Kevin R. Lynch

Foster, D. J., Dunnavant, K., Shrader, C. W., LoPresti, M., Seay, S., Kharel, Y., . . . Santos, W. L. (2024). Discovery of Potent, Orally Bioavailable Sphingosine-1-Phosphate Transporter (Spns2) Inhibitors. JOURNAL OF MEDICINAL CHEMISTRY. doi:10.1021/acs.jmedchem.4c00879

Kharel, Y., Huang, T., Dunnavant, K., Foster, D., Souza, G., Nimchuk, K. E., . . . Lynch, K. R. (2024). Assessing Spns2-dependent S1P Transport as a Prospective Therapeutic Target.. bioRxiv. doi:10.1101/2024.03.26.586765

Busey, G. W., Manjegowda, M. C., Huang, T., Iobst, W. H., Naphade, S. S., Kennedy, J. A., . . . Desai, B. N. (2023). Analogs of FTY720 inhibit TRPM7 but not S1PRs and exert multimodal anti-inflammatory effects. JOURNAL OF GENERAL PHYSIOLOGY, 156(1). doi:10.1085/jgp.202313419

Kharel, Y., Huang, T., Santos, W. L., & Lynch, K. R. (2023). Assay of Sphingosine 1-phosphate Transporter Spinster Homolog 2 (Spns2) Inhibitors. SLAS DISCOVERY, 28(6), 284-287. doi:10.1016/j.slasd.2023.07.001

Burgio, A. L., Shrader, C. W., Kharel, Y., Huang, T., Salamoun, J. M., Lynch, K. R., & Santos, W. L. (2023). 2-Aminobenzoxazole Derivatives as Potent Inhibitors of the Sphingosine-1-Phosphate Transporter Spinster Homolog 2 (Spns2). JOURNAL OF MEDICINAL CHEMISTRY, 66(8), 5873-5891. doi:10.1021/acs.jmedchem.3c00149

Tanaka, S., Zheng, S., Kharel, Y., Fritzemeier, R. G., Huang, T., Foster, D., . . . Okusa, M. D. (2022). Sphingosine 1-phosphate signaling in perivascular cells enhances inflammation and fibrosis in the kidney. SCIENCE TRANSLATIONAL MEDICINE, 14(658). doi:10.1126/scitranslmed.abj2681

Pashikanti, S., Foster, D. J., Kharel, Y., Brown, A. M., Bevan, D. R., Lynch, K. R., & Santos, W. L. (2022). Sphingosine Kinase 2 Inhibitors: Rigid Aliphatic Tail Derivatives Deliver Potent and Selective Analogues. ACS BIO & MED CHEM AU, 2(5), 469-489. doi:10.1021/acsbiomedchemau.2c00017

Oyewole, O. O., Dunnavant, K., Bhattarai, S., Kharel, Y., Lynch, K. R., Santos, W. L., & Reid, S. P. (2022). A Novel Sphingosine Kinase Inhibitor Suppresses Chikungunya Virus Infection. VIRUSES-BASEL, 14(6). doi:10.3390/v14061123

Fritzemeier, R., Foster, D., Peralta, A., Payette, M., Kharel, Y., Huang, T., . . . Santos, W. L. (2022). Discovery of In Vivo Active Sphingosine-1-phosphate Transporter (Spns2) Inhibitors. JOURNAL OF MEDICINAL CHEMISTRY, 65(11), 7656-7681. doi:10.1021/acs.jmedchem.1c02171

Congdon, M., Fritzemeier, R. G., Kharel, Y., Brown, A. M., Serbulea, V., Bevan, D. R., . . . Santos, W. L. (2021). Probing the substitution pattern of indole-based scaffold reveals potent and selective sphingosine kinase 2 inhibitors. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 212. doi:10.1016/j.ejmech.2020.113121

Li, H., Sibley, C. D., Kharel, Y., Huang, T., Brown, A. M., Wonilowicz, L. G., . . . Santos, W. L. (2021). Lipophilic tail modifications of 2-(hydroxymethyl)pyrrolidine scaffold reveal dual sphingosine kinase 1 and 2 inhibitors. BIOORGANIC & MEDICINAL CHEMISTRY, 30. doi:10.1016/j.bmc.2020.115941

