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Design, Synthesis, and Anti-leukemic Activity of Stereochemically Defined Constrained Analogs of FTY720 (Gilenya).

ACS medicinal chemistry letters

Fransson R, McCracken AN, Chen B, McMonigle RJ, Edinger AL, Hanessian S.
PMID: 24273632
ACS Med Chem Lett. 2013 Oct 10;4(10). doi: 10.1021/ml4002425.

FTY720 functions as an immunosuppressant due to its effect on sphingosine-1-phosphate receptors. At doses well above those needed for immunosuppression, FTY720 also has anti-neoplastic actions. Our published work suggests that at least some of FTY720's anti-cancer activity is independent...

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Fransson R, McCracken AN, Chen B, et al. Design, Synthesis, and Anti-leukemic Activity of Stereochemically Defined Constrained Analogs of FTY720 (Gilenya). ACS Med Chem Lett. 2013;4(10)doi: 10.1021/ml4002425.
Fransson, R., McCracken, A. N., Chen, B., McMonigle, R. J., Edinger, A. L., & Hanessian, S. (2013). Design, Synthesis, and Anti-leukemic Activity of Stereochemically Defined Constrained Analogs of FTY720 (Gilenya). ACS medicinal chemistry letters, 4(10), . https://doi.org/10.1021/ml4002425
Fransson, Rebecca, et al. "Design, Synthesis, and Anti-leukemic Activity of Stereochemically Defined Constrained Analogs of FTY720 (Gilenya)." ACS medicinal chemistry letters vol. 4,10 (2013). doi: https://doi.org/10.1021/ml4002425
Fransson R, McCracken AN, Chen B, McMonigle RJ, Edinger AL, Hanessian S. Design, Synthesis, and Anti-leukemic Activity of Stereochemically Defined Constrained Analogs of FTY720 (Gilenya). ACS Med Chem Lett. 2013 Oct 10;4(10). doi: 10.1021/ml4002425. PMID: 24273632; PMCID: PMC3834958.
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Berberine ameliorates erectile dysfunction in rats with streptozotocin-induced diabetes mellitus through the attenuation of apoptosis by inhibiting the SPHK1/S1P/S1PR2 and MAPK pathways.

Andrology

Liu K, Sun T, Luan Y, Chen Y, Song J, Ling L, Yuan P, Li R, Cui K, Ruan Y, Lan R, Wang T, Wang S, Liu J, Rao K.
PMID: 34674380
Andrology. 2021 Oct 21; doi: 10.1111/andr.13119. Epub 2021 Oct 21.

BACKGROUND: The population with diabetes mellitus-induced erectile dysfunction is increasing rapidly, but current drugs are not effective in treating erectile dysfunction. Studies of the traditional Chinese medicine extract berberine on diabetes and its complications provide us with new ideas.OBJECTIVES:...

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Liu K, Sun T, Luan Y, et al. Berberine ameliorates erectile dysfunction in rats with streptozotocin-induced diabetes mellitus through the attenuation of apoptosis by inhibiting the SPHK1/S1P/S1PR2 and MAPK pathways. Andrology. 2021;doi: 10.1111/andr.13119.
Liu, K., Sun, T., Luan, Y., Chen, Y., Song, J., Ling, L., Yuan, P., Li, R., Cui, K., Ruan, Y., Lan, R., Wang, T., Wang, S., Liu, J., & Rao, K. (2021). Berberine ameliorates erectile dysfunction in rats with streptozotocin-induced diabetes mellitus through the attenuation of apoptosis by inhibiting the SPHK1/S1P/S1PR2 and MAPK pathways. Andrology, . https://doi.org/10.1111/andr.13119
Liu, Kang, et al. "Berberine ameliorates erectile dysfunction in rats with streptozotocin-induced diabetes mellitus through the attenuation of apoptosis by inhibiting the SPHK1/S1P/S1PR2 and MAPK pathways." Andrology vol. (2021). doi: https://doi.org/10.1111/andr.13119
Liu K, Sun T, Luan Y, Chen Y, Song J, Ling L, Yuan P, Li R, Cui K, Ruan Y, Lan R, Wang T, Wang S, Liu J, Rao K. Berberine ameliorates erectile dysfunction in rats with streptozotocin-induced diabetes mellitus through the attenuation of apoptosis by inhibiting the SPHK1/S1P/S1PR2 and MAPK pathways. Andrology. 2021 Oct 21; doi: 10.1111/andr.13119. Epub 2021 Oct 21. PMID: 34674380.
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Blood-thirsty: S1PR5 and TRM.

