TTT20171

Inhibitor of SDHC

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(2 ratings)

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.

Information

SDHC

Inhibitor

Up to 2 uM

DOI - 10.1002/cmdc.201700196

In Vitro Validations

Uniprot ID: Q99643

Target Class: Other

Target SubClass: TCA cycle

Potency: IC50

Potency Value: 3.3 nM

Potency Assay: Spectrophotometric assay in isolated rat heart mitochondria (rate of succinate-driven coenzyme Q2-linked reduction of DCPIP).

PDB ID for probe-target interaction (3D structure): --

Structure-activity relationship: Yes, see ChemMedChem paper

Target aliases:

Succinate dehydrogenase cytochrome b560 subunit, m ...

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency end-point : IC50 Mitochondrial Complex I: >10,000 nM

Potency assay (off target): Spectrophotometric assay in frozen-thawed mouse heart mitochondria.

I have extra information to add

SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

TTT20171 (compound 16k Wang et al., ChemMedChem 2017) displays nanomolar inhibition of CII but lacks cellular potency. In cell assays, the most sensitive cells (22Rv1 prostate cancer cells) are inhibited at an IC50=5.4 uM, a value well above the suggested use concentration of 2 uM and the criterion of 1 uM for a quality chemical probe. Furthermore, no mechanistic data are provided to demonstrate that the cellular effects are mediated by CII inhibition.

(last updated: 18 Aug 2017 )

SERP Ratings

In Cell Rating

In Model Organisms

(last updated: 11 Nov 2020 )

SERP Ratings

In Cell Rating

SERP Comments:

This work demonstrates a potent in vitro inhibitor of SDH activity against isolated mitochondria (IC50 < 10nM). While cellular anti-proliferative and mitochondrial functional data are presented, there is nothing to link the proposed target engagement with this data. This is particularly concerning as the EC50 for the cell experiments is at least 100x less potent (5.4 uM) than the in vitro biochemical inhibition data (~60 nM). In addition, this inhibitor is only reported for the whole SDH complex, and there is no data to support that the compounds specifically targets the SDHC subunit.

(last updated: 24 Apr 2023 )