Swellmeen, Lubna published the artcileStructure based drug design of Pim-1 kinase followed by pharmacophore guided synthesis of quinolone-based inhibitors, Name: Ethyl 3-(dimethylamino)acrylate, the publication is Bioorganic & Medicinal Chemistry (2017), 25(17), 4855-4875, database is CAplus and MEDLINE.
Over expression of Human phosphatidylinositol mannoside kinases isoform 1 (Pim-1 kinase) has been reported in several leukemia and solid tumors. The authors’ continuous interest to reveal the secrecies of the mysterious Pim-1 kinase binding pocket has led the authors to employ a structure based drug design procedure based on receptor-ligand pharmacophore generation protocol implemented in Discovery Studio 4.5 (DS 4.5). Subsequently, the authors collected 104 crystal structures of Pim-1 kinase from the Protein Data Bank (PDB) and used them to generate pharmacophores based on the anticipated co-crystallized ligand-Pim 1 kinase receptor interactions. All selected pharmacophoric features were enumerated and only those that had corresponding valuable receptor-ligand interactions were retained. This was followed by modeling all pharmacophore combinations and scoring them according to their Receiver Operating Characteristic (ROC) curve anal. parameters as well as a DS.4.5 built-in Genetic Function Algorithm (GFA) validating model. Accordingly, 111 pharmacophores resulted with acceptable ROC performances; 1XWS_2_04, 2BIK_2_06, and 1XWS_2_06 (ROC AUC value of: 0.770, 0.743 and 0.741 resp.) were the best pharmacophores. These pharmacophores were employed to guide the synthesis of new series of 7-[(2-Carboxyethyl)amino]-1-substituted-6-fluoro-8-nitro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid and their reduced 8-amino derivatives The synthesized compounds were later evaluated for their Pim-1 kinase inhibitory potencies. Of which the most potent illustrated an IC50 value of 0.29 μM against Pim-1 kinase.
Bioorganic & Medicinal Chemistry published new progress about 924-99-2. 924-99-2 belongs to esters-buliding-blocks, auxiliary class Alkenyl,Amine,Aliphatic hydrocarbon chain,Ester, name is Ethyl 3-(dimethylamino)acrylate, and the molecular formula is C12H6NNaO4, Name: Ethyl 3-(dimethylamino)acrylate.
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