Proteins are the main targets of most drugs; however, system-wide methods to monitor
protein activity and function are still underused in drug discovery. Novel biochemical …

Targeted covalent inhibitors (TCIs) are designed to bind poorly conserved amino acids by
means of reactive groups, the so-called warheads. Currently, targeting noncatalytic cysteine …

Receptor tyrosine kinase signalling pathways have been successfully targeted to inhibit
proliferation and angiogenesis for cancer therapy. However, kinase deregulation has been …

INTRODUCTION Molecularly targeted drugs such as imatinib and crizotinib have
revolutionized the treatment of certain blood and lung cancers because of their remarkable …

Medicinal chemistry has discovered thousands of potent protein and lipid kinase inhibitors.
These may be developed into therapeutic drugs or chemical probes to study kinase biology …

Abstract Cyclin-dependent kinase 9 (CDK9), an important regulator of transcriptional
elongation, is a promising target for cancer therapy, particularly for cancers driven by …

Heterobifunctional molecules that recruit E3 ubiquitin ligases, such as cereblon, for targeted
protein degradation represent an emerging pharmacological strategy. A major unanswered …

Therapeutically targeting aberrant intracellular kinase signaling is attractive from a biological
perspective but drug development is often hindered by toxicities and inadequate efficacy …

Summary p97 is a AAA-ATPase with multiple cellular functions, one of which is critical
regulation of protein homeostasis pathways. We describe the characterization of CB-5083, a …

Protein kinases comprise a large family of structurally related enzymes. A major goal in
kinase-inhibitor development is to selectively engage the desired kinase while avoiding …