The ameliorative effect on chemotherapy-induced injury and tumor immunosuppressive microenvironment of the polysaccharide from the rhizome of Menispermum dauricum DC.

Combined medication has attracted increasing attention as an important treatment option for tumors due to the serious adverse effects of chemotherapy. In this study, as a new therapy strategy, a combination treatment of MDP (a polysaccharide from the rhizome of Menispermum dauricum DC.) with cyclophosphamide (CTX) was investigated.

Development of Hydroxamate Derivatives Containing a Pyrazoline Moiety as APN Inhibitors to Overcome Angiogenesis.

Aminopeptidase N (APN) was closely associated with cancer invasion, metastasis, and angiogenesis. Therefore, APN inhibitors have attracted more and more attention of scientists as antitumor agents. In the current study, we designed, synthesized, and evaluated one new series of pyrazoline-based hydroxamate derivatives as APN inhibitors.

Development of pyrazoline-based derivatives as aminopeptidase N inhibitors to overcome cancer invasion and metastasis.

Aminopeptidase N is considered as a promising anti-tumor target due to its role in tumor invasion, metastasis and angiogenesis. In this report, a new series of pyrazoline-based derivatives were designed, synthesized and evaluated for biological activities. The structure-activity relationships of these pyrazoline-based derivatives were also discussed in detail.

Development of a Bestatin-SAHA Hybrid with Dual Inhibitory Activity against APN and HDAC.

With five histone deacetylase (HDAC) inhibitors approved for cancer treatment, proteolysis-targeting chimeras (PROTACs) for degradation of HDAC are emerging as an alternative strategy for HDAC-targeted therapeutic intervention. Herein, three bestatin-based hydroxamic acids (, and ) were designed, synthesized and biologically evaluated to see if they could work as HDAC degrader by recruiting cellular inhibitor of apoptosis protein 1 (cIAP1) E3 ubiquitin ligase. Among the three compounds, the bestatin-SAHA hybrid exhibited comparable even more potent inhibitory activity against HDAC1, HDAC6 and HDAC8 relative to the approved HDAC inhibitor SAHA.

Design, Synthesis and Biological Evaluation of Novel Osimertinib-Based HDAC and EGFR Dual Inhibitors.

Herein a novel series of histone deacetylases (HDACs) and epidermal growth factor receptor (EGFR) dual inhibitors were designed and synthesized based on the structure of the approved EGFR inhibitor osimertinib (AZD9291). Among them, four compounds , , and exhibited more potent total HDAC inhibition than the approved HDAC inhibitor SAHA. However, these compounds only showed moderate to low inhibitory potency towards EGFR with compounds and possessing IC values against EGFR and EGFRT in the micromolar range.

Leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry. Part II.

Aminopeptidase N (APN) has been proved to be deeply associated with cancer angiogenesis, metastasis and invasion. Therefore, APN gains increasing attention as a promising anti-tumor target. In the current study, we report the design, synthesis, biological evaluation and structure-activity relationship of one new series of leucine ureido derivatives containing the 1,2,3-triazole moiety.

Novel leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry.

The over-expression of aminopeptidase N on diverse malignant cells is associated with the tumor angiogenesis and metastasis. In this report, one new series of leucine ureido derivatives containing the triazole moiety was designed, synthesized and evaluated as APN inhibitors. Among them, compound 13v showed the best APN inhibition with an IC value of 0.

Design, Synthesis, and Biological Evaluation of Pyrazoline-Based Hydroxamic Acid Derivatives as Aminopeptidase N (APN) Inhibitors.

Aminopeptidase N (APN) has been recognized as a target for anticancer treatment due to its overexpression on diverse malignant tumor cells and association with cancer invasion, metastasis and angiogenesis. Herein we describe the synthesis, biological evaluation, and structure-activity relationship study of two new series of pyrazoline analogues as APN inhibitors. Among these compounds, 5-(2-(2-(hydroxyamino)-2-oxoethoxy)phenyl)-3-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamide (compound 13 e) showed the best APN inhibition with an IC value of 0.

Novel leucine ureido derivatives as aminopeptidase N inhibitors. Design, synthesis and activity evaluation.

Aminopeptidase N (APN/CD13) over-expressed on tumor cells and tumor microenvironment, plays critical roles in tumor invasion, metastasis and angiogenesis. Here we described the design, synthesis and preliminary activity studies of novel leucine ureido derivatives as aminopeptidase N (APN/CD13) inhibitors. The results showed that compound 7a had the most potent inhibitory activity against APN with the IC50 value of 20 nM, which could be used for further anticancer agent research.

Rapid screening of aminopeptidase N inhibitors by capillary electrophoresis with electrophoretically mediated microanalysis.

In this work, an electrophoretically mediated microanalysis (EMMA) method with a partial-filling technique was setup to evaluate the inhibitory potency of novel compounds toward aminopeptidase N (APN). It was necessary to optimize the electrophoretic conditions with respect to the kinetic constraints and for attaining high sensitivity. In our setup, a part of the capillary was filled with the incubation buffer for the enzyme reaction, whereas the rest was filled with a suitable BGE for the separation of substrates and products.

Novel β-dicarbonyl derivatives as inhibitors of aminopeptidase N (APN).

Most zinc metalloproteases are over-expressed in tumor cells and play a critical role in the genesis, development, and metastasis of tumors. Novel zinc binding groups (ZBGs) represent a novel strategy to obtain optimal potency and selectivity for zinc metalloproteases inhibitors. Here we described the design, synthesis, and biological studies of novel β-dicarbonyl derivatives as aminopeptidase N (APN/CD13) inhibitors.

Novel leucine ureido derivatives as inhibitors of aminopeptidase N (APN).

Aminopeptidase N (APN/CD13) over expressed on tumor cells, plays a critical role in tumor invasion, metastasis, and tumor angiogenesis. Here we described the design, synthesis and preliminary activity studies of novel leucine ureido derivatives as aminopeptidase N (APN/CD13) inhibitors. The results showed that compound 8c had the most potent inhibitory activity against APN with the IC50 value to 0.

Development of Synthetic Aminopeptidase N/CD13 Inhibitors to Overcome Cancer Metastasis and Angiogenesis.

Cancer metastasis is a major barrier to its treatment and an important cause of patient death. Antimetastatic agents hold promise for patients with advanced metastatic tumors. Aminopeptidase N/CD13 (APN) is being pursued by many as an important target against cancer metastasis and angiogenesis, but there are few reports on the in vivo evaluation of synthetic APN inhibitors.

Selective histone deacetylase inhibitors.

Histone deacetylases (HDACs) are a family of conserved metalloproteases which play a key role in the development of cancer. They can be divided into 18 subtypes according to their structural diversity. Histone deacetylase inhibitors are considered as potential anti-cancer agents and a lot of pan-HDAC inhibitors have entered clinical trials.

Epidermal growth factor receptor as a target for anti-cancer agent design.

The epidermal growth factor (EGF) receptors, one family of protein tyrosine kinases (PTK), are promising targets for the cancer therapy. Many potential inhibitors including monoclonal antibodies (mAbs), reversible inhibitors and irreversible inhibitors have been developed. Some of them have been approved by the FDA or in the stage of clinical trials.