Chemical Probes logo

SGC-CK1γ-1

SGC-CK1γ-1 : Inhibitor of CSNK1G1, CSNK1G2, CSNK1G3

Structure

Information

  • CSNK1G1
  • CSNK1G2
  • CSNK1G3
  • Inhibitor

In Vitro Validations

Uniprot ID: Q9HCP0
Target Class: Kinase
Target SubClass: CK1
Potency: IC50
Potency Value: 28 nM
Potency Assay: Enzymatic assay
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Casein kinase I isoform gamma-1, CSNK1G1, KC1G1_HU ...

DOI Reference: 10.1021/acs.jmedchem.5c02609

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay, off target (cells): Selectivity was assessed in a panel of 192 kinases via a NanoBRET assay selectivity panel (K192) at a fixed concentration of 1 μM.
Probe Selectivity in Cell:
SGC-CK1γ-1 demonstrated excellent selectivity across three biological replicates of K192 assays. The only kinase with greater than 30% fractional occupancy at 1 μM was CK1γ2 (74%) ( CK1γ2 being the sole representative from the CK1γ subfamily in the K192 panel).
Potency assay, off target (cells): SGC-CK1γ-1 was screened in a larger NanoBRET panel of 240 kinases (K240). Cpd 14 maintained strong in-cell selectivity with only two kinases demonstrating greater than 30% fractional occupancy: MOK (37%) and CK1γ2 (66%). Screening of 14 against MOK in a NanoBRET assay with an 11-point dose–response format revealed that the IC50 is greater than 5 μM; therefore, MOK is not a significant off-target of 14. The IC50 of 14 in the CK1γ2 NanoBRET assay with tracer K10, the same tracer used in the K192 and K240 panels, was previously determined to be 140 nM
Potency assay, off target (cells): <ultiplexed inhibitor bead and mass spectrometry (MIB/MS) screen was used to further assed Cpd 14.
Probe Selectivity in Cell:
Cumulatively, across both the MIB/MS and K240, it was possible to assess the binding of SGC-CK1γ-1 to 372 kinases, 145 of which were screened in both assay formats. Using this dual profiling approach, cpd 14 was found to be the optimal candidate for designation as a CK1γ chemical probe for all three CK1γ proteins: CK1γ1, CK1γ2, and CK1γ3.
I have extra information to add

SERP ratings and comments

No SERP comments found for SGC-CK1γ-1