The Journal of experimental medicine

Hallisey VM, Schwab SR.
PMID: 34714328
J Exp Med. 2022 Jan 03;219(1). doi: 10.1084/jem.20211971. Epub 2021 Oct 29.

In this elegant study, Evrard et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20210116) find that sphingosine 1-phosphate receptor 5 (S1PR5) powerfully impairs tissue-resident memory T cell (TRM) formation, and that tissue-derived TGF-β limits S1pr5 expression by infiltrating T cells.

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Hallisey VM, Schwab SR. Blood-thirsty: S1PR5 and TRM. J Exp Med. 2021;219(1)doi: 10.1084/jem.20211971.
Hallisey, V. M., & Schwab, S. R. (2022). Blood-thirsty: S1PR5 and TRM. The Journal of experimental medicine, 219(1), . https://doi.org/10.1084/jem.20211971
Hallisey, Victoria M, and Schwab, Susan R. "Blood-thirsty: S1PR5 and TRM." The Journal of experimental medicine vol. 219,1 (2022). doi: https://doi.org/10.1084/jem.20211971
Hallisey VM, Schwab SR. Blood-thirsty: S1PR5 and TRM. J Exp Med. 2022 Jan 03;219(1). doi: 10.1084/jem.20211971. Epub 2021 Oct 29. PMID: 34714328; PMCID: PMC8574975.
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Blood-thirsty: S1PR5 and TRM.

The Journal of experimental medicine

Hallisey VM, Schwab SR.
PMID: 34714328
J Exp Med. 2022 Jan 03;219(1). doi: 10.1084/jem.20211971. Epub 2021 Oct 29.

In this elegant study, Evrard et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20210116) find that sphingosine 1-phosphate receptor 5 (S1PR5) powerfully impairs tissue-resident memory T cell (TRM) formation, and that tissue-derived TGF-β limits S1pr5 expression by infiltrating T cells.

Cite
Hallisey VM, Schwab SR. Blood-thirsty: S1PR5 and TRM. J Exp Med. 2021;219(1)doi: 10.1084/jem.20211971.
Hallisey, V. M., & Schwab, S. R. (2022). Blood-thirsty: S1PR5 and TRM. The Journal of experimental medicine, 219(1), . https://doi.org/10.1084/jem.20211971
Hallisey, Victoria M, and Schwab, Susan R. "Blood-thirsty: S1PR5 and TRM." The Journal of experimental medicine vol. 219,1 (2022). doi: https://doi.org/10.1084/jem.20211971
Hallisey VM, Schwab SR. Blood-thirsty: S1PR5 and TRM. J Exp Med. 2022 Jan 03;219(1). doi: 10.1084/jem.20211971. Epub 2021 Oct 29. PMID: 34714328; PMCID: PMC8574975.
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Gene Pair Correlation Coefficients in Sphingolipid Metabolic Pathway as a Potential Prognostic Biomarker for Breast Cancer.

Cancers

Sakharkar MK, Kaur Dhillon S, Chidambaram SB, Essa MM, Yang J.
PMID: 32630169
Cancers (Basel). 2020 Jul 01;12(7). doi: 10.3390/cancers12071747.

Complex diseases such as cancer are usually governed by dynamic and simultaneous modifications of multiple genes. Since sphingolipids are potent bioactive molecules and regulate many important pathophysiological processes such as carcinogenesis, we studied the gene pair correlations of 36...

