scholarly journals Recent Research Progress of Chiral Small Molecular Antitumor-Targeted Drugs Approved by the FDA From 2011 to 2019

2021 ◽  
Vol 11 ◽  
Author(s):  
Xuetong Chu ◽  
Yizhi Bu ◽  
Xiaoping Yang
Keyword(s):  
Small Molecules ◽  
Theoretical Foundation ◽  
Drug Efficacy ◽  
Research Progress ◽  
Antitumor Drugs ◽  
Targeted Drugs ◽  
Chiral Drugs ◽  
Safety And Efficacy ◽  
High Stereoselectivity ◽  
Recent Research Progress

Chiral drugs usually contain chiral centers, which are present as single enantiomers or racemates. Compared with achiral drugs, they have significant advantages in safety and efficacy with high stereoselectivity. Of these drugs, chirality not only exerts influence on the solubility and pharmacokinetic characteristics but also has specific mechanistic characteristics on their targets. We noted that small molecules with unique chiral properties have emerged as novel components of antitumor drugs approved by the FDA in decade. Since approved, these drugs have been continuously explored for new indications, new mechanisms, and novel combinations. In this mini review, recent research progress of twenty-two FDA-approved chiral small molecular-targeted antitumor drugs from 2011 to 2019 is summarized with highlighting the potential and advantages of their applications. We believe that these updated achievements may provide theoretical foundation and stimulate research interests for optimizing drug efficacy, expanding clinical application, overcoming drug resistance, and advancing safety in future clinical administrations of these chiral targeted drugs.

Metabolism and Distribution of Novel Tumor Targeting Drugs In Vivo

2020 ◽  
Vol 21 (13) ◽  
pp. 996-1008
Author(s):  
Mengli Wang ◽  
Qiuzheng Du ◽  
Lihua Zuo ◽  
Peng Xue ◽  
Chao Lan ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Small Molecule ◽  
High Efficiency ◽  
Tumor Therapy ◽  
Research Progress ◽  
Future Research ◽  
Pharmacokinetic Parameters ◽  
Molecular Characteristics ◽  
Targeted Drugs

Background: As a new tumor therapy, targeted therapy is becoming a hot topic due to its high efficiency and low toxicity. Drug effects of targeted tumor drugs are closely related to pharmacokinetics, so it is important to understand their distribution and metabolism in vivo. Methods: A systematic review of the literature on the metabolism and distribution of targeted drugs over the past 20 years was conducted, and the pharmacokinetic parameters of approved targeted drugs were summarized in combination with the FDA's drug instructions. Targeting drugs are divided into two categories: small molecule inhibitors and monoclonal antibodies. Novel targeting drugs and their mechanisms of action, which have been developed in recent years, are summarized. The distribution and metabolic processes of each drug in the human body are reviewed. Results: In this review, we found that the distribution and metabolism of small molecule kinase inhibitors (TKI) and monoclonal antibodies (mAb) showed different characteristics based on the differences of action mechanism and molecular characteristics. TKI absorbed rapidly (Tmax ≈ 1-4 h) and distributed in large amounts (Vd > 100 L). It was mainly oxidized and reduced by cytochrome P450 CYP3A4. However, due to the large molecular diameter, mAb was distributed to tissues slowly, and the volume of distribution was usually very low (Vd < 10 L). It was mainly hydrolyzed and metabolized into peptides and amino acids by protease hydrolysis. In addition, some of the latest drugs are still in clinical trials, and the in vivo process still needs further study. Conclusion: According to the summary of the research progress of the existing targeting drugs, it is found that they have high specificity, but there are still deficiencies in drug resistance and safety. Therefore, the development of safer and more effective targeted drugs is the future research direction. Meanwhile, this study also provides a theoretical basis for clinical accurate drug delivery.

scholarly journals Platform study of genotyping-guided precision medicine for rare solid tumours: a study protocol for a phase II, non-randomised, 18-month, open-label, multiarm, single-centre clinical trial testing the safety and efficacy of multiple Chinese-approved targeted drugs and PD-1 inhibitors in the treatment of metastatic rare tumours

