The FDA approved a total of 37 new drugs in 2022, including 22 new molecular entities and 15 new biological products. This is the year with the lowest number of new drugs approved by the FDA since 2017. Among these approved drugs, 21 new drugs belong to the "first-in-class" category, accounting for 56% of the total approved drugs, which is the highest ratio in the past 10 years. Among the drugs approved in 2022, there are 5 small molecule kinase modulators, including the tyrosine kinase 2 (TYK2) allosteric inhibitor deucravacitinib, the first oral pyruvate kinase (PK) activator mitapivat, the Janus kinase 1 (JAK1) selective inhibitor abcrocitinib, the JAK2 selective inhibitor pacritinib and the broad-spectrum fibroblast growth factor receptor (FGFR) inhibitor futibatinib. This review briefly describes the discovery background, research and development process, synthesis routes and clinical efficacy and safety of small molecule kinase modulators approved by the FDA in 2022, hoping to provide ideas and methods for further research on kinase modulators.

Adenocarcinoma, Mucinous ; pathology ; Breast Neoplasms ; pathology ; Carcinoma, Ductal, Breast ; pathology ; Carcinoma, Renal Cell ; pathology ; Carcinoma, Squamous Cell ; pathology ; Cystadenocarcinoma, Mucinous ; pathology ; Cystadenoma, Mucinous ; pathology ; Female ; Giant Cells ; pathology ; Humans ; Osteoclasts ; pathology ; Ovarian Neoplasms ; pathology ; Pancreatic Neoplasms ; pathology ; Thyroid Carcinoma, Anaplastic ; Thyroid Neoplasms ; pathology ; Tongue Neoplasms ; pathology ; Urologic Neoplasms ; pathology

Protein kinases are intimately involved in the pathogenesis of many diseases such as cancer, inflammation, and autoimmune and neurological diseases. Therefore, kinases have been widely studied as drug targets over the past three decades. As of April, 2020, the FDA had approved 59 small molecule kinase inhibitors (SMKIs) in the emerging field of targeted drug therapy. This paper focuses on the biochemistry and pharmacology of these 59 SMKIs and 121 SMKIs for which structures can be retrieved and that are now in phase Ⅱ and Ⅲ clinical trials. In addition, this paper also conducts a simple analysis of several popular targets and their inhibitors.

AlM: To evaluate the clinical effect of 200g/L protein-free calf blood extract eye gel for corneal epithelial defect.METHODS: One hundred and sixty - eight cases of corneal epithelial defect ( 58 cases with herpes simplex keratitis; 24 cases with chemical injury; 85 cases with pterygium operation injury ) were randomly divided into two groups: 84 eyes were treated with protein-free calf blood extract eye gel; 84 cases were treated with basic fibroblast growth factor eye gel ( bFGF ) . The bFGF and protein-free calf blood extract eye gels were used 4 times a day. The treatment course was 7d. Epithelial defect restoration, local symptom and sign were observed.
RESULTS: The difference between pre-treatment and post-treatment was significant ( P<0. 01 ) in the two groups. The effect of protein-free calf blood extract eye gel (83. 3%) group was prior to that of bFGF (69%) for corneal epithelial defect. The effective rate of protein-free calf blood extract eye gel in the herpes simplex keratitis, chemical injury and pterygium operation injury was 72. 4%,69. 2% and 95. 2%. Localized stimulus and adverse reaction of all over the body were not been observed.
CONCLUSlON: Protein-free calf blood extract eye gels is valuable and safe for corneal epithelial defect.

Middle East respiratory syndrome coronavirus (MERS-CoV) has caused outbreaks of SARS-like disease with 35% case-fatality rate, mainly in the Middle East. A more severe outbreak of MERS occurred recently in the Republic of Korea, where 186 people contracted the infections, causing great concern worldwide. So far, there has been no clinically available drug for the treatment of MERS-CoV infection. The potential drugs against MERS-CoV mainly consist of monoclonal antibodies, peptides and small molecular agents. Small molecular agents have an advantage of easier synthesis, lower cost in production and relatively higher stability. There is better chance for those candidates to gain a quick development. This article reviews the progress of developing small molecular MERS-CoV agents.
Antibodies, Monoclonal ; pharmacology ; Antiviral Agents ; pharmacology ; Coronavirus Infections ; drug therapy ; Drug Design ; Humans ; Middle East Respiratory Syndrome Coronavirus ; drug effects

To study the mechanisms of total flavonoid from Glycyrrhizae Radix et Rhizoma (TFGR) and its ingredient isoliquiritigenin (ISL) on their regulation of M2 phenotype polarization of macrophages. IL-4 (60 μg x L(-1)) induced RAW264.7 cells for 6 h to establish the M2 macrophage model. TFGR and ISL restrained breast cancer cells migration with the aid of M2 macrophages in vitro. TFGR and ISL inhibited gene and protein expression of Arg-1, up-regulated gene of HO-1 and protein expression of iNOS, enhanced the expression of microRNA 155 and its target gene SHIP1, meanwhile down-regulated.the phosphorylation of STAT3 and STAT6. So TFGR and ISL were the bioactive fraction and ingredient in Glycyrrhizae Radix et Rhizoma to reverse M2 phenotype macrophages polarization. TFGR and ISL inhibited the promotion of M2 macrophages to breast cancer cells migration in vitro, STAT signal pathways and miR155 were partly involved.
Animals ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Polarity ; drug effects ; Chalcones ; pharmacology ; Flavonoids ; pharmacology ; Glycyrrhiza ; chemistry ; Interleukin-4 ; genetics ; metabolism ; Macrophages ; cytology ; drug effects ; metabolism ; Mice ; RAW 264.7 Cells ; Rhizome ; chemistry