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Sakharkar MK, Kaur Dhillon S, Chidambaram SB, et al. Gene Pair Correlation Coefficients in Sphingolipid Metabolic Pathway as a Potential Prognostic Biomarker for Breast Cancer. Cancers (Basel). 2020;12(7)doi: 10.3390/cancers12071747.
Sakharkar, M. K., Kaur Dhillon, S., Chidambaram, S. B., Essa, M. M., & Yang, J. (2020). Gene Pair Correlation Coefficients in Sphingolipid Metabolic Pathway as a Potential Prognostic Biomarker for Breast Cancer. Cancers, 12(7), . https://doi.org/10.3390/cancers12071747
Sakharkar, Meena Kishore, et al. "Gene Pair Correlation Coefficients in Sphingolipid Metabolic Pathway as a Potential Prognostic Biomarker for Breast Cancer." Cancers vol. 12,7 (2020). doi: https://doi.org/10.3390/cancers12071747
Sakharkar MK, Kaur Dhillon S, Chidambaram SB, Essa MM, Yang J. Gene Pair Correlation Coefficients in Sphingolipid Metabolic Pathway as a Potential Prognostic Biomarker for Breast Cancer. Cancers (Basel). 2020 Jul 01;12(7). doi: 10.3390/cancers12071747. PMID: 32630169; PMCID: PMC7409333.
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Sphingolipids in Lung Pathology in the Coronavirus Disease Era: A Review of Sphingolipid Involvement in the Pathogenesis of Lung Damage.

Frontiers in physiology

Khan SA, Goliwas KF, Deshane JS.
PMID: 34690821
Front Physiol. 2021 Oct 08;12:760638. doi: 10.3389/fphys.2021.760638. eCollection 2021.

Sphingolipids are bioactive lipids involved in the regulation of cell survival, proliferation, and the inflammatory response. The SphK/S1P/S1PR pathway (S1P pathway) is a driver of many anti-apoptotic and proliferative processes. Pro-survival sphingolipid sphingosine-1-phosphate (S1P) initiates its signaling cascade by...

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Khan SA, Goliwas KF, Deshane JS. Sphingolipids in Lung Pathology in the Coronavirus Disease Era: A Review of Sphingolipid Involvement in the Pathogenesis of Lung Damage. Front Physiol. 2021;12:760638doi: 10.3389/fphys.2021.760638.
Khan, S. A., Goliwas, K. F., & Deshane, J. S. (2021). Sphingolipids in Lung Pathology in the Coronavirus Disease Era: A Review of Sphingolipid Involvement in the Pathogenesis of Lung Damage. Frontiers in physiology, 12760638. https://doi.org/10.3389/fphys.2021.760638
Khan, Saad A, et al. "Sphingolipids in Lung Pathology in the Coronavirus Disease Era: A Review of Sphingolipid Involvement in the Pathogenesis of Lung Damage." Frontiers in physiology vol. 12 (2021): 760638. doi: https://doi.org/10.3389/fphys.2021.760638
Khan SA, Goliwas KF, Deshane JS. Sphingolipids in Lung Pathology in the Coronavirus Disease Era: A Review of Sphingolipid Involvement in the Pathogenesis of Lung Damage. Front Physiol. 2021 Oct 08;12:760638. doi: 10.3389/fphys.2021.760638. eCollection 2021. PMID: 34690821; PMCID: PMC8531546.
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Sphingosine kinase 1 inhibition improves lipopolysaccharide/D-galactosamine-induced acute liver failure by inhibiting mitogen-activated protein kinases pathway.

United European gastroenterology journal

Tian T, Tian W, Yang F, Zhao R, Huang Q, Zhao Y.
PMID: 27733910
United European Gastroenterol J. 2016 Oct;4(5):677-685. doi: 10.1177/2050640616637968. Epub 2016 Mar 02.

BACKGROUND: Sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P)/sphingosine-1-phosphate receptors (S1PRs) signaling plays a key role in inflammatory responses. Lei et al. showed that SphK1 inhibition presented a hepatoprotective effect on acute liver damage via decreasing hepatic high-mobility group box 1 (HMGB1)...

