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.

Adult ; Arsenic ; pharmacology ; Chromosome Aberrations ; chemically induced ; Dose-Response Relationship, Drug ; Female ; Humans ; Lymphocytes ; drug effects ; metabolism ; Male ; Middle Aged

Bronchi ; Child, Preschool ; Diagnostic Errors ; Foreign Bodies ; diagnosis ; Humans ; Lung Diseases ; congenital ; diagnosis ; Male

This study was designed to analyze the effect of the mitochondrial respiratory pathways of Candida albicans (C.albicans) on the biofilm formation.The 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay was used to measure the metabolic activities of biofilms formed by the C.albicans which were cultured in the presence of respiratory pathways inhibitors.The biofilms formed by the wide type (WT),GOA1-deleted (GOA31),GOA1-reconstituted (GOA32),AOX1a-deleted (AOX1) and AOX1b-deleted (AOX2) C.albicans strains were examined by the XTT reduction assay and fluorescence microscopy.The expression of adhesion-related genes BCR1,ALS1,ALS3,ECE1 and HWP1 in the biofilms formed by the above five C.albicans strains was detected by real time polymerase chain reaction.It was found that the metabolic activity of biofilms formed by C.albicans was decreased in the presence of alternative oxidase inhibitor whereas it was increased in the presence of classical mitochondrial respiratory pathway complex Ⅲ or complex Ⅳ inhibitor.AOX1 strain produced scarce biofilms interspersed with few hyphal filaments.Moreover,no significant changes in the expression of BCR1 and ALS3 were observed in the AOX1 strain,but the expression of ALS1 and ECE1 was down-regulated,and that of HWP1 was up-regulated.These results indicate that both AOX1 and AOX2 can promote the biofilm formation.However,AOX1a primarily plays a regulatory role in biofilm formation in the absence of inducers where the promoting effect is mainly achieved by promoting mycelial formation.

In recent years, polysaccharides have received much attention because of their high safety and good immunological activity. The study of polysaccharide in vivo process is a key scientific problem that needs to be solved for polysaccharide drug development. Some progress has been made in the field of polysaccharide pharmacokinetics and immunomodulation. However, due to the lack of both chromogenic and light-absorbing groups and the complex molecular structure of polysaccharides, the in vivo processes and immunomodulatory mechanisms of polysaccharides have been slow to be investigated. The effective combination of multiple techniques can break the bottleneck of difficult tracing and unknown immunomodulatory mechanism of polysaccharides in vivo, and promote the development and utilization of polysaccharides. In this paper, we systematically summarize the key techniques in the study of polysaccharide in vivo processes and immunomodulatory mechanisms in order to provide technical references and research ideas for the study of polysaccharide in vivo processes and immunomodulatory mechanisms.

The aim of the present study was to study the effect of β-estradiol (β-E(2)) on the large-conductance Ca(2+)-activated potassium (BK(Ca)) channel in mesenteric artery smooth muscle cells (SMCs). The mesenteric arteries were obtained from post-menopause female patients with abdominal surgery, and the SMCs were isolated from the arteries using an enzymatic disassociation. According to the sources, the SMCs were divided into non-hypertension (NH) and essential hypertension (EH) groups. Single channel patch clamp technique was used to investigate the effect of β-E(2) and ICI 182780 (a specific blocker of estrogen receptor) on BK(Ca) in the SMCs. The results showed the opening of BK(Ca) in the SMCs was voltage and calcium dependent, and could be blocked by IbTX. β-E(2) (100 μmol/L) significantly increased open probability (Po) of BK(Ca) in both NH and EH groups. After β-E(2) treatment, NH group showed higher Po of BK(Ca) compared with EH group. ICI 182780 could inhibit the activating effect of β-E(2) on BK(Ca) in no matter NH or EH groups. These results suggest β-E(2) activates BK(Ca) in mesenteric artery SMCs from post-menopause women via estrogen receptor, but hypertension may decline the activating effect of β-E(2) on BK(Ca).
Aged ; Estradiol ; analogs & derivatives ; pharmacology ; Female ; Humans ; Hypertension ; physiopathology ; Large-Conductance Calcium-Activated Potassium Channels ; agonists ; metabolism ; physiology ; Mesenteric Arteries ; metabolism ; physiology ; Middle Aged ; Muscle, Smooth, Vascular ; cytology ; metabolism ; physiology ; Patch-Clamp Techniques ; Postmenopause ; physiology ; Receptors, Estrogen ; antagonists & inhibitors

