C3TD879

C3TD879 : Type I inhibitor of CIT

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(2 ratings)

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Probe C3TD879 is in the process of SERP review.

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Information

Type I

up to 1 uM

Probe Availability:

MedChemExpress

In Vitro Validations

Uniprot ID: O14578

Target Class: Kinase

Target SubClass: AGC

Potency: IC50

Potency Value: 12 nM

Potency Assay: Enzymatic assay

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

Target aliases:

Citron Rho-interacting kinase, STK21, KIAA0949, CI ...

DOI Reference: 10.1021/acs.jmedchem.3c01807

Uniprot ID: O14578

Target Class: Kinase

Target SubClass: AGC

Potency: ΔTm

Potency Value: 2.1 Celsius

Potency Assay: Differential scanning fluorimetry (DSF) against untagged, recombinant CITK Kinase Domain purified from either E. coli or Sf9 insect cells

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

Target aliases:

Citron Rho-interacting kinase, STK21, KIAA0949, CI ...

DOI Reference: 10.1021/acs.jmedchem.3c01807

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): C3TD879 for profiling in the Eurofins KinaseProfiler assay against 373 human kinases and found it to have an excellent selectivity profile across the testable kinome, with only 5 kinases showing <50% activity remaining at 1 μM in our initial screen. In follow-up complete IC50 experiments, we demonstrated that C3TD879 has an off-target IC50 < 1 μM for just two human kinases, AAK1 and BIKE. C3TD879 still retains >17-fold selectivity over AAK1 and >75-fold selectivity over BIKE, meaning that in biochemical assays C3TD879 is >17-fold selective for CITK relative to all other tested human kinases.

Potency assay, off target (cells): C3TD879 was profiled in the NCI60 panel to look for evidence of antiproliferative activity across many cancer cell lines. The median GI50 was just 7 μM, with no cell line showing sensitivity to C3TD879 below a concentration of 1 μM.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

(last updated: 5 Mar 2024 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

C3TD879 is a well-characterized selective probe for CITK. As a Type I kinase inhibitor, it binds directly to full-length human CITK in cells (Kd < 10 nM) as measured using a NanoBRET assay. C3TD879 effectively inhibited recombinant CITKKD in a biochemical activity assay, showing an IC50 of 12 nM, and displayed a promising DMPK profile in vitro. The compound's exposure and pharmacokinetic properties were assessed following intravenous and oral administration in rats. To validate data derived from using this probe, it is recommended to use the negative control, C3TD879-N, as suggested in the original study. Although no efficacy data in animal models is available for C3TD879, it serves as a valuable chemical tool for in vitro and cellular experiments to investigate CITK biology.

(last updated: 9 Jul 2024 )