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Tian T, Tian W, Yang F, et al. Sphingosine kinase 1 inhibition improves lipopolysaccharide/D-galactosamine-induced acute liver failure by inhibiting mitogen-activated protein kinases pathway. United European Gastroenterol J. 2016;4(5):677-685doi: 10.1177/2050640616637968.
Tian, T., Tian, W., Yang, F., Zhao, R., Huang, Q., & Zhao, Y. (2016). Sphingosine kinase 1 inhibition improves lipopolysaccharide/D-galactosamine-induced acute liver failure by inhibiting mitogen-activated protein kinases pathway. United European gastroenterology journal, 4(5), 677-685. https://doi.org/10.1177/2050640616637968
Tian, Tao, et al. "Sphingosine kinase 1 inhibition improves lipopolysaccharide/D-galactosamine-induced acute liver failure by inhibiting mitogen-activated protein kinases pathway." United European gastroenterology journal vol. 4,5 (2016): 677-685. doi: https://doi.org/10.1177/2050640616637968
Tian T, Tian W, Yang F, Zhao R, Huang Q, Zhao Y. Sphingosine kinase 1 inhibition improves lipopolysaccharide/D-galactosamine-induced acute liver failure by inhibiting mitogen-activated protein kinases pathway. United European Gastroenterol J. 2016 Oct;4(5):677-685. doi: 10.1177/2050640616637968. Epub 2016 Mar 02. PMID: 27733910; PMCID: PMC5042311.
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To stay or to leave: Stem cells and progenitor cells navigating the S1P gradient.

World journal of biological chemistry

Liu J, Hsu A, Lee JF, Cramer DE, Lee MJ.
PMID: 21472036
World J Biol Chem. 2011 Jan 26;2(1):1-13. doi: 10.4331/wjbc.v2.i1.1.

Most hematopoietic stem progenitor cells (HSPCs) reside in bone marrow (BM), but a small amount of HSPCs have been found to circulate between BM and tissues through blood and lymph. Several lines of evidence suggest that sphingosine-1-phosphate (S1P) gradient...

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Liu J, Hsu A, Lee JF, et al. To stay or to leave: Stem cells and progenitor cells navigating the S1P gradient. World J Biol Chem. 2011;2(1):1-13doi: 10.4331/wjbc.v2.i1.1.
Liu, J., Hsu, A., Lee, J. F., Cramer, D. E., & Lee, M. J. (2011). To stay or to leave: Stem cells and progenitor cells navigating the S1P gradient. World journal of biological chemistry, 2(1), 1-13. https://doi.org/10.4331/wjbc.v2.i1.1
Liu, Jingjing, et al. "To stay or to leave: Stem cells and progenitor cells navigating the S1P gradient." World journal of biological chemistry vol. 2,1 (2011): 1-13. doi: https://doi.org/10.4331/wjbc.v2.i1.1
Liu J, Hsu A, Lee JF, Cramer DE, Lee MJ. To stay or to leave: Stem cells and progenitor cells navigating the S1P gradient. World J Biol Chem. 2011 Jan 26;2(1):1-13. doi: 10.4331/wjbc.v2.i1.1. PMID: 21472036; PMCID: PMC3070303.
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Sphingosine 1-Phosphate Receptors and Metabolic Enzymes as Druggable Targets for Brain Diseases.

Frontiers in pharmacology

Grassi S, Mauri L, Prioni S, Cabitta L, Sonnino S, Prinetti A, Giussani P.
PMID: 31427962
Front Pharmacol. 2019 Jul 23;10:807. doi: 10.3389/fphar.2019.00807. eCollection 2019.

The central nervous system is characterized by a high content of sphingolipids and by a high diversity in terms of different structures. Stage- and cell-specific sphingolipid metabolism and expression are crucial for brain development and maintenance toward adult age....

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Grassi S, Mauri L, Prioni S, et al. Sphingosine 1-Phosphate Receptors and Metabolic Enzymes as Druggable Targets for Brain Diseases. Front Pharmacol. 2019;10:807doi: 10.3389/fphar.2019.00807.
Grassi, S., Mauri, L., Prioni, S., Cabitta, L., Sonnino, S., Prinetti, A., & Giussani, P. (2019). Sphingosine 1-Phosphate Receptors and Metabolic Enzymes as Druggable Targets for Brain Diseases. Frontiers in pharmacology, 10807. https://doi.org/10.3389/fphar.2019.00807
Grassi, Sara, et al. "Sphingosine 1-Phosphate Receptors and Metabolic Enzymes as Druggable Targets for Brain Diseases." Frontiers in pharmacology vol. 10 (2019): 807. doi: https://doi.org/10.3389/fphar.2019.00807
Grassi S, Mauri L, Prioni S, Cabitta L, Sonnino S, Prinetti A, Giussani P. Sphingosine 1-Phosphate Receptors and Metabolic Enzymes as Druggable Targets for Brain Diseases. Front Pharmacol. 2019 Jul 23;10:807. doi: 10.3389/fphar.2019.00807. eCollection 2019. PMID: 31427962; PMCID: PMC6689979.
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Roles of G Protein-Coupled Receptors (GPCRs) in Gastrointestinal Cancers: Focus on Sphingosine 1-Shosphate Receptors, Angiotensin II Receptors, and Estrogen-Related GPCRs.

