Properties of FDA-approved small molecule protein kinase inhibitors: A 2024 update

Design, Synthesis, and Biological Evaluation of Newly Synthesized Cinnamide-Fluorinated Containing Compounds as Bioactive Anticancer Agents

“…Cancer has remained a critical health issue around the world and is the second fatal cause after cardiovascular diseases. , Protein phosphorylation is among the most abundant and important cellular signaling post-translational modification in the biological system . This reversible enzymatic reaction plays a pivotal role in nearly all signal translational pathways and is carried out by a special class of proteins called protein kinases. , The functional annotation of this phosphorylation process in a growing number of human diseases and physiological conditions underscores the relevance of protein kinases in medicine. , Protein kinases catalyze the phosphorylation of target proteins by transferring the γ-phosphate group of adenosine triphosphate (ATP) onto the side-chain alcohol group of serine, threonine, and tyrosine amino acid residues . Misregulation of protein kinase signaling by kinase hyperactivation or mutation commonly results in human diseases including cancer .…”

“… 6 , 7 Protein kinases catalyze the phosphorylation of target proteins by transferring the γ-phosphate group of adenosine triphosphate (ATP) onto the side-chain alcohol group of serine, threonine, and tyrosine amino acid residues. 8 Misregulation of protein kinase signaling by kinase hyperactivation or mutation commonly results in human diseases including cancer. 9 Therefore, protein kinases are important pharmaceutical targets in cancer treatment.…”

Mirk/Dyrk1B Kinase Inhibitors in Targeted Cancer Therapy

“…During the last years, there has been an increased effort in the discovery of selective and potent inhibitors for targeted cancer therapy, which benefit patients since they provide an improvement in tolerability compared to cytotoxic chemotherapies. The potential benefit of kinase inhibitors in cancer therapy depends on their high selectivity and potency against their targets, as well as on their pharmacokinetic (PK) and pharmacodynamic (PD) properties [ 5 , 6 , 7 , 8 ]. The discovery of oncogenic kinases and the complete mapping of the human kinome has increasingly pushed the research into the development of new anti-cancer drugs.…”

“…Notably, small molecules interacting with protein kinases represent 28% of this total in the major category [ 5 ]. In 2023, there were 72 FDA-approved inhibitors targeting different protein kinases for the treatment of neoplasms (57 against solid tumors such as breast, lung, and colon, 11 against non-solid tumors such as leukemia, and 4 against both solid and non-solid tumors) [ 7 , 8 ].…”

“…Several protein kinase inhibitors that have been approved by the FDA to date target Bcr-Abl kinases in chronic myeloid leukemia; epidermal growth factor receptors (EGFRs) in non-small cell lung and breast cancer; vascular endothelial growth factor receptors (VEGFRs) in renal cell carcinoma and hepatocellular carcinoma; B-Raf (BRAF) kinase in advanced metastatic melanoma; MEK kinases in BRAF V600E mutant metastatic melanoma; anaplastic lymphoma kinase (ALK) in lung adenocarcinoma; Bruton tyrosine kinase (BTK) in B cell malignancies and lymphoma; and JAK2 kinase, phosphoinositide 3-kinase (PI3K), and cyclin-dependent kinases 4/6 (CDK4/6) in metastatic breast cancer [ 6 , 7 , 8 ].…”