data + articles · 2 listed
newest 2022spec sheet10 rows
IFB-088 (also called icergustat, related to the tool compound Sephin1) is an experimental small molecule that inhibits the regulatory subunit of protein phosphatase 1 known as PPP1R15A (GADD34). By blocking this subunit it prolongs the cell's integrated stress response, and it has been studied for neurodegenerative and demyelinating conditions such as certain peripheral neuropathies. It is an investigational compound, not an approved drug.
- Selective GADD34 inhibition
- Extends protective stress response
- Studied in neuropathy and demyelination
- Targeted proteostasis mechanism
Mechanism
The integrated stress response works by phosphorylating the translation factor eIF2-alpha, which temporarily slows protein synthesis so a stressed cell can recover; PPP1R15A (GADD34) normally recruits protein phosphatase 1 to reverse this by dephosphorylating eIF2-alpha. IFB-088 selectively inhibits this GADD34-directed dephosphorylation, so eIF2-alpha stays phosphorylated longer and the protective translational slowdown is extended, easing the burden of misfolded proteins in stressed neurons and myelinating cells. This targeted extension of the stress response is the basis for its interest in neurodegeneration and demyelination.
receptor fingerprint
PPP1R15A (GADD34)selective inhibitor
eIF2-alpha phosphorylationindirectly sustained
Safetyrisks and cautions, not medical advice
IFB-088 is an investigational compound whose safety is still being characterized in early studies, so its side-effect profile and interactions in humans are not well established. Manipulating the integrated stress response is a double-edged mechanism, since too much suppression of protein synthesis can itself harm cells, which is one reason such drugs remain experimental. Not medical advice.
Subjective profileweighing the evidence above
Strictly investigational. The integrated stress response is a legitimate target for neuropathy and demyelination, but this is early-stage work, human safety is not characterised, and over-suppressing protein synthesis is a real hazard built into the mechanism. Nothing to act on yet.
Resources
This entry is here for reference.
Research
- 1.Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit.
- 2.Treatment with IFB-088 Improves Neuropathy in CMT1A and CMT1B Mice.
2 listed here; entry last updated July 2026
Reviews
My notesprivate to this device
FAQ
What does IFB-088 target?
It inhibits PPP1R15A (GADD34), the regulatory subunit of protein phosphatase 1 that normally shuts off the integrated stress response.
Why prolong the stress response?
Extending the eIF2-alpha-mediated slowdown of protein synthesis can give stressed neurons and myelinating cells more time to clear misfolded proteins.
Is it an approved medicine?
No; it is an investigational compound still being studied, so its efficacy and safety in people are not established.
Limitations of the evidence
- Unestablished human safety
- Risk from over-suppressing translation
- Unknown interactions
- Investigational status