SEARCH OF NEW STRUCTURAL SCAFFOLDS FOR SPHINGOSINE KINASE 1 INHIBITORS

MARCELA VETTORAZZI; ROJAS, SEBASTIÁN; LUCAS J GUTIERREZ; ALVAREZ, SERGIO; ENRIZ R D

San Miguel de Tucuman

Congreso; Congreso de SAB; 2016

Soc Argentina de BIOFISICA

Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid Sphingosine kinase 1 (SphK1), the enzyme that produces bioactive sphingolipid metabolite, sphingosinemetabolite, sphingosinemetabolite, sphingosinemetabolite, sphingosinemetabolite, sphingosinemetabolite, sphingosinemetabolite, sphingosinemetabolite, sphingosinemetabolite, sphingosinemetabolite, sphingosinemetabolite, sphingosinemetabolite, sphingosinemetabolite, sphingosinemetabolite, sphingosinemetabolite, sphingosinemetabolite, sphingosinemetabolite, sphingosinemetabolite, sphingosine-1-phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic phosphate, is a promising new molecular target for therapeutic intervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseasesintervention in cancer and inflammatory diseases1,21,21,2. In view of it. In view of it. In view of it. In view of it. In view of it. In view of it. In view of it. In view of it. In view of it. In view of it. In view of its importance, the main s importance, the main s importance, the main s importance, the main s importance, the main s importance, the main s importance, the main s importance, the main s importance, the main s importance, the main s importance, the main s importance, the main s importance, the main s importance, the main s importance, the main s importance, the main objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing objective of this work was to find new and more potent inhibitors for enzyme possessing different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and different structural scaffolds than those of the known inhibitors. Our theoretical and experimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new strexperimental study has allowed us to find two new structural scaffolds (three new uctural scaffolds (three new uctural scaffolds (three new uctural scaffolds (three new uctural scaffolds (three new uctural scaffolds (three new uctural scaffolds (three new uctural scaffolds (three new uctural scaffolds (three new uctural scaffolds (three new uctural scaffolds (three new uctural scaffolds (three new uctural scaffolds (three new uctural scaffolds (three new uctural scaffolds (three new uctural scaffolds (three new compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then compounds), which could be used as starting structures for the design and then development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual development of new inhibitors SphK1. Our study was carried out in different steps: virtual screening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modescreening, synthesis, bioassays and molecular modeling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new ling. From our results, we propose new dihydrobenzo[b]pyrimido[5,4dihydrobenzo[b]pyrimido[5,4dihydrobenzo[b]pyrimido[5,4dihydrobenzo[b]pyrimido[5,4dihydrobenzo[b]pyrimido[5,4dihydrobenzo[b]pyrimido[5,4dihydrobenzo[b]pyrimido[5,4dihydrobenzo[b]pyrimido[5,4dihydrobenzo[b]pyrimido[5,4dihydrobenzo[b]pyrimido[5,4dihydrobenzo[b]pyrimido[5,4dihydrobenzo[b]pyrimido[5,4dihydrobenzo[b]pyrimido[5,4dihydrobenzo[b]pyrimido[5,4dihydrobenzo[b]pyrimido[5,4dihydrobenzo[b]pyrimido[5,4dihydrobenzo[b]pyrimido[5,4-f]azepinesf]azepinesf]azepinesf]azepinesf]azepinesf]azepinesf]azepinesf]azepines, , and and and and two two two pyridinylpyridinylpyridinylpyridinylpyridinyl-piperazinylpiperazinylpiperazinylpiperazinylpiperazinylpiperazinyl-ethylethylethyl-phenylphenylphenylphenylphenylphenyl-O-alkylalkylalkylalkyl-carbamatecarbamatecarbamatecarbamatecarbamatecarbamate derivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the developmentderivatives as initial structures for the development of new inhibitors for SphK1. In of new inhibitors for SphK1. In of new inhibitors for SphK1. In of new inhibitors for SphK1. In of new inhibitors for SphK1. In of new inhibitors for SphK1. In of new inhibitors for SphK1. In of new inhibitors for SphK1. In of new inhibitors for SphK1. In of new inhibitors for SphK1. In of new inhibitors for SphK1. In of new inhibitors for SphK1. In of new inhibitors for SphK1. In of new inhibitors for SphK1. In of new inhibitors for SphK1. In of new inhibitors for SphK1. In of new inhibitors for SphK1. In of new inhibitors for SphK1. In of new inhibitors for SphK1. In of new inhibitors for SphK1. In addition, our molecular modeladdition, our molecular modeladdition, our molecular modeladdition, our molecular modeladdition, our molecular modeladdition, our molecular modeladdition, our molecular modeladdition, our molecular modeladdition, our molecular modeladdition, our molecular modeladdition, our molecular modeladdition, our molecular modeladdition, our molecular modeladdition, our molecular modeladdition, our molecular modeladdition, our molecular modeladdition, our molecular modeladdition, our molecular modeladdition, our molecular modeladdition, our molecular modeladdition, our molecular modeladdition, our molecular modeling study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in ing study using QTAIM calculations, allowed us to describe in detail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Liganddetail the molecular interactions that stabilize different Ligand-Receptor complexes. Such Receptor complexes. Such Receptor complexes. Such Receptor complexes. Such Receptor complexes. Such Receptor complexes. Such Receptor complexes. Such Receptor complexes. Such Receptor complexes. Such Receptor complexes. Such Receptor complexes. Such Receptor complexes. Such Receptor complexes. Such Receptor complexes. Such Receptor complexes. Such Receptor complexes. Such Receptor complexes. Such analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to analyses indicate that the cationic head of different compounds must be refined in order to