RUSKI-201

Inhibitor of HHAT

Structure

Information

Protein target names: HHAT

Mechanism of action: Inhibitor

In Vitro Validations

Uniprot ID: Q5VTY9
Target Class: Other post-translational modification
Target SubClass: O-acyltransferase
Potency: 0.2 uM
Potency Value: IC50
Potency Assay: Click-ELISA assay using alkyne-tagged palmitoyl CoA substrate
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Protein-cysteine N-palmitoyltransferase HHAT, SKI1 ...

In Cell Validations

In Vivo Data

No in Vivo Validations

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SERP ratings and comments


SERP Ratings

In Cell Rating

SERP Comments:

Users should note the following limitations: (1) there is still limited SAR reported surrounding the RU-SKI series (e.g., there is no inactive control analog suggested that I am aware of), (2) this series is associated with uncharacterized mechanisms of cytotoxicity, (3) there is limited biophysical data of this chemotype that links direct target engagement in cell-free systems with the reported SAR (e.g., XR, cryo EM, NMR), (4) there is also still limited data showing direct, specific target engagement of this chemotype in cells (e.g., CETSA, pull-downs), and (5) there is limited data describing its cell-free selectivity versus unrelated targets (i.e., selectivity panel). Confidence in this probe could be improved with additional data addressing these aforementioned areas.

Despite this limitations, RU-SKI-201 represents an improvement over the first-generation RU-SKI compounds for Hhat chemical probes and therefore should be used with caution.

Given the historical cytotoxicity of this series and incomplete validation data expected of the highest-quality chemical probes, I would recommend that users of RU-SKI-201 also characterize (1) cellular health (“toxicity”), (2) upstream and downstream pathway targets, and (3) related pathway targets in their particular experimental system to further verify the probe is behaving in a target-based manner rather than through a nonselective or off-target manner.

(last updated: 28 Aug 2020 )

SERP Ratings

In Cell Rating

SERP Comments:

Users of this compound should be aware that this is a diastereoisomeric mixture besides a conformational mixture of E and Z amide. The invitro and in cell data are produced on this mixture.

(last updated: 5 Sept 2020 )

SERP Ratings

In Cell Rating

(last updated: 12 Oct 2020 )