During the last 15 years, structures for half from the identified target kinases were deposited in PDB, in order that generally there is enough data for structure-based medication repositioning on the market. individual P-values for every compound-targets prediction.(XLSX) pone.0233089.s002.xlsx (151K) GUID:?AC3F92A2-AF78-4368-820F-E4C427E90873 S3 Document: Protein-drug predictions. Set of 1828 predictions between your 157 compounds as well as the 22 goals. It includes the substance id (CID), the proteins target, the complicated id (pdbid:hetid:string:placement) from the template, the complicated id from the hit, the technique producing the prediction as well as the p-value from the prediction.(XLSX) pone.0233089.s003.xlsx (68K) GUID:?7A5FBB86-832E-400B-8552-BBCAA2380724 S4 Document: Activity assay. Results of the kinase activity assay performed for the 111 purchased compounds. It contains the compound name, the target name and the enzyme activity value of 2 data points at 1 and 10 M.(XLSX) Lannaconitine pone.0233089.s004.xlsx (27K) GUID:?942E4A8E-05A9-452D-A894-477EFDE3E977 S5 File: Bcell assay. Results of the efficacy and cytotoxicity tests of 16 of our kinase inhibitors (Compound column) on B-cell and T-cell lines. The four type of assays are reported: B-cell efficacy, T-cell efficacy, Cytotoxicity/ WST1 RPMI 1788 and Cytotoxicity/ WST-1 Jurkat. For each assay the mean of 4 different independent measures and the standard deviation (SD) are reported. Three different indexes have been calculated: Therapeutic Index (TI)/ WST1 RPMI 1788/B-cell (B-cell/B-cell), Therapeutic Index (TI)/ WST1 Jurkat/B-cell (T-cell/B-cell), and Selectivity Index (SI)/ MLR/B-cell (T-cell/B-cell). Mycophenolate Mofetyl and Lannaconitine Cyclosporine A have been used as positive controls.(XLSX) pone.0233089.s005.xlsx (8.2K) GUID:?0567A0FF-5220-433D-AD14-82E4FCE1971A S1 Fig: RNAi screening for target identification. The level of inhibition of upregulation (y), of CD70 (dark blue Lannaconitine dots) and CD80 (light blue dots) for each clone of the selected genes (x axe) have been plotted plotted. The clones laying in the bottom part of the graph with y 0 (red part), showed an expression of the surface receptor (Ssample or Ss on the side bar) higher than the stimulated control cells (Sctrl or Sc); the clones (Ss) with 0 y 1 (yellow part) had a level of CD70/CD80 expression lower than the stimulated controls (Sc) but higher than the non-stimulated control cells (NSctrl) or NSc); the clones (Ss) placed in the area with y 1 (green part) showed an exprssion of the activation markers lower also than the non-stimulated controls NSc. Those genes have been selected for showing the y of at least one clone above both the threshold of 0.8 for CD70 (dark blue dotted line) and 0.5 for CD80 (light blue dotted line).(EPS) pone.0233089.s006.eps (1.0M) GUID:?37CC7AC6-31DF-4172-98FE-F6E839D01F41 S2 Fig: Available structures for 22 targets over time. Over the last 15 years, structures for half of the identified target kinases were deposited in PDB, so that today there is sufficient data for structure-based drug repositioning available. Before the year 2002, this type of screening would not have been possible. In the Lannaconitine future, it will further improve.(EPS) pone.0233089.s007.eps (36K) GUID:?3FF7E31B-52B0-4CCA-9D0B-29E4A6BF3E9B S1 Table: Literature evidence for a targets association to disease. Links in litterature between each gene target (Target column) and some pathological conditions (Disease column) such as Cancer, Tumors of Immune System (Lymphoma, Leukemia and Multiple Myeloma), and Autoimmune Diseases (Inflammatory Bowel Disease, Psoriasis, Lupus Erythematosus, Graves Disease and Rheumatoid Arthritis) are reported (PMID column).(XLSX) pone.0233089.s008.xlsx (5.9K) GUID:?EC55010F-CBA2-4DB5-8794-D6D214B2E1E4 Data Availability StatementAll relevant data are within the paper and its Supporting Information files. Abstract Many drugs are promiscuous and bind to multiple targets. On the one hand, these targets may be linked to unwanted side effects, but on the other, they may achieve a combined desired effect (polypharmacology) or represent multiple diseases (drug repositioning). With the growth of 3D structures of drug-target complexes, it is today possible to study drug promiscuity at the structural level and to screen vast amounts of drug-target interactions to predict side effects, polypharmacological potential, and repositioning opportunities. MECOM Here, we pursue such an approach to Lannaconitine identify drugs inactivating B-cells, whose dysregulation can.
During the last 15 years, structures for half from the identified target kinases were deposited in PDB, in order that generally there is enough data for structure-based medication repositioning on the market
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