Kharel, Y., Huang, T., Salamon, A., Harris, T. E., Santos, W. L., & Lynch, K. R. (2020). Mechanism of sphingosine 1-phosphate clearance from blood. BIOCHEMICAL JOURNAL, 477(5), 925-935. doi:10.1042/BCJ20190730

Sibley, C. D., Morris, E. A., Kharel, Y., Brown, A. M., Huang, T., Bevan, D. R., . . . Santos, W. L. (2020). Discovery of a Small Side Cavity in Sphingosine Kinase 2 that Enhances Inhibitor Potency and Selectivity. JOURNAL OF MEDICINAL CHEMISTRY, 63(3), 1178-1198. doi:10.1021/acs.jmedchem.9b01508

Adamiak, M., Chelvarajan, L., Lynch, K. R., Santos, W. L., Abdel-Latif, A., & Ratajczak, M. Z. (2018). Correction: Mobilization studies in mice deficient in sphingosine kinase 2 support a crucial role of the plasma level of sphingosine-1-phosphate in the egress of hematopoietic stem progenitor cells.. Oncotarget, 9(75), 34189. doi:10.18632/oncotarget.26195

Mehaffey, J. H., Charles, E. J., Narahari, A. K., Schubert, S., Laubach, V. E., Teman, N. R., . . . Sharma, A. K. (2018). Increasing circulating sphingosine-1-phosphate attenuates lung injury during ex vivo lung perfusion. JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, 156(2), 910-917. doi:10.1016/j.jtcvs.2018.02.090

Cao, R., Li, J., Kharel, Y., Zhang, C., Morris, E., Santos, W. L., . . . Hu, S. (2018). Photoacoustic microscopy reveals the hemodynamic basis of sphingosine 1-phosphate-induced neuroprotection against ischemic stroke. THERANOSTICS, 8(22), 6111-6120. doi:10.7150/thno.29435

Kharel, Y., Agah, S., Huang, T., Mendelson, A. J., Eletu, O. T., Barkey-Bircannl, P., . . . Lynch, K. R. (2018). Saccharomyces cerevisiae as a platform for assessing sphingolipid lipid kinase inhibitors. PLOS ONE, 13(4). doi:10.1371/journal.pone.0192179

Adamiak, M., Chelvarajan, L., Lynch, K. R., Santos, W. L., Abdel-Latif, A., & Ratajczak, M. Z. (2017). Mobilization studies in mice deficient in sphingosine kinase 2 support a crucial role of the plasma level of sphingosine-1-phosphate in the egress of hematopoietic stem progenitor cells.. Oncotarget, 8(39), 65588-65600. doi:10.18632/oncotarget.19514

Adamiak, M., Chelvarajan, L., Lynch, K. R., Santos, W. L., Abdel-Latif, A., & Ratajczak, M. Z. (2017). Mobilization studies in mice deficient in sphingosine kinase 2 support a crucial role of the plasma level of sphingosine-1-phosphate in the egress of hematopoietic stem progenitor cells. ONCOTARGET, 8(39), 65588-65600. doi:10.18632/oncotarget.19514

Childress, E. S., Kharel, Y., Brown, A. M., Bevan, D. R., Lynch, K. R., & Santos, W. L. (2017). Transforming Sphingosine Kinase 1 Inhibitors into Dual and Sphingosine Kinase 2 Selective Inhibitors: Design, Synthesis, and in Vivo Activity. JOURNAL OF MEDICINAL CHEMISTRY, 60(9), 3933-3957. doi:10.1021/acs.jmedchem.7b00233

Bajwa, A., Huang, L., Kurmaeva, E., Ye, H., Dondeti, K. R., Chroscicki, P., . . . Okusa, M. D. (2017). Sphingosine Kinase 2 Deficiency Attenuates Kidney Fibrosis via IFN-γ. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 28(4), 1145-1161. doi:10.1681/ASN.2016030306