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e044543
Author(s):  
Shuhang Wang ◽  
Hui-Yao Huang ◽  
Dawei Wu ◽  
Hong Fang ◽  
Jianming Ying ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Targeted Therapy ◽  
Single Agent ◽  
Solid Tumours ◽  
Targeted Drugs ◽  
Gene Fusions ◽  
Single Centre ◽  
Open Label ◽  
Safety And Efficacy ◽  
Rare Tumours

IntroductionLimited clinical studies have been conducted on rare solid tumours, and there are few guidelines on the diagnosis and treatment, including experiences with targeted therapy and immunotherapy, of rare solid tumours in China, resulting in limited treatment options and poor outcomes. This study first proposes a definition of rare tumours and is designed to test the preliminary efficacy of targeted and immunotherapy drugs for the treatment of rare tumours.Methods and analysisThis is a phase II, open-label, non-randomised, multiarm, single-centre clinical trial in patients with advanced rare solid tumours who failed standard treatment; the study aims to evaluate the safety and efficacy of targeted drugs in patients with advanced rare solid tumours with corresponding actionable alterations, as well as the safety and efficacy of immune checkpoint (programmed death receptor inhibitor 1, PD-1) inhibitors in patients with advanced rare solid tumours without actionable alterations. Patients with advanced rare tumours who fail standardised treatment and carry actionable alterations (Epidermal growth factor receptor (EGFR) mutations, ALK gene fusions, ROS-1 gene fusions, C-MET gene amplifications/mutations, BRAF mutations, CDKN2A mutations, BRCA1/2 mutations, HER-2 mutations/overexpressions/amplifications or C-KIT mutations) will be enrolled in the targeted therapy arm and be given the corresponding targeted drugs. Patients without actionable alterations will be enrolled in the PD-1 inhibitor arm and be treated with sintilimab. After the patients treated with vemurafenib, niraparib and palbociclib acquire resistance, they will receive combination treatment with sintilimab or atezolizumab. With the use of Simon’s two-stage Minimax design, and the sample size was estimated to be 770. The primary endpoint of this study is the objective response rate. The secondary endpoints are progression-free survival in the targeted treatment group and single-agent immunotherapy group; the duration of response in the targeted therapy and single-agent immunotherapy groups; durable clinical benefit in the single-agent immunotherapy group; and the incidence of adverse events.Ethics and disseminationEthics approval was obtained from the Chinese Academy of Medical Sciences (ID: 20/132-2328). The results from this study will be actively disseminated through manuscript publications and conference presentations.Trial registration numbersNCT04423185; ChiCTR2000039310.

scholarly journals Forensic Entomology in China and Its Challenges

Insects ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 230
Author(s):  
Yu Wang ◽  
Yinghui Wang ◽  
Man Wang ◽  
Wang Xu ◽  
Yanan Zhang ◽  
...  
Keyword(s):  
Species Identification ◽  
Forensic Entomology ◽  
Research Progress ◽  
Temperature Dependent ◽  
Related Research ◽  
Dependent Development ◽  
Faunal Succession ◽  
Recent Research Progress

While the earliest record of forensic entomology originated in China, related research did not start in China until the 1990s. In this paper, we review the recent research progress on the species identification, temperature-dependent development, faunal succession, and entomological toxicology of sarcosaprophagous insects as well as common applications of forensic entomology in China. Furthermore, the difficulties and challenges forensic entomologists face in China are analyzed and possible countermeasures are presented.

Bioapplications of hyperbranched polymers

2015 ◽  
Vol 44 (12) ◽  
pp. 4023-4071 ◽  
Author(s):  
Dali Wang ◽  
Tianyu Zhao ◽  
Xinyuan Zhu ◽  
Deyue Yan ◽  
Wenxin Wang
Keyword(s):  
Biomedical Applications ◽  
Hyperbranched Polymers ◽  
Research Progress ◽  
Recent Research Progress

The recent research progress in biological and biomedical applications of hyperbranched polymers has been summarized in this review.

scholarly journals Supramolecular aggregates as sensory ensembles

2016 ◽  
Vol 52 (88) ◽  
pp. 12929-12939 ◽  
Author(s):  
Qian Wang ◽  
Zhao Li ◽  
Dan-Dan Tao ◽  
Qian Zhang ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Research Progress ◽  
Supramolecular Aggregates ◽  
Supramolecular Aggregation ◽  
Recent Research Progress

Recent research progress in sensing based on induced supramolecular aggregation or disaggregation.