Cells

Zeng Z, Ma C, Chen K, Jiang M, Vasu R, Liu R, Zhao Y, Zhang H.
PMID: 34831211
Cells. 2021 Nov 03;10(11). doi: 10.3390/cells10112988.

It is well established that gastrointestinal (GI) cancers are common and devastating diseases around the world. Despite the significant progress that has been made in the treatment of GI cancers, the mortality rates remain high, indicating a real need...

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Zeng Z, Ma C, Chen K, et al. Roles of G Protein-Coupled Receptors (GPCRs) in Gastrointestinal Cancers: Focus on Sphingosine 1-Shosphate Receptors, Angiotensin II Receptors, and Estrogen-Related GPCRs. Cells. 2021;10(11)doi: 10.3390/cells10112988.
Zeng, Z., Ma, C., Chen, K., Jiang, M., Vasu, R., Liu, R., Zhao, Y., & Zhang, H. (2021). Roles of G Protein-Coupled Receptors (GPCRs) in Gastrointestinal Cancers: Focus on Sphingosine 1-Shosphate Receptors, Angiotensin II Receptors, and Estrogen-Related GPCRs. Cells, 10(11), . https://doi.org/10.3390/cells10112988
Zeng, Zhen, et al. "Roles of G Protein-Coupled Receptors (GPCRs) in Gastrointestinal Cancers: Focus on Sphingosine 1-Shosphate Receptors, Angiotensin II Receptors, and Estrogen-Related GPCRs." Cells vol. 10,11 (2021). doi: https://doi.org/10.3390/cells10112988
Zeng Z, Ma C, Chen K, Jiang M, Vasu R, Liu R, Zhao Y, Zhang H. Roles of G Protein-Coupled Receptors (GPCRs) in Gastrointestinal Cancers: Focus on Sphingosine 1-Shosphate Receptors, Angiotensin II Receptors, and Estrogen-Related GPCRs. Cells. 2021 Nov 03;10(11). doi: 10.3390/cells10112988. PMID: 34831211; PMCID: PMC8616429.
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Berberine ameliorates erectile dysfunction in rats with streptozotocin-induced diabetes mellitus through the attenuation of apoptosis by inhibiting the SPHK1/S1P/S1PR2 and MAPK pathways.

Andrology

Liu K, Sun T, Luan Y, Chen Y, Song J, Ling L, Yuan P, Li R, Cui K, Ruan Y, Lan R, Wang T, Wang S, Liu J, Rao K.
PMID: 34674380
Andrology. 2022 Feb;10(2):404-418. doi: 10.1111/andr.13119. Epub 2021 Oct 27.

BACKGROUND: The population with diabetes mellitus-induced erectile dysfunction is increasing rapidly, but current drugs are not effective in treating erectile dysfunction. Studies of the traditional Chinese medicine extract berberine on diabetes and its complications provide us with new ideas.OBJECTIVES:...