Lynch, K. R., Thorpe, S. B., & Santos, W. L. (2016). Sphingosine kinase inhibitors: a review of patent literature (2006-2015). EXPERT OPINION ON THERAPEUTIC PATENTS, 26(12), 1409-1416. doi:10.1080/13543776.2016.1226282

Perry, H. M., Huang, L., Ye, H., Liu, C., Sung, S. -S. J., Lynch, K. R., . . . Okusa, M. D. (2016). Endothelial Sphingosine 1-Phosphate Receptor-1 Mediates Protection and Recovery from Acute Kidney Injury. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 27(11), 3383-3393. doi:10.1681/ASN.2015080922

Houck, J. D., Dawson, T. K., Kennedy, A. J., Kharel, Y., Naimon, N. D., Field, S. D., . . . Macdonald, T. L. (2016). Structural Requirements and Docking Analysis of Amidine-Based Sphingosine Kinase 1 Inhibitors Containing Oxadiazoles. ACS MEDICINAL CHEMISTRY LETTERS, 7(5), 487-492. doi:10.1021/acsmedchemlett.6b00002

Congdon, M. D., Kharel, Y., Brown, A. M., Lewis, S. N., Bevan, D. R., Lynch, K. R., & Santos, W. L. (2016). Structure-Activity Relationship Studies and Molecular Modeling of Naphthalene-Based Sphingosine Kinase 2 Inhibitors. ACS MEDICINAL CHEMISTRY LETTERS, 7(3), 229-234. doi:10.1021/acsmedchemlett.5b00304

Kharel, Y., Morris, E. A., Congdon, M. D., Thorpe, S. B., Tomsig, J. L., Santos, W. L., & Lynch, K. R. (2015). Sphingosine Kinase 2 Inhibition and Blood Sphingosine 1-Phosphate Levels. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 355(1), 23-31. doi:10.1124/jpet.115.225862

Stone, M. L., Sharma, A. K., Zhao, Y., Charles, E. J., Huerter, M. E., Johnston, W. F., . . . Laubach, V. E. (2015). Sphingosine-1-phosphate receptor 1 agonism attenuates lung ischemia-reperfusion injury. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 308(12), L1245-L1252. doi:10.1152/ajplung.00302.2014

Congdon, M. D., Childress, E. S., Patwardhan, N. N., Gumkowski, J., Morris, E. A., Kharel, Y., . . . Santos, W. L. (2015). Structure-activity relationship studies of the lipophilic tail region of sphingosine kinase 2 inhibitors. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 25(21), 4956-4960. doi:10.1016/j.bmcl.2015.03.041

Patwardhan, N. N., Morris, E. A., Kharel, Y., Raje, M. R., Gao, M., Tomsig, J. L., . . . Santos, W. L. (2015). Structure-Activity Relationship Studies and in Vivo Activity of Guanidine-Based Sphingosine Kinase Inhibitors: Discovery of SphK1-and SphK2-Selective Inhibitors. JOURNAL OF MEDICINAL CHEMISTRY, 58(4), 1879-1899. doi:10.1021/jm501760d

Santos, W. L., & Lynch, K. R. (2015). Drugging Sphingosine Kinases. ACS CHEMICAL BIOLOGY, 10(1), 225-233. doi:10.1021/cb5008426

Bajwa, A., Rosin, D. L., Chroscicki, P., Lee, S., Dondeti, K., Ye, H., . . . Okusa, M. D. (2015). Sphingosine 1-Phosphate Receptor-1 Enhances Mitochondrial Function and Reduces Cisplatin-Induced Tubule Injury. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 26(4), 908-925. doi:10.1681/ASN.2013121351

Ogle, M. E., Sefcik, L. S., Awojoodu, A. O., Chiappa, N. F., Lynch, K., Peirce-Cottler, S., & Botchwey, E. A. (2014). Engineering in vivo gradients of sphingosine-1-phosphate receptor ligands for localized microvascular remodeling and inflammatory cell positioning. ACTA BIOMATERIALIA, 10(11), 4704-4714. doi:10.1016/j.actbio.2014.08.007

