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排序方式: 共有10000条查询结果,搜索用时 187 毫秒
891.
892.
893.
Boys ML Bian F Kramer JB Chio CL Ren XD Chen H Barrett SD Sexton KE Iula DM Filzen GF Nguyen MN Angell P Downs VL Wang Z Raheja N Ellsworth EL Fakhoury S Bratton LD Keller PR Gowan R Drummond EM Maiti SN Hena MA Lu L McConnell P Knafels JD Thanabal V Sun F Alessi D McCarthy A Zhang E Finzel BC Patel S Ciotti SM Eisma R Payne NA Gilbertsen RB Kostlan CR Pocalyko DJ Lala DS 《Bioorganic & medicinal chemistry letters》2012,22(10):3392-3397
A series of 2-(1H-pyrazol-1-yl)pyridines are described as inhibitors of ALK5 (TGFβ receptor I kinase). Modeling compounds in the ALK5 kinase domain enabled some optimization of potency via substitutions on the pyrazole core. One of these compounds PF-03671148 gave a dose dependent reduction in TGFβ induced fibrotic gene expression in human fibroblasts. A similar reduction in fibrotic gene expression was observed when PF-03671148 was applied topically in a rat wound repair model. Thus these compounds have potential utility for the prevention of dermal scarring. 相似文献
894.
Zhi D Zhang S Qureshi F Zhao Y Cui S Wang B Chen H Wang Y Zhao D 《Bioorganic & medicinal chemistry letters》2012,22(11):3837-3841
We have introduced a convenient synthesis method for carbamate-linked cationic lipids. Two cationic lipids N-[1-(2,3-didodecylcarbamoyloxy)propyl]-N,N,N-trimethylammonium iodide (DDCTMA) and N-[1-(2,3-didodecyl carbamoyloxy)propyl]-N-ethyl-N,N-dimethylammonium iodide (DDCEDMA), with identical length of hydrocarbon chains, alternative quaternary ammonium heads, carbamate linkages between hydrocarbon chains and quaternary ammonium heads, were synthesized for liposome-mediated gene delivery. Liposomes composed of DDCEDMA and DOPE in 1:1 ratio exhibited a lower zeta potential as compared to those made of pure DDCEDMA alone, which influences their DNA-binding ability. pGFP-N2 plasmid was transferred by cationic liposomes formed from the above cationic lipids into Hela and Hep-2 cells, and the transfection efficiency of some of cationic liposomes was superior or parallel to that of two commercial transfection agents, Lipofectamine2000 and DOTAP. Combined with the results of the agarose gel electrophoresis and transfection experiment, the DNA-binding ability of cationic lipids was too strong to release DNA from complex in the transfection, which could lead to relative low transfection efficiency and high cytotoxicity. 相似文献
895.
X Chai Z Guan S Yu Q Zhao H Hu Y Zou X Tao Q Wu 《Bioorganic & medicinal chemistry letters》2012,22(18):5849-5852
In order to search for drugs with excellent anti-inflammatory activities, a series of novel sinomenine derivatives were designed, synthesized, and evaluated for their inhibition activities against NF-κB activation induced by lipopolysaccharide (LPS). Compared with the natural parent sinomenine, compounds 2a-w showed higher activity, while compounds 1a-o showed similar activity against NF-κB. Moreover, a molecular model for the binding between compound 2v and the active site of p50 was provided on the basis of the computational docking results. 相似文献
896.
Li J Hua HM Tang YB Zhang S Ohkoshi E Lee KH Xiao Zy 《Bioorganic & medicinal chemistry letters》2012,22(13):4293-4295
Because prior studies have shown inconsistency between structure-activity relationships for podophyllotoxin derivatives as topoisomerase II inhibitors and cytotoxic agents, eight novel podophyllotoxin analogs were synthesized to further explore the effects of structural variations on both A and D rings on activity. The new compounds contain a 4,5-dimethoxy substituted A ring and opened D-ring variants and were prepared by appropriate functional and stereochemical operations at the methylenedioxy group, C7, C8, and C8'. Four compounds (15, 18, 21 and 22) demonstrated noticeable inhibitory activity against A549, DU145, KB and KBvin tumor cells, and the most active compound 18 showed IC(50) values less than 10 μg/mL. 相似文献
897.
Tang J Dai Y Zhang H Culleton RL Liu Y Zhao S Wang X Guan X Kaneko O Zhu Y 《Parasitology》2012,139(6):709-715
Plasmodium rhoptry neck protein 2 (RON2), which is released from the neck portion of the merozoite rhoptries and interacts with the microneme protein Apical Membrane Antigen 1 (AMA1), plays a crucial role in erythrocyte invasion. In this study, we sequenced the Plasmodium vivax RON2 gene from 19 P. vivax isolates collected in central China in order to establish whether this protein is under positive diversifying selection, which may occur as a result of protective host immune pressure?. In comparison with the P. vivax Sal-1 reference line, we found 10 amino acid substitutions dispersed throughout the open reading frame as well as indels caused by polymorphism in a repeat unit (21-23 repeats of (Q/E/K/N/H)(G/D)G(H/L/Y/P)G) in the second tandem repeat region located at amino acid positions 541-650. A McDonald-Kreitman test with RON2 sequences from the primate malaria parasite Plasmodium knowlesi, detected significant departure from neutrality in the PvRON2 3' region (nucleotide positions 2668-6609). These results suggest that the PvRON2 gene has evolved under positive diversifying selection. 相似文献
898.
The determination of final organ size is a highly coordinated and complex process that relies on the precise regulation of cell number and/or cell size. Perturbation of organ size control contributes to many human diseases, including hypertrophy, degenerative diseases, and cancer. Hippo and TOR are among the key signaling pathways involved in the regulation of organ size through their respective functions in the regulation of cell number and cell size. Here, we review the general mechanisms that regulate organ growth, describe how Hippo and TOR control key aspects of growth, and discuss recent findings that highlight a possible coordination between Hippo and TOR in organ size regulation. 相似文献
899.
Background
All honey bee species (Apis spp) share the same sex determination mechanism using the complementary sex determination (csd) gene. Only individuals heterogeneous at the csd allele develop into females, and the homozygous develop into diploid males, which do not survive. The honeybees are therefore under selection pressure to generate new csd alleles. Previous studies have shown that the csd gene is under balancing selection. We hypothesize that due to the long separation from the mainland of Hainan Island, China, that the giant honey bees (Apis dorsata) should show a founder effect for the csd gene, with many different alleles clustered together, and these would be absent on the mainland.Methodology/Principal Findings
We sampled A. dorsata workers from both Hainan and Guangxi Provinces and then cloned and sequenced region 3 of the csd gene and constructed phylogenetic trees. We failed to find any clustering of the csd alleles according to their geographical origin, i.e. the Hainan and Guangxi samples did not form separate clades. Further analysis by including previously published csd sequences also failed to show any clade-forming in both the Philippines and Malaysia.Conclusions/Significance
Results from this study and those from previous studies did not support the expectations of a founder effect. We conclude that because of the extremely high mating frequency of A. dorsata queens, a founder effect does not apply in this species. 相似文献900.