To determine the optimum process conditions for dry granulating technique of Qibai Pingfei granule, granule excipient type, rolling wheel speed and pressure and feeding speed were studied. Taking shaping rate at a time, moisture absorption and dissolubility as index, the type and amount of granule excipient were determined. In addition, taking shaping rate at a time as index, parameters of rolling wheel speed and pressure and feeding speed were researched through single factor test and response surface methodology. The optimum parameters were as follows: lactose as excipient, dry extract powder to excipient at 1:2, rolling wheel speed and pressure at 10.9 Hz and 6.4 MPa and feeding speed at 7.2 Hz. After validation of three batches pilot-scale production, the optimum processing parameters for dry granulating technique of Qibai Pingfei granule is reasonable and feasible, which can provide reliable basis for production.
Drugs, Chinese Herbal ; Powders ; Technology, Pharmaceutical ; methods

Sanjie Zhentong capsules were scanned by using a near infrared spectra probe with different drug mass fraction and the spectral information of capsule shells and contents in it were obtained. Then partial least squares (PLS) models were developed for the prediction of mass fraction of Fritillariae Thunbergii Bulbus and Resine draconis in Sanjie Zhentong capsules. The correlation coefficient (r9c)) and root mean standard error( RMSEC) of 0.949 5, 0.958 2 and 4.742 4, 4.135 7. The models obtained correlation coefficient (r(v)) of 0.919 2, 0.936 7 and root mean square error (RMSECV) of 6.158 9, 5.037 3 respectively in the training set. The paired T test analysis of statistics showed that there were no significant difference between predictive values and measure values. The established models reflected a strong prediction performance and can meet the needs of the production.
Capsules ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Least-Squares Analysis ; Spectroscopy, Near-Infrared ; methods

OBJECTIVETo analyze hepatotoxicity of Polygonum multiflorum and clinical character- istics of drug-induced liver injury (DILI) caused by Polygonum multiflorum and its preparations.

METHODSA retrospective study was performed in 158 patients treated at 302 Military Hospital between January 2009 and January 2014. All of them had used Polygonum multiflorum and its preparations before the onset of DILI, and their clinical characteristics and prognoses were analyzed.

RESULTSOf the 158 DILI patients who used Polygonum multiflorum or its preparations, 92 (58.2%) combined with Western medicine or Chinese herbal preparations without Polygonum multiflorum; 66 patients (41.8%) used Polygonum mult florum and its preparations alone. In 66 DILI patients induced by Polygonum multiflorum or its preparations alone, 51 cases (77.3%) were induced by Polygonum multiflorum compounds and 22.7% by single Po- lygonum multiflorum; 4 cases (6.1%) were caused by crude Polygonum multiflorum and 62 (93.9%) by processed Polygonum multiflorum and its preparations. Clinical injury patterns were hepatocellular 92.4% (61 cases), cholestatic 1.5% (1 case), and mixed 6.1% (4 cases). Pathological examination was per- formed by liver biopsy in 32 cases (48.15%), manifested as hepatocellular degeneration and necrosis, fibroplasia, Kupffer cells with pigment granule, and a large number of eosinophil infiltration, were ob- served. Four patients were developed into liver failure, 4 into cirrhosis, and 1 died.

CONCLUSIONPolygo- num multiflorum and its preparations could induce DILI, but clinical diagnosis of Polygonum multiflorum induced hepatotoxicity should be cautious.

Asian Continental Ancestry Group ; Chemical and Drug Induced Liver Injury ; diagnosis ; Cholestasis ; Drugs, Chinese Herbal ; adverse effects ; Fallopia multiflora ; Humans ; Liver Cirrhosis ; Liver Failure ; Plant Preparations ; adverse effects ; Polygonum ; Retrospective Studies

OBJECTIVETo compare the pharmacokinetic characteristics of brucine following intravenous administration of liposomes, containing total alkaloids from seed of Strychnos nux-vomica, to rats with different phospholipids composition.

METHODLiposomes containing the total alkaloids were prepared by the method of ammonium sulfate transmembrane gradients and stealth liposome technique. The contents of total alkaloids and brucine in liposomes were determined and compared after free drug being removed. After intravenous administration of total alkaloids solution or liposomes with different composition, plasma samples were drawn at predetermined time points and the concentrations of brucine were determined by a validated method of HPLC. Pharmacokinetic analysis was performed by 3P97 program.

RESULTThe ratios of brucine to total alkaloids in liposomes hardly varied with phospholipids composition. Compared with SPC liposome, AUC of brucine was increased 13.3-fold and apparent volume of distribution was decreased to only 3.6% following intravenous administration of HSPC liposome. In addition, besides that AUC of brucine was slightly increased, most pharmacokinetic parameters were not significantly changed after administration of the novel liposome compared with those of SPC liposome.

CONCLUSIONPhospholipids composition has a significant influence on the pharmacokinetics of brucine after intravenous administration of liposomes containing total alkaloids from seed of S. nux-vomica.

Alkaloids ; administration & dosage ; pharmacokinetics ; Animals ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Infusions, Intravenous ; Liposomes ; administration & dosage ; pharmacokinetics ; Male ; Models, Animal ; Rats ; Rats, Sprague-Dawley ; Seeds ; chemistry ; Strychnine ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Strychnos nux-vomica ; chemistry