6Z84

CK2 alpha bound to chemical probe SGC-CK2-1 derivative

This is a non-PDB format compatible entry.

Summary for 6Z84

• Entry DOI: 10.2210/pdb6z84/pdb
• Descriptor: Casein kinase II subunit alpha, SULFATE ION, ~{N}-[1-[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]indol-6-yl]ethanamide, ... (4 entities in total)
• Functional Keywords: kinase, inhibitor, chemical probe, structural genomics, structural genomics consortium, sgc, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 82551.50

Authors

Kraemer, A.,Wells, C.,Drewry, D.H.,Pickett, J.E.,Axtman, A.D.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2020-06-02, release date: 2020-07-29, Last modification date: 2024-01-24)

Primary citation

Wells, C.I.,Drewry, D.H.,Pickett, J.E.,Tjaden, A.,Kramer, A.,Muller, S.,Gyenis, L.,Menyhart, D.,Litchfield, D.W.,Knapp, S.,Axtman, A.D.
Development of a potent and selective chemical probe for the pleiotropic kinase CK2.
Cell Chem Biol, 28:546-558.e10, 2021

PubMed Abstract: Building on the pyrazolopyrimidine CK2 (casein kinase 2) inhibitor scaffold, we designed a small targeted library. Through comprehensive evaluation of inhibitor selectivity, we identified inhibitor 24 (SGC-CK2-1) as a highly potent and cell-active CK2 chemical probe with exclusive selectivity for both human CK2 isoforms. Remarkably, despite years of research pointing to CK2 as a key driver in cancer, our chemical probe did not elicit a broad antiproliferative phenotype in >90% of >140 cell lines when tested in dose-response. While many publications have reported CK2 functions, CK2 biology is complex and an available high-quality chemical tool such as SGC-CK2-1 will be indispensable in deciphering the relationships between CK2 function and phenotypes.

PubMed: 33484635
DOI: 10.1016/j.chembiol.2020.12.013

Experimental method

X-RAY DIFFRACTION (2.5 Å)