References (3)

Title : Discovery and synthesis of tetrahydropyrimidinedione-4-carboxamides as endothelial lipase inhibitors - Hu_2018_Bioorg.Med.Chem.Lett_28_3721
Author(s) : Hu CH , Wang TC , Qiao JX , Haque L , Chen AYA , Taylor DS , Ying X , Onorato JM , Galella M , Shen H , Huang CS , Toussaint N , Li YX , Abell L , Adam LP , Gordon D , Wexler RR , Finlay HJ
Ref : Bioorganic & Medicinal Chemistry Lett , 28 :3721 , 2018
Abstract : Endothelial lipase (EL) inhibitors have been shown to elevate HDL-C levels in pre-clinical murine models and have potential benefit in prevention and treatment of cardiovascular diseases. Modification of the 1-ethyl-3-hydroxy-1,5-dihydro-2H-pyrrol-2-one (DHP) lead, 1, led to the discovery of a series of potent tetrahydropyrimidinedione (THP) EL inhibitors. Synthesis and SAR studies including modification of the amide group, together with changes on the pyrimidinone core led to a series of arylcycloalkyl, indanyl, and tetralinyl substituted 5-amino or 5-hydroxypyrimidinedione-4-carboxamides. Several compounds were advanced to PK evaluation. Among them, compound 4a was one of the most potent with measurable EL(HDL) hSerum potency and compound 3g demonstrated the best overall pharmacokinetic parameters.
ESTHER : Hu_2018_Bioorg.Med.Chem.Lett_28_3721
PubMedSearch : Hu_2018_Bioorg.Med.Chem.Lett_28_3721
PubMedID: 30348490

Title : Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans - Haas_2009_Nature_461_393
Author(s) : Haas BJ , Kamoun S , Zody MC , Jiang RH , Handsaker RE , Cano LM , Grabherr M , Kodira CD , Raffaele S , Torto-Alalibo T , Bozkurt TO , Ah-Fong AM , Alvarado L , Anderson VL , Armstrong MR , Avrova A , Baxter L , Beynon J , Boevink PC , Bollmann SR , Bos JI , Bulone V , Cai G , Cakir C , Carrington JC , Chawner M , Conti L , Costanzo S , Ewan R , Fahlgren N , Fischbach MA , Fugelstad J , Gilroy EM , Gnerre S , Green PJ , Grenville-Briggs LJ , Griffith J , Grunwald NJ , Horn K , Horner NR , Hu CH , Huitema E , Jeong DH , Jones AM , Jones JD , Jones RW , Karlsson EK , Kunjeti SG , Lamour K , Liu Z , Ma L , Maclean D , Chibucos MC , McDonald H , McWalters J , Meijer HJ , Morgan W , Morris PF , Munro CA , O'Neill K , Ospina-Giraldo M , Pinzon A , Pritchard L , Ramsahoye B , Ren Q , Restrepo S , Roy S , Sadanandom A , Savidor A , Schornack S , Schwartz DC , Schumann UD , Schwessinger B , Seyer L , Sharpe T , Silvar C , Song J , Studholme DJ , Sykes S , Thines M , van de Vondervoort PJ , Phuntumart V , Wawra S , Weide R , Win J , Young C , Zhou S , Fry W , Meyers BC , van West P , Ristaino J , Govers F , Birch PR , Whisson SC , Judelson HS , Nusbaum C
Ref : Nature , 461 :393 , 2009
Abstract : Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement. To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population. Current annual worldwide potato crop losses due to late blight are conservatively estimated at $$6.7 billion. Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars. Here we report the sequence of the P. infestans genome, which at approximately 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for approximately 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.
ESTHER : Haas_2009_Nature_461_393
PubMedSearch : Haas_2009_Nature_461_393
PubMedID: 19741609
Gene_locus related to this paper: phyin-ENDO2 , phyin-q2m440 , phyin-q58g92 , phyit-d0mqp1 , phyit-d0mqp2 , phyit-d0mt75 , phyit-d0muv1 , phyit-d0mv34 , phyit-d0mv35 , phyit-d0mwf9 , phyit-d0mxu5 , phyit-d0n935 , phyit-d0nax9 , phyit-d0nfs3 , phyit-d0nhj2 , phyit-d0nhj4 , phyit-d0nhj8 , phyit-d0ni28 , phyit-d0nj14 , phyit-d0nj53 , phyit-d0nj54 , phyit-d0njf2 , phyit-d0nkm4 , phyit-d0nr53 , phyit-d0nrb1 , phyit-d0nrk9 , phyit-d0nrl4 , phyit-d0ns26 , phyit-d0ns42 , phyit-d0ns43 , phyit-d0nsr8 , phyit-d0nu41 , phyit-d0nvt3 , phyit-d0nwb6 , phyit-d0nwm8 , phyit-d0nzc0 , phyit-d0nzc1 , phyit-d0p0z1 , phyit-d0p3z2 , phyit-kex1 , phyit-d0n6q6 , phyit-d0n4i8 , phyit-d0mqf7 , phyit-d0n5g6

Title : Expression pattern of the single-minded gene in zebrafish embryos - Wen_2002_Mech.Dev_110_231
Author(s) : Wen HJ , Wang Y , Chen SH , Hu CH
Ref : Mech Dev , 110 :231 , 2002
Abstract : Recently we isolated a homolog of the Drosophila single-minded (sim) gene from a zebrafish cDNA library. The 4380-bp of zebrafish sim cDNA encodes a polypeptide of 585 amino acids with strikingly conserved bHLH and PAS A/B domains in the amino-terminal region. During embryogenesis, sim mRNA appears in the animal hemisphere as early as 3 h post-fertilization and is expressed in a widespread pattern throughout the epiblast at the 75% epiboly stage. During the segmentation stage, sim mRNA is prominently expressed in the primordium of the hindbrain and appears as a transverse stripe in the epithelial layers of the mid-diencephalic boundary (MDB). During the pharyngula stage, sim is no longer expressed in the hindbrain, but continues to be expressed in the MDB and extends to the caudal diencephalon along the ventral midline. In addition, sim mRNA is prominent in the two pharyngeal arches. During the larval stage, sim mRNA is transcribed in the esophagus, liver, pancreas, and intestine. In contrast, sim mRNA is no longer detectable in the forebrain after hatching. In adult fish, sim is widely expressed in brain, eyes, gill, heart, liver, and intestine.
ESTHER : Wen_2002_Mech.Dev_110_231
PubMedSearch : Wen_2002_Mech.Dev_110_231
PubMedID: 11744389