Dataset Information

Properties of FDA-approved small molecule protein kinase inhibitors: A 2022 update.

ABSTRACT: Owing to the dysregulation of protein kinase activity in many diseases including cancer, this enzyme family has become one of the most important drug targets in the 21st century. There are 68 FDA-approved therapeutic agents that target about two dozen different protein kinases and six of these drugs were approved in 2021. Of the approved drugs, twelve target protein-serine/threonine protein kinases, four are directed against dual specificity protein kinases (MEK1/2), thirteen block nonreceptor protein-tyrosine kinases, and 39 target receptor protein-tyrosine kinases. The data indicate that 58 of these drugs are prescribed for the treatment of neoplasms (49 against solid tumors including breast, lung, and colon, five against nonsolid tumors such as leukemias, and four against both solid and nonsolid tumors: acalabrutinib, ibrutinib, imatinib, and midostaurin). Three drugs (baricitinib, tofacitinib, upadacitinib) are used for the treatment of inflammatory diseases including rheumatoid arthritis. Of the 68 approved drugs, eighteen are used in the treatment of multiple diseases. The following six drugs received FDA approval in 2021 for the treatment of these specified diseases: belumosudil (graft vs. host disease), infigratinib (cholangiocarcinomas), mobocertinib and tepotinib (specific forms of non-small cell lung cancer), tivozanib (renal cell carcinoma), and trilaciclib (to decrease chemotherapy-induced myelosuppression). All of the FDA-approved drugs are orally effective with the exception of netarsudil, temsirolimus, and the newly approved trilaciclib. This review summarizes the physicochemical properties of all 68 FDA-approved small molecule protein kinase inhibitors including lipophilic efficiency and ligand efficiency.

SUBMITTER: Roskoski R

PROVIDER: S-EPMC8691985 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundColorectal cancer (CRC) is the third most lethal and malignant type of cancer in the world. Abnormal expression of human microRNA-200a (hsa-miRNA-200a or miR-200a) has previously been characterized as a clinically noticeable biomarker in several cancers, but its role in CRC is still unclear.MethodsThree CRC miRNA expression datasets were integratively analyzed by Least Absolute Shrinkage and Selector Operation (LASSO) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) algorithms. Nine candidate miRNAs were identified and validated for diagnostic and prognostic capability with the prediction model. The potential roles of the tumor suppressor miR-200a-3p in invasion, migration, and epithelial-mesenchymal transition of CRC cells were elaborated by in vitro studies.ResultsNine miRNAs (miR-492, miR-200a, miR-338, miR-29c, miR-101, miR-148a, miR-92a, miR-424, and miR-210) were identified as potentially useful diagnostic biomarkers in the clinic. The overall accuracy rate of the nine miRNAs in the diagnostic model was 0.94, 0.89, and 0.978 in the testing, validation, and independent validation dataset, respectively. CRC patients in the GSE29622 cohort were separated by the prognostic model into the low-risk score group and the high-risk score group. The area under the receiver operating characteristic curve (AUC) was 0.872 and 0.783 for predicting the 1- to 10-year survival of CRC patients. The performance of the prognostic model was validated by an independent TCGA-Colon Adenocarcinoma (COAD) dataset with AUC values between 0.911 and 0.796 in predicting 1- to 10-year survival. Nomograms comprising risk scores, tumor stage, and TNM staging were generated for predicting 1-, 3-, and 5-year overall survival (OS) in the GSE29622 and TCGA-COAD datasets. Colony formation, invasion, and migration in DLD1 and SW480 cells were suppressed by overexpression of miR-200a-3p. Inhibition of miR-200a-3p function contributed to abnormal colony formation, migration, invasion, and epithelial-mesenchymal transition (EMT). miR-200a-3p binding sites were located within the 3'-untranslated region (3'-UTR) of the Forkhead box protein A1 (FOXA1) mRNA.ConclusionWe developed and validated a diagnostic and prognostic prediction model for CRC. miR-200a-3p was determined to be a potential diagnostic and prognostic biomarker for CRC.

Dataset Information

Properties of FDA-approved small molecule protein kinase inhibitors: A 2022 update.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets