Antibody-drug conjugates: Recent advances in linker chemistry

Antibody-drug conjugates (ADCs) are gradually revolutionizing clinical cancer therapy. The antibody-drug conjugate linker molecule determines both the efficacy and the adverse effects, and so has a major influence on the fate of ADCs. An ideal linker should be stable in the circulatory system and release the cytotoxic payload specifically in the tumor. However, existing linkers often release payloads nonspecifically and inevitably lead to off-target toxicity. This defect is becoming an increasingly important factor that restricts the development of ADCs. The pursuit of ADCs with optimal therapeutic windows has resulted in remarkable progress in the discovery and development of novel linkers. The present review summarizes the advance of the chemical trigger, linker‒antibody attachment and linker‒payload attachment over the last 5 years, and describes the ADMET properties of ADCs. This work also helps clarify future developmental directions for the linkers.

AMPA receptor positive modulator, ampakines: research progress / 国际药学研究杂志

Ampakines are a class of pharmacological agents acting as positive modulators of AMPA receptors. Currently, clinical indications studied for ampakines involve many diseases including the respiratory depression and psychoneurosis, etc. The studies using CX516 and CX546 as tool compounds have shown that ampakines could be classified into "high impact ampakines"and "low impact ampakines". The two subclasses of ampakines differ in the chemical structures, influences on receptor dynamics, receptor-ligand bindings, synaptic transmissions, neurotrophin regulations and side effects. According to the available literature, the low impact ampakines have better clinical application prospects than high impact ampakines because of their high safety and good tolerance. The above different characteristics of the two subclasses of ampakines are reviewed in this paper.

Competitiveα-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid receptor antagonists:research advances / 国际药学研究杂志

α-Amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA) receptor, a subtype of ionotropic glutamate receptors widely distributed in the central nervous system, mediates the fast excitatory neurotransmission. Meanwhile more and more evidence indicates that AMPA receptor plays an important role in synaptic plasticity as well as central sensitization, and it also has close relationships with nervous system diseases. Over stimulation of AMPA receptor would produce excitotoxicity, leading to neuronal damage and finally resulting in a multitude of nervous system diseases, such as epilepsy, amyotrophic lateral scelerosis,Parkinson′s dis-ease. Competitive AMPA receptor antagonists that downregulate AMPA receptor′s function are of great importance in the prevention and treatment of nervous system diseases. This article reviews the research advances of competitive AMPA receptor antagonists.

Competitive α-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid receptor antagonists: Research advances / 国际药学研究杂志

α-Amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA) receptor, a subtype of ionotropie glutamate receptors widely distributed in the central nervous system，mediates the fast excitatory neurotransmission. Meanwhile more and more evidence indicates that AMPA receptor plays an important role in synaptic plasticity as well as central sensitization, and it also has close relationships with nervous system diseases. Over stimulation of AMPA receptor would produce excitotoxicity, leading to neuronal damage and finally resulting in a multitude of nervous system diseases，such as epilepsy, amyotrophic lateral scelerosis, Parkinson's dis-ease. Competitive AMPA receptor antagonists that downregulate AMPA receptor's function are of great importance in the prevention and treatment of nervous system diseases. This article reviews the research advances of competitive AMPA receptor antagonists.