A Review Discussing Synthesis and Translational Studies of Medicinal Agents Targeting Sphingolipid Pathways
Sphingolipids (SLs) are a class of bioactive lipids characterized by sphingoid bases (SBs) as their backbone structure. These molecules exhibit distinct cellular functions, including cell growth, apoptosis, senescence, migration, and inflammatory responses, by interacting with esterases, amidases, k...
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MDPI AG
2025-07-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/15/7/1022 |
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| author | Sameena Mateen Jordan Oman Soha Haniyyah Kavita Sharma Ali Aghazadeh-Habashi Srinath Pashikanti |
| author_facet | Sameena Mateen Jordan Oman Soha Haniyyah Kavita Sharma Ali Aghazadeh-Habashi Srinath Pashikanti |
| author_sort | Sameena Mateen |
| collection | DOAJ |
| description | Sphingolipids (SLs) are a class of bioactive lipids characterized by sphingoid bases (SBs) as their backbone structure. These molecules exhibit distinct cellular functions, including cell growth, apoptosis, senescence, migration, and inflammatory responses, by interacting with esterases, amidases, kinases, phosphatases, and membrane receptors. These interactions result in a highly interconnected network of enzymes and pathways, known as the sphingolipidome. Dysregulation within this network is implicated in the onset and progression of cardiovascular diseases, metabolic disorders, neurodegenerative disorders, autoimmune diseases, and various cancers. This review highlights the pharmacologically significant sphingoid-based medicinal agents in preclinical and clinical studies. These include myriocin, fingolimod, fenretinide, safingol, spisulosine (ES-285), jaspine B, D-e-MAPP, B13, and α-galactosylceramide. It covers enantioselective syntheses, drug development efforts, and advances in molecular modeling to facilitate an understanding of the binding interactions of these compounds with their biological targets. This review provides a comprehensive evaluation of chiral pool synthetic strategies, translational studies, and the pharmacological relevance of sphingolipid-based drug candidates, offering a pathway for future research in sphingolipid-based therapeutic development. |
| format | Article |
| id | doaj-art-81d789eaa89b4659a98cd1a4fe92ed8b |
| institution | DOAJ |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-81d789eaa89b4659a98cd1a4fe92ed8b2025-08-20T03:08:05ZengMDPI AGBiomolecules2218-273X2025-07-01157102210.3390/biom15071022A Review Discussing Synthesis and Translational Studies of Medicinal Agents Targeting Sphingolipid PathwaysSameena Mateen0Jordan Oman1Soha Haniyyah2Kavita Sharma3Ali Aghazadeh-Habashi4Srinath Pashikanti5Biomedical and Pharmaceutical Sciences Department, Kasiska Division of Health Sciences, L.S. Skaggs College of Pharmacy, Idaho State University, Pocatello, ID 83209-8288, USABiomedical and Pharmaceutical Sciences Department, Kasiska Division of Health Sciences, L.S. Skaggs College of Pharmacy, Idaho State University, Pocatello, ID 83209-8288, USABiomedical and Pharmaceutical Sciences Department, Kasiska Division of Health Sciences, L.S. Skaggs College of Pharmacy, Idaho State University, Pocatello, ID 83209-8288, USABiomedical and Pharmaceutical Sciences Department, Kasiska Division of Health Sciences, L.S. Skaggs College of Pharmacy, Idaho State University, Pocatello, ID 83209-8288, USABiomedical and Pharmaceutical Sciences Department, Kasiska Division of Health Sciences, L.S. Skaggs College of Pharmacy, Idaho State University, Pocatello, ID 83209-8288, USABiomedical and Pharmaceutical Sciences Department, Kasiska Division of Health Sciences, L.S. Skaggs College of Pharmacy, Idaho State University, Pocatello, ID 83209-8288, USASphingolipids (SLs) are a class of bioactive lipids characterized by sphingoid bases (SBs) as their backbone structure. These molecules exhibit distinct cellular functions, including cell growth, apoptosis, senescence, migration, and inflammatory responses, by interacting with esterases, amidases, kinases, phosphatases, and membrane receptors. These interactions result in a highly interconnected network of enzymes and pathways, known as the sphingolipidome. Dysregulation within this network is implicated in the onset and progression of cardiovascular diseases, metabolic disorders, neurodegenerative disorders, autoimmune diseases, and various cancers. This review highlights the pharmacologically significant sphingoid-based medicinal agents in preclinical and clinical studies. These include myriocin, fingolimod, fenretinide, safingol, spisulosine (ES-285), jaspine B, D-e-MAPP, B13, and α-galactosylceramide. It covers enantioselective syntheses, drug development efforts, and advances in molecular modeling to facilitate an understanding of the binding interactions of these compounds with their biological targets. This review provides a comprehensive evaluation of chiral pool synthetic strategies, translational studies, and the pharmacological relevance of sphingolipid-based drug candidates, offering a pathway for future research in sphingolipid-based therapeutic development.https://www.mdpi.com/2218-273X/15/7/1022sphingolipidsnatural productsceramidechiral poolenantioselective synthesis |
| spellingShingle | Sameena Mateen Jordan Oman Soha Haniyyah Kavita Sharma Ali Aghazadeh-Habashi Srinath Pashikanti A Review Discussing Synthesis and Translational Studies of Medicinal Agents Targeting Sphingolipid Pathways Biomolecules sphingolipids natural products ceramide chiral pool enantioselective synthesis |
| title | A Review Discussing Synthesis and Translational Studies of Medicinal Agents Targeting Sphingolipid Pathways |
| title_full | A Review Discussing Synthesis and Translational Studies of Medicinal Agents Targeting Sphingolipid Pathways |
| title_fullStr | A Review Discussing Synthesis and Translational Studies of Medicinal Agents Targeting Sphingolipid Pathways |
| title_full_unstemmed | A Review Discussing Synthesis and Translational Studies of Medicinal Agents Targeting Sphingolipid Pathways |
| title_short | A Review Discussing Synthesis and Translational Studies of Medicinal Agents Targeting Sphingolipid Pathways |
| title_sort | review discussing synthesis and translational studies of medicinal agents targeting sphingolipid pathways |
| topic | sphingolipids natural products ceramide chiral pool enantioselective synthesis |
| url | https://www.mdpi.com/2218-273X/15/7/1022 |
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