Kharel, Y., Raje, M., Gao, M., Gellett, A. M., Tomsig, J. L., Lynch, K. R., & Santos, W. L. (2012). Sphingosine kinase type 2 inhibition elevates circulating sphingosine 1-phosphate. BIOCHEMICAL JOURNAL, 447, 149-157. doi:10.1042/BJ20120609

Bajwa, A., Huang, L., Ye, H., Dondeti, K., Song, S., Rosin, D. L., . . . Okusa, M. D. (2012). Dendritic Cell Sphingosine 1-Phosphate Receptor-3 Regulates Th1-Th2 Polarity in Kidney Ischemia-Reperfusion Injury. JOURNAL OF IMMUNOLOGY, 189(5), 2584-2596. doi:10.4049/jimmunol.1200999

Gellett, A. M., Kharel, Y., Sunkara, M., Morris, A. J., & Lynch, K. R. (2012). Biosynthesis of alkyl lysophosphatidic acid by diacylglycerol kinases. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 422(4), 758-763. doi:10.1016/j.bbrc.2012.05.077

Lynch, K. R. (2012). Building a better sphingosine kinase-1 inhibitor.. The Biochemical journal, 444(1), e1-e2. doi:10.1042/bj20120567

Knott, K., Kharel, Y., Raje, M. R., Lynch, K. R., & Santos, W. L. (2012). Effect of alkyl chain length on sphingosine kinase 2 selectivity. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 22(22), 6817-6820. doi:10.1016/j.bmcl.2012.01.050

Kharel, Y., Mathews, T. P., Gellett, A. M., Tomsig, J. L., Kennedy, P. C., Moyer, M. L., . . . Lynch, K. R. (2011). Sphingosine kinase type 1 inhibition reveals rapid turnover of circulating sphingosine 1-phosphate. BIOCHEMICAL JOURNAL, 440, 345-353. doi:10.1042/BJ20110817

Raje, M. R., Knott, K., Kharel, Y., Bissel, P., Lynch, K. R., & Santos, W. L. (2012). Design, synthesis and biological activity of sphingosine kinase 2 selective inhibitors. BIOORGANIC & MEDICINAL CHEMISTRY, 20(1), 183-194. doi:10.1016/j.bmc.2011.11.011

Callihan, P., Zitomer, N. C., Stoeling, M. V., Kennedy, P. C., Lynch, K. R., Riley, R. T., & Hooks, S. B. (2012). Distinct generation, pharmacology, and distribution of sphingosine 1-phosphate and dihydro-sphingosine 1-phosphate in human neural progenitor cells. FASEB JOURNAL, 26. Retrieved from https://www.webofscience.com/

Kennedy, P. C., Zhu, R., Macdonald, T. L., & Lynch, K. R. (2008). Characterization of a Sphingosine-1-phosphate Receptor Antagonist. FASEB JOURNAL, 22. Retrieved from https://www.webofscience.com/

Kennedy, A. J., Mathews, T. P., Kharel, Y., Field, S. D., Moyer, M. L., East, J. E., . . . Macdonald, T. L. (2011). Development of Amidine-Based Sphingosine Kinase 1 Nanomolar Inhibitors and Reduction of Sphingosine 1-Phosphate in Human Leukemia Cells. JOURNAL OF MEDICINAL CHEMISTRY, 54(10), 3524-3548. doi:10.1021/jm2001053

Awad, A. S., Rouse, M. D., Khutsishvili, K., Huang, L., Bolton, W. K., Lynch, K. R., & Okusa, M. D. (2011). Chronic sphingosine 1-phosphate 1 receptor activation attenuates early-stage diabetic nephropathy independent of lymphocytes. KIDNEY INTERNATIONAL, 79(10), 1090-1098. doi:10.1038/ki.2010.544

