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KI-696

Inhibitor of KEAP1-NRF2 protein-protein interaction of KEAP1

Structure

Information

  • KEAP1
  • Inhibitor of KEAP1-NRF2 protein-protein interaction
  • Up to 1 uM

In Vitro Validations

Uniprot ID: Q14145
Target Class: Other post-translational modification
Target SubClass: Protein ubiquitination
Potency: Kd
Potency Value: 1.3 nM
Potency Assay: Isothermal Titration Calorimetry (ITC)
PDB ID for probe-target interaction (3D structure): 5fnu
Target aliases:
Kelch-like ECH-associated protein 1, KLHL19, KIAA0 ...

DOI Reference: 10.1021/acs.jmedchem.6b00228

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:
OATP1B1 binding assay IC50 - 2.5 uM; Bile salt export pump - IC50 - 4.0 uM; PDE3A binding assay - IC50 - 10 uM
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SERP ratings and comments

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

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 effects. The in vivo application is hampered by low bioavailability and high clearance, necessitating IV infusions as the mode of administration, which may limit the usefulness of the probe in vivo.

(last updated: 23 Jun 2017 )

SERP Ratings

In Cell Rating

SERP Comments:

Given the labile sulfoxide-N bond, this is likely to be a covalent inhibitor.

(last updated: 7 Aug 2017 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

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, high clearance and lack of oral bioavailability. Having these limitations at hand, it can still be used for in vivo usage upon IV injection at the indicated doses.

(last updated: 16 Nov 2020 )