Fingolimod (FTY720): First approved oral therapy for multiple sclerosis

Sharma, Sushil; Mathur, AG; Pradhan, Sapna; Singh, D. B.; Gupta, Shantanu

doi:10.4103/0976-500x.77118

Cited by 62 publications

(64 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is noted that the therapeutic FTY720 doses (of 5–10 mg/kg) that we and others have used in animal cancer models (50,51) are higher (by fold 10) than that used in models of cerebral ischemia (52,53) or multiple sclerosis (54). FTY720 treatment is associated with adverse effects that include headache, influenza-like illness, fatigue, gastrointestinal dysfunction, hemorrhaging focal encephalitis as well as transient bradycardia, and skin cancer (55).…”

Section: Discussionmentioning

confidence: 88%

Sphingosine-1-Phosphate Receptor-1 Promotes Environment-Mediated and Acquired Chemoresistance

Lifshitz

Priceman

et al. 2017

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Drug resistance is a major barrier for the development of effective and durable cancer therapies. Overcoming this challenge requires further defining the cellular and molecular mechanisms underlying drug resistance, both acquired and environment-mediated drug resistance (EMDR). Here, using neuroblastoma (NB), a childhood cancer with high incidence of recurrence due to resistance to chemotherapy, as a model we show that human bone marrow-mesenchymal stromal cells induce tumor expression of sphingosine-1-phosphate receptor-1 (S1PR1) leading to their resistance to chemotherapy. Targeting S1PR1 by shRNA markedly enhances etoposide-induced apoptosis in NB cells and abrogates EMDR, while over-expression of S1PR1 significantly protects NB cells from multidrug-induced apoptosis via activating JAK-STAT3 signaling. Elevated S1PR1 expression and STAT3 activation are also observed in human NB cells with acquired resistance to etoposide. We show in vitro and in human NB xenograft models that treatment with FTY720, an FDA-approved drug and antagonist of S1PR1, dramatically sensitizes drug-resistant cells to etoposide. In summary, we identify S1PR1 as a critical target for reducing both EMDR and acquired chemoresistance in NB.

show abstract

Section: Discussionmentioning

confidence: 88%

Sphingosine-1-Phosphate Receptor-1 Promotes Environment-Mediated and Acquired Chemoresistance

Lifshitz

Priceman

et al. 2017

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…Successful development of the sphingosine analogue FTY720, a pro-S1P mimetic, as a valuable drug has been established. FTY720 has been approved by FDA for the treatment of relapsing multiple sclerosis [80]. Inhibitors of S1P metabolism and its receptors have proven effective in many animal models of human diseases [81].…”

Section: Resultsmentioning

confidence: 99%

Regulation of Mitochondrial Function by Bioactive Sphingolipids

Nema¹

2015

View full text Add to dashboard Cite

Sphingolipids such as ceramide, sphingosine and sphingosine 1 cellular functions. Sphingolipids mediates metabolites play an important role in the development and progression of mitochondria related disorders. as an important second messenger in apoptosis signaling and is generated by de novo synthesis, sphingomyelin hydrolysis, or recycling of sphingolipids. S1P, a potent signaling sphingolipid exerts myriads of pathophysiological function, including lymphocyte trafficking, angiogenesis, vascular development and inflammation. sphingolipids, such as S1P, sphingosine, an respiratory function, apoptosis and calcium homeostasis. Further, we discuss the role of sphingolipids in mitochondrial diseases and targeting them for drug development. in human health and disease.

show abstract

“…Of interest, a liposomal formulation of safingol demonstrated high in vivo antitumor efficacy in acute myeloid leukemia, while limiting adverse effects like hemolysis (Tan et al, 2012). Finally, the success of the FDA-approved orally available FTY720 (Fingolimod) for multiple sclerosis further supports new formulations for oral delivery of sphingoid derivatives for cancer therapy, including Enigmol, an oral sphingolipid analog, [(2S, 3S, 5S)-2-amino-3, 5-dihydroxyoctadecane] (Sharma et al, 2011;Symolon et al, 2011).…”

Section: Introductionmentioning

confidence: 96%

Preclinical development of a C6-ceramide NanoLiposome, a novel sphingolipid therapeutic

Kester¹,

Bassler

Fox

et al. 2015

Biological Chemistry

View full text Add to dashboard Cite

Despite the therapeutic potential of sphingolipids, the ability to develop this class of compounds as active pharmaceutical ingredients has been hampered by issues of solubility and delivery. Beyond these technical hurdles, significant challenges in completing the necessary preclinical studies to support regulatory review are necessary for commercialization. This review seeks to identify the obstacles and potential solutions in the translation of a novel liposomal technology from the academic bench to investigational new drug (IND) stage by discussing the preclinical development of the Ceramide NanoLiposome (CNL), which is currently being developed as an anticancer drug for the initial indication of hepatocellular carcinoma (HCC).

show abstract

Fingolimod (FTY720): First approved oral therapy for multiple sclerosis

Cited by 62 publications

References 19 publications

Sphingosine-1-Phosphate Receptor-1 Promotes Environment-Mediated and Acquired Chemoresistance

Sphingosine-1-Phosphate Receptor-1 Promotes Environment-Mediated and Acquired Chemoresistance

Regulation of Mitochondrial Function by Bioactive Sphingolipids

Preclinical development of a C6-ceramide NanoLiposome, a novel sphingolipid therapeutic

Contact Info

Product

Resources

About