Kharel, Y., Mathews, T. P., Kennedy, A. J., Houck, J. D., Macdonald, T. L., & Lynch, K. R. (2011). A rapid assay for assessment of sphingosine kinase inhibitors and substrates. ANALYTICAL BIOCHEMISTRY, 411(2), 230-235. doi:10.1016/j.ab.2011.01.003

Chun, J., Hla, T., Lynch, K. R., Spiegel, S., & Moolenaar, W. H. (2010). International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid Receptor Nomenclature. PHARMACOLOGICAL REVIEWS, 62(4), 579-587. doi:10.1124/pr.110.003111

Sefcik, L. S., Aronin, C. E. P., Awojoodu, A. O., Shin, S. J., Mac Gabhann, F., MacDonald, T. L., . . . Botchwey, E. A. (2011). Selective Activation of Sphingosine 1-Phosphate Receptors 1 and 3 Promotes Local Microvascular Network Growth. TISSUE ENGINEERING PART A, 17(5-6), 617-629. doi:10.1089/ten.tea.2010.0404

Aronin, C. E. P., Sefcik, L. S., Tholpady, S. S., Tholpady, A., Sadik, K. W., Macdonald, T. L., . . . Botchwey, E. A. (2010). FTY720 Promotes Local Microvascular Network Formation and Regeneration of Cranial Bone Defects. TISSUE ENGINEERING PART A, 16(6), 1801-1809. doi:10.1089/ten.tea.2009.0539

Derecki, N. C., Cardani, A. N., Yang, C. H., Quinnies, K. M., Crihfield, A., Lynch, K. R., & Kipnis, J. (2010). Regulation of learning and memory by meningeal immunity: a key role for IL-4. JOURNAL OF EXPERIMENTAL MEDICINE, 207(5), 1067-1080. doi:10.1084/jem.20091419

Mathews, T. P., Kennedy, A. J., Kharel, Y., Kennedy, P. C., Nicoara, O., Sunkara, M., . . . Macdonald, T. L. (2010). Discovery, Biological Evaluation, and Structure-Activity Relationship of Amidine Based Sphingosine Kinase Inhibitors. JOURNAL OF MEDICINAL CHEMISTRY, 53(7), 2766-2778. doi:10.1021/jm901860h

Bajwa, A., Jo, S. -K., Ye, H., Huang, L., Dondeti, K. R., Rosin, D. L., . . . Okusa, M. D. (2010). Activation of Sphingosine-1-Phosphate 1 Receptor in the Proximal Tubule Protects Against Ischemia-Reperfusion Injury. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 21(6), 955-965. doi:10.1681/ASN.2009060662

Ma, B., Guckian, K. M., Lin, E. Y. -S., Lee, W. -C., Scott, D., Kumaravel, G., . . . Yang, C. (2010). Stereochemistry-activity relationship of orally active tetralin S1P agonist prodrugs. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 20(7), 2264-2269. doi:10.1016/j.bmcl.2010.02.006

Derecki, N., Cardani, A., Quinnies, K., Crihfield, A., Lynch, K., & Kipnis, J. (2010). Meningeal Immunity, Learning and Memory, and IL-4: Do T cells Make You Smart?. JOURNAL OF IMMUNOLOGY, 184. Retrieved from https://www.webofscience.com/

Wamhoff, B. R., Matthews, T., Hogan, J., Morris, A., Karel, Y., Macdonald, T., & Lynch, K. R. (2010). Sphingosine kinase 1 is required for smooth muscle cell phenotypic modulation in response to vascular injury.. FASEB JOURNAL, 24. Retrieved from https://www.webofscience.com/

Bajwa, A., Jo, S. -K., Ye, H., Huang, L., Dondeti, K. R., Rosin, D. L., . . . Okusa, M. D. (2010). ACTIVATION OF PROXIMAL TUBULE SPIIINGOSINE 1-PHOSPHATE RECEPTOR 1 PROTECTS KIDNEYS FROM ISCHEMIA REPERFUSION INJURY INDEPENDENT OF LYMPHOCYTES. AMERICAN JOURNAL OF KIDNEY DISEASES, 55(4), A42. Retrieved from https://www.webofscience.com/