Yao Xue Xue Bao. 2009 Mar; 44(3): 309-13Huan Y, Shen ZFThe aim of this project is to establish a GLP-1 signaling pathway targeted cell model, for screening the new class of GLP-1 receptor agonists as anti-diabetic candidates. Firstly construct a recombined plasmid with multi-copied specific response element (RIP-CRE) regulated by GLP-1 signaling pathway and E-GFP reporter gene. Transient transfect this recombined plasmid into islet cell NIT-1, then detect the responsibility of transfected cell to GLP-1 analogue, Exendin 4. For secondly, use stable transfection and monocloning cell culture to obtain a GLP-1 signaling-specific cell line. It indicates that this cell model can response to Exendin 4, which response can be completely inhibited by GLP-1 receptor antagonist, Exendin 9-39, further showing GLP-1 receptor specific activity with a cAMP-PKA-independently mechanism. Establishment of this novel cell model can be used in high-throughput drug screening of peptides or small molecular GLP-1 analogues.

Yao Xue Xue Bao. 2009 Mar; 44(3): 276-81Guo YS, Guo ZRDrugs designed to act on individual molecular targets usually can not combat multigenic diseases such as cancer, or diseases that affect multiple tissues or cell types such as diabetes. Increasingly, it is being recognised that a balanced modulation of several targets can provide a superior therapeutic effect and side effect profile compared to the action of a selective ligand. The multi-target drugs which impact multiple targets simultaneously are better at controlling complex disease systems and are less prone to drug resistance. Here, we compare the disadvantage of the selective ligands and the predominance of multi-targets drugs in detail and introduce the approaches of designing multiple ligands and the procedure of optimization particularly. A key challenge in the design of multiple ligands is attaining a balanced activity at each target of interest while simultaneously achieving a wider selectivity and a suitable pharmacokinetic profile. On this point, the multi-target approach represents a new challenge for medicinal chemists, pharmacologists, toxicologists, and biochemists.

Yao Xue Xue Bao. 2009 Mar; 44(3): 209-18Guo ZRPhysiology-based and target-based drug discovery constitutes two principal approaches in drug innovation, which are mutually complementary and collaborative. With the target-based approach, a lot of new molecular entities have been marketed as drugs. However, many complicated diseases such as cancer, metabolic disorders, and CNS diseases can not be effectively treated or cured with one medicine acting on a single target. As simultaneous intervention of two (or multiple) targets relevant to a disease has shown improved therapeutic efficacy, the innovation of dual-target drugs has become an active field. Dual-target drug can modulate two receptors, inhibit two enzymes, act on an enzyme and a receptor, or affect an ion channel and a transporter. From viewpoint of molecular design, there are three approaches to construct a dual-target drug molecule. A connective molecule can simply be realized by combining two active molecules or their pharmacophores with a linker; while an integrated molecule comes into an entity either by fusing or by merging the common structural or pharmacophoric features of two active molecules, depending on the extent of the common features. The latter approach facilitates the reduction of molecular size and molecular weight and the optimal overlap between the pharmacodynamic and pharmacokinetic spaces, which will certainly elevate the probability of being a drug.

Zhongguo Zhong Yao Za Zhi. 2009 Feb; 34(3): 255-9Chen D, Peng R, Li L, Sun N, Zhong G, Cai YOBJECTIVE: To study the genetic diversity of Codonopsis tangshen. METHOD: Eighteen germplasmic resources of C. tangshen were analyzed by SRAP and ISSR molecular markers. The systematic diagram of genetic relationship was made by TREECONW software and clustered by UPGMA method. RESULT: Twenty-nine SRAP primer combination amplified 329 bands with 266 (80.85%) polymorphic and 21 ISSR primers amplified 223 bands with 166 (74.44%) polymorphic. The average genetic similarity coefficient was 0.7121 (by SRAPs) and 0.7781 (by ISSRs). Both SRAP and ISSR analyses revealed a high level of genetic diversity in C. tangshen. By cluster analysis, the geographical distribution was not distinctive. The significant positive correlation between SRAPs and ISSRs was observed (r=0.802, P