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KI-696 | KI-696 : PPI of KEAP1
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (2 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
KEAP1
  • Kd:1.3 nM
  • EC50:12 nM
PPI
Up to 1 uM

Selectivity

In Vitro Selectivity Assessment
Selectivity Assessment Description:
OATP1B1 binding assay IC50 - 2.5 uM; Bile salt export pump - IC50 - 4.0 uM; PDE3A binding assay - ...

Potency
Cellular
In Vitro

KEAP1

Mode of Action: PPI

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acs.jmedchem.6b00228

In Vivo Validations

Rat
Dose: 35-50 µmol/kg
Route of delivery: Intravenous
Plasma half life: 1.6 h
Systemic clearance: 70 mL/min/kg
Organ of interest (O): Lung
Target engagement assay: KI-696 induces gene expression of NRF2-dependent genes (e.g., Nqo1, HO-1, Txnrd1, Srxn1, Gsta3, Gclc) in the lung.

DOI Reference: 10.1021/acs.jmedchem.6b00228

Chemical Information

Molecular Formula C28H30N4O6S
SMILEs COc1cc([C@@H](CC(=O)O)c2ccc(C)c(CN3C[C@@H](C)Oc4ccccc4S3(=O)=O)c2)cc2nnn(C)c12
InChI InChI=1S/C28H30N4O6S/c1-17-9-10-19(22(14-27(33)34)20-12-23-28(25(13-20)37-4)31(3)30-29-23)11-21(17)16-32-15-18(2)38-24-7-5-6-8-26(24)39(32,35)36/h5-13,18,22H,14-16H2,1-4H3,(H,33,34)/t18-,22+/m1/s1
Molecular weight 550.19 Da
AlogP 3.86372
HBond acceptors 10
HBond donors 1
Atoms 69

Vendors

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Expert Reviews

by SERP
(on 23 Jun 2017 )
Cellular Use Rating
In Model Organisms
KI-696 represents an excellent LMW tool to study the KEAP1-NRF2 interaction in vivo. Discovered by FBS, the probe is well characterised in a number of in vitro assays as well as showing robust in vivo...
by SERP
(on 7 Aug 2017 )
Cellular Use Rating
Given the labile sulfoxide-N bond, this is likely to be a covalent inhibitor.
by SERP
(on 16 Nov 2020 )
Cellular Use Rating
In Model Organisms
This compound has high selectivity and works in low nanomolar range in cells. Thus, it should be a good tool for cell-based interrogations. In vivo, it has pharmacokinetic issues such as short half-life,...
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