A guide to selecting high-performing antibodies for CSNK1A1 (UniProt ID: P48729) for use in western blot, immunoprecipitation, and immunofluorescence.

Read more about A guide to selecting high-performing antibodies for CSNK1A1 (UniProt ID: P48729) for use in western blot, immunoprecipitation, and immunofluorescence.

Structure-guided optimization of small molecules targeting Yck2 as a strategy to combat Candida albicans.

Read more about Structure-guided optimization of small molecules targeting Yck2 as a strategy to combat Candida albicans.

Chemoproteomic Profiling of C. albicans for Characterization of Antifungal Kinase Inhibitors.

Read more about Chemoproteomic Profiling of C. albicans for Characterization of Antifungal Kinase Inhibitors.

UNC9630 A chemical handle for FBXO22.

overview
in vitro potency
cell based assay data

overview

SGC in collaboration with Lindsey James’ lab at the University of North Carolina at Chapel Hill (UNC) has developed a chemical handle, UNC9630, for FBXO22.

This followed from the development of degraders of NSD2 (UNC8732) using the NSD2 PWWP1 ligand UNC6934, and the discovery of the mechanism of action via FBXO22.

In cells, the primary amine is converted to the aldehyde which forms a covalent adduct with FBXO22 C326. For in vitro (cell-free) studies, the bisulfite adduct UNC10089 can be used as a prodrug for the aldehyde. The methylated secondary amine UNC9631 cannot be oxidized to the aldehyde and is a negative control.

properties

selectivity profile

in vitro potency

cell based assay data

In cells, the primary amine is converted to the aldehyde which forms a covalent adduct with FBXO22 C326.

references

pk properties

co-crystal structures

synthetic schemes

materials and methods

SGC-NSP2PRO-1 a chemical probe for CHIKV nsp2 protease

Aliquots of the probe and control are available under a click-trust agreement.

overview
selectivity profile
in vitro potency
cell based assay data
references

overview

SGC-UNC has developed a potent (IC₅₀ 40 nM), selective and cell active inhibitor of CHIKV nsp2 protease (SGC-NSP2PRO-1). Vinyl sulfone SGC-NSP2PRO-1 was identified as a potent inhibitor of the nsP2 cysteine protease (nsP2pro) that reduced viral titer against infectious isolates of Chikungunya and other alphaviruses.

A negative control was obtained by alkylating the amide NH with an isopropyl group to give SGC-NSP2PRO-1N which is relatively inactive (IC₅₀ >10 mM) compared to the probe in the protease inhibition assay.

properties

selectivity profile

SGC-NSP2PRO-1 was tested against numerous cysteine proteases and found to be highly selective for CHIKV nsp2 protease.

in vitro potency

The covalent nature of the inhibitor was established via kinetic analysis, showing time-dependent inhibition with k_inact/K_i = 5950 M^-1s^-1.

The position of covalent modification was established as Cys478 following mass spectral analysis of the peptides derived by trypsin digest after chemical probe treatment.

cell based assay data

SGC-NSP2PRO-1 potently inhibited the proliferation of the CHIKV virus using a luciferase reporter assay with EC₅₀ of 50 nM. SGC-NSP2PRO-1N was inactive in this assay.

references

Anirban Ghoshal, Edwin G. Tse, Mohammad Anwar Hossain, Kesatebrhan Haile Asressu, Eric M. Merten, John D. Sears, Stefanie Howell, Sumera Perveen, Jane Burdick,, Noah L. Morales, Sabian A. Martinez, Isabella Law, Bennett J. Davenport, Thomas E. Morrison, Zachary J. Streblow, Daniel N. Streblow, Angie L. Mordant, Thomas S. Webb, Aurora Cabrera, Laura E. Herring, Cheryl H. Arrowsmith, Kenneth H. Pearce, Nathaniel J. Moorman, Mark T. Heise, Rafael M. Couñago, Peter J. Brown and Timothy M. Willson.

A covalent chemical probe for Chikungunya nsP2 cysteine protease with antialphaviral activity and proteome-wide selectivity. Sci Rep 15, 7264 (2025). https://doi.org/10.1038/s41598-025-91673-x