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.

Synthesis of novel acacetin derivatives and evaluation of their activities / 国际药学研究杂志

Objective To improve the in vivo analgesic activity of acacetin and find leads for the development of new drugs, novel acacetin derivatives containing alkyl amide groups with different length of carbon chain were designed and synthesized according to the molecular structure of the active hit compound found in our previous work. Methods Using apigenin as the initial chemical ma-terial,the acacetin was synthesized through 3 steps,then the target compounds were prepared by conjugating hydroxy group of acace-tin at position 7 with bromoalkyl amides. The analgesic activity of the target compounds was evaluated by acetic acid writhing model of mice. Results and Conclusion Novel acacetin alkyl amide derivatives showed more potent analgesic activities than that of clinical medicine diclofenac,which could be used as leads for further development of new drugs.

Active derivatives based on the resveratrol scaffold:research advances / 国际药学研究杂志

Natural product resveratrol has antioxidation,cardiovascular protection and many other useful biological activities. In recent years,many researchers have paid more and more attention to it. However it cannot be used as candidate for the development of new drug due to its poor druggability. Novel resveratrol derivates with improved water solubility and highly potent biological activity could be obtained by chemical modifying of chemical structure of resveratrol. Researches have shown that resveratrol derivatives exhib?it many kinds of attractive activities,including antitumor,reducing blood fat,antiviral,anti-neurodegenerative diseases and so on, which makes them could be used as leads for the further developing of new drugs. This review discusses the development of novel resve?ratrol derivatives by chemical modification in recent years..

Emergency disposal experience and enlightenment of chemical defense in″Tianjin Port 8·12 Explosion Accident″ / 中国药理学与毒理学杂志

″Tianjin Port 8 · 12 Catastrophic Explosion Accident″ affected the national people′s heart. After the disaster,the chemical defense,medical,explosion and so on various relevant profes?sional experts and rescue teams responded to the national call. Taking the bull by the horns,pooling the wisdom and efforts,the experts and rescue teams carried out and implemented the decision spirit of ″it should not hurt one man,and should not appear serious secondary disasters in the late treat?ment″which put forward by the Party Central Committee and State Council. In order to better learn and sum up experience,the cause of the disaster,the disaster rescue and disposal process,the enlighten?ment brought by the disaster and the recommendations deal with unexpected chemical incidents in the future was discussed in this paper.