TTT20171

Protein target name:

SDHC

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

Up to 2 uM

Probe Information

Target and Probe Information

Target Details

Target class:

Other

Define other target class:

Electron Transport Chain

Subclass:

TCA cycle

HUGO ID:

HGNC:10682

Entrez gene ID:

6391

UNIPROT ID:

Q99643

Target alias:

CYB560, CYBL, PGL3, QPS1, SDH3

Probe Details

Chemical Probes Portal ID:

CPP1640

Probe alias:

CID 129009723, 16k

PubChem CID:

129009723

SMILES string:

CCCCCCCCCCCCC(=O)C1=C(C(=C(NC1=O)OC)OC)O

InChi Key:

CZKPAGLXQOQNEI-UHFFFAOYSA-N

Control compound:

(rac)-2,3-dimethoxy-5-(1-methoxyhexyl)pyridin-4-ol (Compound 24)

Physico-chemical properties

Solubility - preferred solvent:

1% DMSO, Water

Solubility - concentration:

30 ug/mL

Potential reactivities:

None known

NMR:

1H NMR (400 MHz, CDCl3): d=0.89 (3 H, t, J=7.0 Hz), 1.25 (m, 18H), 1.68 (m, 2 H), 3.07 (2 H, t, J=7.0 Hz), 3.79 (s, 3H), 4.15 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): d=14.10, 22.67, 24.20, 29.34, 29.42, 29.51, 29.55, 29.64, 29.67, 31.90, 42.55, 57.6361.51, 101.07, 121.25, 155.19, 161.80, 206.42

Storage Recommendations

Storage (dry powder):

0 oC

Storage (solution):

0 oC for up to 24 h

Storage sensitivities:

None known

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

3.3 nM

Potency assay:

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

Structure-activity relationship:

Yes, see ChemMedChem paper

Off target activity

Potency (off target):

IC50

Off target protein and potency:

Mitochondrial Complex I: >10,000 nM

Potency assay (off target):

Spectrophotometric assay in frozen-thawed mouse heart mitochondria.

In cell validation

On target activity in cells

Potency assay (cells):

In 22Rv cells, TTT20171 dose-dependently decreased the oxygen consumption rate, basal respiration, ATP production and decreased maximal respiration.

Toxicity

Cytoxicity assay:

Yes

Notes on cytotoxicity:

Cytotoxicity was assessed by MTT assays in 1 prostate cancer cell line and HEK293 cells (IC50: 22Rv1 cells - 2 ug/mL; HEK293 cells - 28 ug/ml).

Primary Reference

Reference (doi):

10.1002/cmdc.201700196

Reference (PMID):

28523727

Under Review

This probe is in the process of SAB review. Please continue to check back for new reviews and commentary.

SAB Rating

Rating for use in Cells

2 review(s)

Rating for use in Model Organisms

2 review(s)

SAB Members

SAB 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.

Aug 18 2017 - 4:23pm

TTT20171

Probe Information

Target Details

CYB560, CYBL, PGL3, QPS1, SDH3

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Toxicity

Primary Reference

Supporting Organizations

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TTT20171

Probe Information

Target Details

CYB560, CYBL, PGL3, QPS1, SDH3

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Toxicity

Primary Reference

Supporting Organizations

Interested in supporting the portal?