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KZR-504 | Covalent Inhibitor of PSMB9
RATINGS:
Cellular Use: (3 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
PSMB9
  • IC50:51 nM
  • IC50:136 nM
Covalent Inhibitor
300 nM - 1 uM

Selectivity

In Vitro Selectivity Assessment

Potency: IC50 - Beta1, MECL1, Beta2: >250 uM, LMP7, Beta5: >6 uM

Potency Assay Off-Target:
In a MOLT-4 (human T cell leukemia) cellular lysate, a proteasome constitutive/immunoproteasome subu ...
In Cell Selectivity Assessment

Potency: IC50

Potency Assay Off-Target:
Utilizing MOLT-4 (human T cell leukemia) whole (live) cells, a proteasome constitutive/immunoproteas ...

Potency
Cellular
In Vitro

PSMB9

Mode of Action: Covalent Inhibitor

Structure-Activity-Relationship data available? No

In Vivo Validations

Female BALBc mice
Dose: 1 mg/kg and 30 mg/kg
Route of delivery: Intravenous
Organ of interest (O): Blood, Heart, Kidney, Liver, Brain
Target engagement assay: Target inhibition in tissues was measured by ProCISE. In all tissues except brain, a 1 mg/kg dose yielded target inhibition >50%. In brain, a 30 mg/kg dose yielded target inhibition to 40%.

Reference: --

Chemical Information

Molecular Formula C21H23N3O6
SMILEs C[C@]1(C(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CO)NC(=O)c2cccc(=O)[nH]2)CO1
InChI InChI=1S/C21H23N3O6/c1-21(12-30-21)18(27)15(10-13-6-3-2-4-7-13)23-20(29)16(11-25)24-19(28)14-8-5-9-17(26)22-14/h2-9,15-16,25H,10-12H2,1H3,(H,22,26)(H,23,29)(H,24,28)/t15-,16-,21+/m0/s1
Molecular weight 413.16 Da
AlogP -0.4488999999999992
HBond acceptors 9
HBond donors 4
Atoms 53

References

Publications

    Cross References

    canSARChEMBLBindingDB

    Vendors

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    Expert Reviews

    by SERP
    (on 5 Jul 2017 )
    Cellular Use Rating
    In Model Organisms
    The epoxide KZR-504 appears to be a suitable chemical probe of the LMP2 subunit of the immunoproteasome. It is a selective and potent inhibitor, as assessed in the ProCISE platform, which was also used...
    by SERP
    (on 11 Jul 2017 )
    Cellular Use Rating
    In Model Organisms
    KZR-504 is a selective inhibitor of LMP2 and, therefore, of the immunoproteasome. It has been optimized for in vivo use, which has led to some decrease in cellular permeability. Based on the published...
    by SERP
    (on 19 Jul 2017 )
    Cellular Use Rating
    In Model Organisms
    KZR-504 is a potent and highly selective inhibitor for the LMP2 proteosome subunit with ca 50 nM IC50 and >100-fold selectivity over other subunits (80-fold for mouse LMP7) and fair cell permeability...
    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