This study was aimed to evaluate the effect of triptolide (TPL) on the reversal of multidrug resistance in K562/A02 cell line. The sensitivity of K562 and K562/A02 to adriamycin (ADM) and reversal of drug resistance were determined with MTT method. The concentration of intracellular ADM and P-glycoprotein expression were detected by flow cytometry. Luciferase reporter gene assay was used to detect the transcriptional activity of MDR1 promoter. The results showed that TPL significantly decreased the resistance degree of K562/A02 cells, inhibited P-glycoprotein expression (mean fluorescent intensity decreased from 123 ± 13 to 39 ± 13) and increased the intracellular concentration of ADM (mean fluorescent intensity increased from 18 ± 5 to 34 ± 6) in K562/A02 cells. Luciferase reporter gene assay demonstrated that TPL inhibited the transcriptional activity of MDR1 promoter by 75%. It is concluded that TPL may effectively reverse the multidrug resistance in K562/A02 cells via modulating P-glycoprotein expression and increasing intracellular ADM accumulation.
ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Diterpenes ; pharmacology ; Doxorubicin ; pharmacology ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Epoxy Compounds ; pharmacology ; Humans ; K562 Cells ; Phenanthrenes ; pharmacology ; Promoter Regions, Genetic

Adult ; Disease Outbreaks ; Humans ; Metapneumovirus ; Paramyxoviridae Infections ; epidemiology ; Respiratory Tract Infections ; epidemiology ; virology ; Students

OBJECTIVETo investigate the effects of the new antiallergic agent N-(pyridin-4-yl)-(indol-3-yl) acetamide-45 (acetamide-45) on electric field stimulation (EFS)-and methacholine-induced contraction of airway smooth muscle in vitro.

METHODSContractions were induced by EFS in isolated trachea and bronchus of rats or by cumulative methacholine concentrations in isolated trachea of guinea pigs. Changes in isometric force of isolated airway smooth muscle were measured by force transducers and recorded on a multi-channel polygraph recorder.

RESULTSAcetamide-45 inhibited the contraction induced by EFS in isolated rat airway. The IC50 was 10.74 (95% CI 8.87-13.00) micromol.L(-1) and 18.83 (95% CI 14.57-24.33) micromol.L(-1) in tracheae and bronchi, respectively. Acetamide-45 also inhibited methacholine-induced contractile response of isolated guinea pig trachea in a concentration-dependent manner. At concentrations of 3, 10, 30 micromol.L(-1) acetamide-45 significantly decreased maximal contractile response of methacholine by 24.6%-43.2% and increased EC50 of methacholine by 3.1-to 21.4-fold.

CONCLUSIONAcetamide-45 inhibits EFS-or methacholine-induced contraction of isolated airway smooth muscle, and these effects might be non-specific inhibition on cholinergic receptor.

Acetamides ; pharmacology ; Animals ; Depression, Chemical ; Electric Stimulation ; Guinea Pigs ; In Vitro Techniques ; Male ; Methacholine Chloride ; pharmacology ; Muscle Contraction ; drug effects ; Muscle, Smooth ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Trachea ; drug effects

Objective:The effect and side effect of the dose-adjusted EPOCH regimen were evaluated perspectively for the pre-liminarily diagnosed angioimmunoblastic T-cell lymphoma. Methods: Nine cases of untreated angioimmunoblastic T-cell lymphoma were diagnosed and enrolled in our department from September 2008 to September 2012. All patients received dose-adjusted EPOCH regimen as first-line chemotherapy. Results: The median age of 9 patients was 54 years. The male-to-female ratio was 2∶1. About 88.9%of all patients were at Ann Arbor stageⅢ/Ⅳ, and 77.8%presented with B symptoms. Anemia was found in 66.7%of 9 patients, and lactate dehydrogenase elevated in 55.6%of patients. After an average of 4.7 cycles of chemotherapy of dose-adjusted EPOCH regi-men, the complete remission rate was 22.2%, and the total response rate was 66.7%. With a median follow-up of 20 months, the 4-year progression-free survival rate was 11.1%, and the overall survival rate was 33.3%. The median survival time was 19 months. The most common adverse events of EPOCH chemotherapy were hematologic toxicity. Grades 3-4 neutropenia and thrombocytopenia were re-ported in 77.8%and 33.3%of patients. Febrile neutropenia was observed in 44.4%of patients. Non-treatment-related mortality was al-so noted. Conclusion: The results of our research showed no clear benefit of treating preliminarily diagnosed angioimmunoblastic T-cell lymphoma with dose-adjusted EPOCH regimen. The main adverse events were hematologic toxicity and could be tolerated.