Related Experiment Video
Updated: Feb 19, 2026

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach
Published on: February 21, 2019
Design, Synthesis, and Structure-Activity Relationship Studies of 7H‑Pyrrolo[2,3‑d]pyrimidine Derivatives as Potent
Meiying Liu1,2, Yutong Tu3, Wangyang Xu1,2
1School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Abstract:
Casein kinase 1α (CK1α) is a serine/threonine kinase that plays a pivotal role in regulating p53 and other critical signaling pathways and is intimately involved in tumor initiation and progression. Inhibition of CK1α has been demonstrated to be a promising therapeutic strategy for certain types of cancers such as acute myeloid leukemia (AML). In this study, we designed and synthesized a series of novel CK1α inhibitors bearing a 7H-pyrrolo-[2,3-d]-pyrimidine scaffold. The structure-activity relationship was systematically summarized, and notably, compound 7a exhibited potent inhibitory activity against CK1α with an IC50 of 10.96 nM, representing a 9-fold increase in potency as compared to BTX-A51, the only CK1α inhibitor currently in clinical development. Additionally, compound 7a displayed favorable selectivity across a panel of kinases. It also dose-dependently stabilized p53 protein and effectively inhibited the growth of MV4-11 cells. Further optimization of 7a may provide promising CK1α inhibitors with desirable drug-like properties for cancer treatment.
More Related Videos
10:33Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
Published on: October 26, 2015
08:49Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Related Concept Videos
Structure-Activity Relationships and Drug Design
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
Allosteric Proteins-ATCase
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Inhibition of Cdk Activity
Protein Kinases and Phosphatases
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Basicity of Heterocyclic Aromatic Amines