formation induced by eIF2α phosphorylation. ISRIB inhibited the interaction between eIF2B and eIF2 that located at the core of the ISR. Also, ISRIB was an activator of eIF2B and stabilized activated eIF2B dimers.In mice, ISRIB significantly increased hippocampus-dependent spatial and fear-associated learning.

Technology Process of ISRIB (trans-isoMer)

There total 2 articles about ISRIB (trans-isoMer) which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 71.0%

cis-1,4-cyclohexanediamine (15827-56-2) + 4-chlorophenyloxyacetyl chloride (4122-68-3) → 2-(4-chlorophenoxy)-N-[(1s,4s)-4-[2-(4-chlorophenoxy)acetamido]cyclohexyl]acetamide (548470-11-7,1597403-47-8,1597403-48-9)

Guidance literature:

With potassium carbonate; In tetrahydrofuran; water; at 20 ℃; for 1.5h;

Reference yield: 65.0%

trans-1,4-cyclohexyldiamine (2615-25-0) + 4-chlorophenyloxyacetyl chloride (4122-68-3) → 2-(4-chlorophenoxy)-N-[(1r,4r)-4-[2-(4-chlorophenoxy)acetamido]cyclohexyl]acetamide (548470-11-7,1597403-47-8,1597403-48-9)

Guidance literature:

With potassium carbonate; In tetrahydrofuran; water; at 20 ℃; for 0.5h;

upstream raw materials:

trans-1,4-cyclohexyldiamine

4-chlorophenyloxyacetyl chloride

cis-1,4-cyclohexanediamine

Refernces