Cite
Liu K, Sun T, Luan Y, et al. Berberine ameliorates erectile dysfunction in rats with streptozotocin-induced diabetes mellitus through the attenuation of apoptosis by inhibiting the SPHK1/S1P/S1PR2 and MAPK pathways. Andrology. 2021;10(2):404-418doi: 10.1111/andr.13119.
Liu, K., Sun, T., Luan, Y., Chen, Y., Song, J., Ling, L., Yuan, P., Li, R., Cui, K., Ruan, Y., Lan, R., Wang, T., Wang, S., Liu, J., & Rao, K. (2022). Berberine ameliorates erectile dysfunction in rats with streptozotocin-induced diabetes mellitus through the attenuation of apoptosis by inhibiting the SPHK1/S1P/S1PR2 and MAPK pathways. Andrology, 10(2), 404-418. https://doi.org/10.1111/andr.13119
Liu, Kang, et al. "Berberine ameliorates erectile dysfunction in rats with streptozotocin-induced diabetes mellitus through the attenuation of apoptosis by inhibiting the SPHK1/S1P/S1PR2 and MAPK pathways." Andrology vol. 10,2 (2022): 404-418. doi: https://doi.org/10.1111/andr.13119
Liu K, Sun T, Luan Y, Chen Y, Song J, Ling L, Yuan P, Li R, Cui K, Ruan Y, Lan R, Wang T, Wang S, Liu J, Rao K. Berberine ameliorates erectile dysfunction in rats with streptozotocin-induced diabetes mellitus through the attenuation of apoptosis by inhibiting the SPHK1/S1P/S1PR2 and MAPK pathways. Andrology. 2022 Feb;10(2):404-418. doi: 10.1111/andr.13119. Epub 2021 Oct 27. PMID: 34674380.
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Deconstructing the Pharmacological Contribution of Sphingosine-1 Phosphate Receptors to Mouse Models of Multiple Sclerosis Using the Species Selectivity of Ozanimod, a Dual Modulator of Human Sphingosine 1-Phosphate Receptor Subtypes 1 and 5.

The Journal of pharmacology and experimental therapeutics

Selkirk JV, Dines KC, Yan YG, Ching N, Dalvie D, Biswas S, Bortolato A, Schkeryantz JM, Lopez C, Ruiz I, Hargreaves R.
PMID: 34535564
J Pharmacol Exp Ther. 2021 Dec;379(3):386-399. doi: 10.1124/jpet.121.000741. Epub 2021 Sep 17.

Ozanimod, a sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity selectively to S1P receptor subtypes 1 (S1P

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Selkirk JV, Dines KC, Yan YG, et al. Deconstructing the Pharmacological Contribution of Sphingosine-1 Phosphate Receptors to Mouse Models of Multiple Sclerosis Using the Species Selectivity of Ozanimod, a Dual Modulator of Human Sphingosine 1-Phosphate Receptor Subtypes 1 and 5. J Pharmacol Exp Ther. 2021;379(3):386-399doi: 10.1124/jpet.121.000741.
Selkirk, J. V., Dines, K. C., Yan, Y. G., Ching, N., Dalvie, D., Biswas, S., Bortolato, A., Schkeryantz, J. M., Lopez, C., Ruiz, I., & Hargreaves, R. (2021). Deconstructing the Pharmacological Contribution of Sphingosine-1 Phosphate Receptors to Mouse Models of Multiple Sclerosis Using the Species Selectivity of Ozanimod, a Dual Modulator of Human Sphingosine 1-Phosphate Receptor Subtypes 1 and 5. The Journal of pharmacology and experimental therapeutics, 379(3), 386-399. https://doi.org/10.1124/jpet.121.000741
Selkirk, Julie V, et al. "Deconstructing the Pharmacological Contribution of Sphingosine-1 Phosphate Receptors to Mouse Models of Multiple Sclerosis Using the Species Selectivity of Ozanimod, a Dual Modulator of Human Sphingosine 1-Phosphate Receptor Subtypes 1 and 5." The Journal of pharmacology and experimental therapeutics vol. 379,3 (2021): 386-399. doi: https://doi.org/10.1124/jpet.121.000741
Selkirk JV, Dines KC, Yan YG, Ching N, Dalvie D, Biswas S, Bortolato A, Schkeryantz JM, Lopez C, Ruiz I, Hargreaves R. Deconstructing the Pharmacological Contribution of Sphingosine-1 Phosphate Receptors to Mouse Models of Multiple Sclerosis Using the Species Selectivity of Ozanimod, a Dual Modulator of Human Sphingosine 1-Phosphate Receptor Subtypes 1 and 5. J Pharmacol Exp Ther. 2021 Dec;379(3):386-399. doi: 10.1124/jpet.121.000741. Epub 2021 Sep 17. PMID: 34535564.
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