scholarly journals Recent Research Progress in Solar Thermal Conversion Theory and Applications

2015 ◽  
Vol 2015 ◽  
pp. 1-2 ◽  
Author(s):  
Gang Pei ◽  
Yuehong Su ◽  
Sauro Filippeschi ◽  
Hongfei Zheng
Keyword(s):  
Thermal Conversion ◽  
Solar Thermal ◽  
Research Progress ◽  
Recent Research Progress

Electrochemical polymerization for two-dimensional conjugated polymers

2018 ◽  
Vol 6 (40) ◽  
pp. 10672-10686 ◽  
Author(s):  
Qing Zhang ◽  
Huanli Dong ◽  
Wenping Hu
Keyword(s):  
Conjugated Polymers ◽  
Electrochemical Polymerization ◽  
Research Progress ◽  
Future Research ◽  
Special Focus ◽  
Two Dimensional ◽  
Research Directions ◽  
Potential Applications ◽  
Future Research Directions ◽  
Recent Research Progress

This article places special focus on the recent research progress of the EP method in synthesizing CPs. In particular, their potential applications as 2D CPs are summarized, with a basic introduction of the EP method, its use in synthesizing CPs as well as the promising applications of the obtained CPs in different fields. Discussions of current challenges in this field and future research directions are also given.

scholarly journals Emerging Role of Exosomes in Tuberculosis: From Immunity Regulations to Vaccine and Immunotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Yin-Fu Sun ◽  
Jiang Pi ◽  
Jun-Fa Xu
Keyword(s):  
Immune Responses ◽  
Delivery System ◽  
Immune Modulation ◽  
Immune Cell ◽  
Critical Role ◽  
Cell Communication ◽  
Immune Defense ◽  
Research Progress ◽  
Recent Research Progress

Exosomes are cell-derived nanovesicles carrying protein, lipid, and nucleic acid for secreting cells, and act as significant signal transport vectors for cell-cell communication and immune modulation. Immune-cell-derived exosomes have been found to contain molecules involved in immunological pathways, such as MHCII, cytokines, and pathogenic antigens. Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains one of the most fatal infectious diseases. The pathogen for tuberculosis escapes the immune defense and continues to replicate despite rigorous and complicate host cell mechanisms. The infected-cell-derived exosomes under this circumstance are found to trigger different immune responses, such as inflammation, antigen presentation, and activate subsequent pathways, highlighting the critical role of exosomes in anti-MTB immune response. Additionally, as a novel kind of delivery system, exosomes show potential in developing new vaccination and treatment of tuberculosis. We here summarize recent research progress regarding exosomes in the immune environment during MTB infection, and further discuss the potential of exosomes as delivery system for novel anti-MTB vaccines and therapies.

scholarly journals Model of Complexation between C60 Fullerenes and Biologically Active Compounds

2017 ◽  
Vol 12 (2) ◽  
pp. 457-465
Author(s):  
Д.П. Воронин ◽  
D.P. Voronin
Keyword(s):  
Small Molecules ◽  
Discrete Model ◽  
Association Constant ◽  
Equilibrium Constants ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Antitumor Drugs ◽  
Active Compounds ◽  
Self Association ◽  
C60 Fullerenes

Various model approaches for describing the equilibrium complexation of aromatic biologically active compounds with fullerene C60 molecules are proposed. Equilibrium constants of complexation for structurally different biologically active compounds in the aquatic environment were obtained based on these approaches. Models of continuous and discrete aggregation of C60 molecules are proposed, taking into account the polydisperse nature of fullerene solutions. The model of continuous aggregation considers the sequential growth of aggregates upon addition of C60 fullerene monomers to the already existing aggregates, with the equilibrium self-association constant of fullerene KF being the same for all stages of aggregation. The discrete model takes into account the presence of separate stable aggregates and fractal type of the higher aggregates formation from C60 fullerene aggregates. It is achieved by using the simplest two-level hierarchy of clusters distribution in the fractal series 1-4-7-13, known from the literature data. The model of continuous aggregation represents the classical approach used throughout to describe the aggregation of small molecules, while the discrete aggregation model can only be applied to fullerenes. The results obtained in this study lead to the conclusion that fullerene C60 can form stable complexes with aromatic antitumor drugs, which open the possibility of using these substrates in the future in cancer therapy.

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