Modification of osimertinib to discover new potent EGFR-TK inhibitors.

The EGFR mutation is a dominant mechanism of acquired resistance after the treatment of non-small cell lung cancer (NSCLC) with osimertinib in clinic. To date, there is no inhibitor approved to overcome the resistance caused by osimertinib. In this study, a series of compounds with phenylamino-pyrimidine scaffold deriving from osimertinib were designed, synthesized and evaluated as fourth-generation EGFR-TK inhibitors.

Design, synthesis and evaluation of new pyrimidine derivatives as EGFR tyrosine kinase inhibitors.

The clinical use of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of non-small cell lung cancer was limited by the drug resistance caused by EGFR mutation. Therefore, in order to overcome the drug resistance, we designed and synthesized a series of 2-aminopyrimidine derivatives as EGFR-TKIs. Among these compounds, compounds A5 and A13 showed significant anti-proliferative activity against the KC-0116 (EGFR) cell line with high selectivity.

Discovery of Potent PROTACs Targeting EGFR Mutants through the Optimization of Covalent EGFR Ligands.

Drug resistance caused by epidermal growth factor receptor (EGFR) mutation has largely limited the clinical use of EGFR tyrosine kinase inhibitors (EGFR-TKIs) for the treatment of non-small-cell lung cancer (NSCLC). Herein, to overcome the intractable problem of drug resistance, proteolysis targeting chimeras (PROTACs) targeting EGFR mutants were developed by optimizing covalent EGFR ligands. Covalent or reversible covalent pyrimidine- or purine-containing PROTACs were designed, synthesized, and evaluated.

The anti-neoplastic activities of aloperine in HeLa cervical cancer cells are associated with inhibition of the IL-6-JAK1-STAT3 feedback loop.

Cervical cancer (CC) is recognized as the most common neoplasm in the female reproductive system worldwide. The lack of chemotherapeutic agents with outstanding effectiveness and safety severely compromises the anti-cipated prognosis of patients. Aloperine (ALO) is a natural quinolizidine alkaloid with marked anti-cancer effects on multiple malignancies as well as favorable activity in relieving inflammation, allergies and infection.

[Phosphate adsorption characteristics onto surface sediments from aquaculture area in Sungo bay].

Phosphate adsorption characteristics onto surface sediments from aquaculture area in Sungo bay were studied in laboratory simulating condition, and phosphate adsorption-desorption equilibrium mass concentration was also analyzed. The results showed that the process of phosphate adsorption onto sediments mainly occurred within 0.5 h, and attended to dynamic equilibrium after 6 h.

[Bioremediation potential of Apostichopus japonicus (Selenka) in coastal bivalve suspension aquaculture system].

Suspension aquaculture of filter-feeding bivalves can produce large amount of faeces and pseudofaeces (biodeposits) that may impact aquaculture environment, while deposit-feeding sea cucumbers may effectively utilize such particulate wastes and act as a scavenger in mariculture system. In this paper, the ingestion, growth, and excretion of deposit-feeder Apostichopus japonicus were investigated in situ seasonally to evaluate its bioremediation potential of a suspension aquaculture system of filter-feeding bivalves. The results showed that A.

[Forms and bioavailability of phosphorus in surface sediments from Sungo Bay].

Unlabelled: Forms and bioavailability of phosphorus in the sediments of eight sampling sites from Sungo Bay were analyzed by means of sequential extraction method (SEDEX).

Results: showed that: (1) The main form of total phosphorus (TP) in sediments was inorganic phosphorus (IP), which accounted for 73.33% and organic phosphorus (OP) was only the minor part.