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RSL3 | RSL3 : Inhibitor of GPX4
RATINGS:
Cellular Use: (4 reviews)

In Model Organisms: (3 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
GPX4
  • Kd:111 nM
  • EC50:100 nM
Inhibitor
--

Selectivity

In Vitro Selectivity Assessment
Selectivity Assessment Description:
Not available
In Cell Selectivity Assessment
Potency Assay Off-Target:
Chemoproteomic affinity capture with a modified version of RSL3 also bound to SELT and SMG8, but siR ...

Potency
Cellular
In Vitro

GPX4

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? No

In Vivo Validations

Athymic Nude Mice
Dose: 100 mg/kg
Route of delivery: Subcutaneous

Reference: --

Chemical Information

Molecular Formula C23H21ClN2O5
SMILEs COC(=O)c1ccc([C@@H]2c3[nH]c4ccccc4c3C[C@@H](C(=O)OC)N2C(=O)CCl)cc1
InChI InChI=1S/C23H21ClN2O5/c1-30-22(28)14-9-7-13(8-10-14)21-20-16(15-5-3-4-6-17(15)25-20)11-18(23(29)31-2)26(21)19(27)12-24/h3-10,18,21,25H,11-12H2,1-2H3/t18-,21+/m0/s1
Molecular weight 440.11 Da
AlogP 0.0
HBond acceptors 7
HBond donors 1
Atoms 52
PAINS * Yes

* This is an automated alert only, and may not necessarily indicate an issue with this probe. ( Learn more about PAINS )

References

Publications

    Cross References

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    Vendors

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    Expert Reviews

    by SERP
    (on 28 Dec 2016 )
    Cellular Use Rating
    In Model Organisms
    Some intriguing RAS-dependent biology has been uncovered using this probe with respect to its induction of ferroptosis through inhibition of GPX4, which at least in certain contexts was demonstrated...
    by SERP
    (on 6 Apr 2017 )
    Cellular Use Rating
    In Model Organisms
    RSL3 is a ferroptosis inducer that covalently inhibits GPX4. Literature reports claim RSL3 inhibits GPX4 by binding to the catalytic selenocysteine residue, although this has not been directly demonstrated....
    by SERP
    (on 29 Apr 2017 )
    Cellular Use Rating
    ( The reviewer did not leave any comments )
    by SERP
    (on 25 May 2017 )
    Cellular Use Rating
    In Model Organisms
    RSL3 has been demonstrated to induce ferroptosis in certain cellular contexts. The (1S,3R) diastereomer induces ferroptosis, while the (R,R) diasteriomer does not. Chemoproteomic studies show that (an...

    Portal Comments

    A recent publication (DOI: 10.1016/j.redox.2023.102703) reports the small molecule ferroptosis inducer RSL3 not to be a direct inhibitor of GPX4 but of TXNRD1. According to this recent publication, RSL3...

    (last updated: 10 May 2023)

    Note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars. Read more about our evaluation criteria