To fingolimod and beyond: The rich pipeline of drug candidates that target S1P signaling.

Abstract:

:Sphingosine 1-phosphate (S1P) is an extracellular lipid signaling molecule that acts as a selective, high-affinity ligand for a family of five G protein-coupled receptors. This signaling system was first identified twenty years ago, and has since been shown to regulate a diverse range of physiological processes and disease states, such as cardiovascular development, immune function, hypoxic responses, and cancer. The therapeutic potential of targeting this system took center stage when it was demonstrated that the immune modulator, fingolimod (FTY720/Gilenya), exerts it lymphopenic effect by acting on S1P receptors, primarily on S1P receptor 1 (S1P1). In 2010, fingolimod became the first oral medication approved for the treatment of multiple sclerosis (MS). Since then, second-generation S1P receptor modulators have been under development in an effort to provide improved safety and efficacy profiles for MS, and to broaden their use to other autoimmune indications. Beyond the development of S1P1-modulators, there has been considerable effort in targeting other components of the S1P signaling pathway for the treatment of other diseases, such as cardiovascular disease, sepsis, and cancer. This manuscript provides an overview of the clinical and preclinical development of drugs targeting S1P signaling.

journal_name

Pharmacol Res

journal_title

Pharmacological research

authors

Chew WS,Wang W,Herr DR

doi

10.1016/j.phrs.2016.09.025

subject

Has Abstract

pub_date

2016-11-01 00:00:00

pages

521-532

issue

Pt A

eissn

1043-6618

issn

1096-1186

pii

S1043-6618(16)30877-5

journal_volume

113

pub_type

杂志文章,评审
  • Effect of nimodipine on systemic, renal, and cerebral haemodynamics after a mild hypoxic-ischaemic insult in newborn piglets.

    abstract::Because many Ca2+ channel blocking agents are known to cause adverse systemic effects, in this study we tested the haemodynamic side effects of nimodipine with and without a mild hypoxic-ischaemic (HI) insult in a newborn piglet model. Fifteen min after completing a brief period of asphyxia we gave i.v. nimodipine as ...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1006/phrs.1996.0002

    authors: Raju TN,John E,Shankararao R,Fornell L,Vasa R,Abu-Harb M

    更新日期:1996-01-01 00:00:00

  • Open questions in bioequivalence.

    abstract::Bioequivalence studies are mainly required to demonstrate the interchangeability of multisource pharmaceutical products, usually called generics. A pivotal investigation projected and conducted in compliance with specific guidelines allows a replicative company to register a generic drug via an ANDA (abbreviated new d...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/s1043-6618(05)80028-3

    authors: Marzo A

    更新日期:1995-10-01 00:00:00

  • Flumazenil, diazepam, nordiazepam and oxazepam interactions on plasma protein binding.

    abstract::The effect of flumazenil (FLU) on plasma protein binding of diazepam (DZ), nordiazepam (ND) and oxazepam (OX) was determined in plasma from drug-naive dogs to which graded concentrations of tested drugs alone and in combination were added. The results revealed that as the concentration of FLU added to plasma alone was...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/s1043-6618(05)80018-0

    authors: Wala EP,Sloan JW

    更新日期:1995-11-01 00:00:00

  • Calumenin and fibulin-1 on tumor metastasis: Implications for pharmacology.

    abstract::Tumor metastasis is a key cause of cancer mortality, and inhibiting migration of cancer cells is one of the major directions of anti-metastatic drug development. Calumenin and fibulin-1 are two extracellular proteins that synergistically inhibit cell migration and tumor metastasis, and could potentially be served as t...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审

    doi:10.1016/j.phrs.2015.05.001

    authors: Zheng P,Wang Q,Teng J,Chen J

    更新日期:2015-09-01 00:00:00

  • Effects of nifedipine and Bay K 8644 on the R-PIA and caffeine-induced changes in the locomotor activity of rats.

    abstract::Possible interaction between adenosine and L type Ca2+ channel in the locomotor activity of rats was investigated. R-PIA (0.05 mg kg-1), an adenosine analogue, and caffeine (20 mg kg-1), an adenosine receptor antagonist, significantly decreased and increased locomotor activity, respectively. Ca2+ channel blocker nifed...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1006/phrs.1996.0021

    authors: Eroglu L,Tuna R,Caglayan B

    更新日期:1996-02-01 00:00:00

  • Tumor deconstruction as a tool for advanced drug screening and repositioning.

    abstract::A major focus of contemporary drug screening strategies is the identification of novel anticancer compounds, which often results in underutilization of resources. Current drug evaluation involves in vivo tumor (xenograft) regression as proof-of-principle for cytotoxicity (POC). However, this end-point lacks any assess...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/j.phrs.2016.07.018

    authors: Naik RR,Luo T,Kohandel M,Bapat SA

    更新日期:2016-09-01 00:00:00

  • NGF topical application in patients with corneal ulcer does not generate circulating NGF antibodies.

    abstract::Nerve growth factor (NGF) is the prototype of the neurotrophin family and promotes the survival of specific populations of neurons, stimulates their morphological differentiation and regulates neuronal gene expression. Since its discovery, NGF attracted clinicians for its potential application in the treatment of neur...

    journal_title:Pharmacological research

    pub_type: 临床试验,杂志文章

    doi:10.1016/j.phrs.2007.03.007

    authors: Lambiase A,Coassin M,Sposato V,Micera A,Sacchetti M,Bonini S,Aloe L

    更新日期:2007-07-01 00:00:00

  • Boosting immunity to treat parasitic infections: Asaia bacteria expressing a protein from Wolbachia determine M1 macrophage activation and killing of Leishmania protozoans.

    abstract::Leishmaniases are severe vector-borne diseases affecting humans and animals, caused by Leishmania protozoans. Over one billion people and millions of dogs live in endemic areas for leishmaniases and are at risk of infection. Immune polarization plays a major role in determining the outcome of Leishmania infections: ho...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/j.phrs.2020.105288

    authors: Varotto-Boccazzi I,Epis S,Arnoldi I,Corbett Y,Gabrieli P,Paroni M,Nodari R,Basilico N,Sacchi L,Gramiccia M,Gradoni L,Tranquillo V,Bandi C

    更新日期:2020-11-01 00:00:00

  • Effects of the methyl esters of pyruvate, succinate and glutamate on the secretory response to meglitinide analogues in rat pancreatic islets.

    abstract::The insulinotropic action of the meglitinide analogues KAD-1229, A-4166 and repaglinide was examined in rat pancreatic islets deprived of exogenous nutrient or incubated in the presence of nutrient secretagogues such as D-glucose and the methyl esters of pyruvic acid, succinic acid and glutamic acid. The meglitinide a...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1006/phrs.1996.0026

    authors: Bakkali Nadi A,Zhang TM,Malaisse WJ

    更新日期:1996-03-01 00:00:00

  • The abundance of the long intergenic non-coding RNA 01087 differentiates between luminal and triple-negative breast cancers and predicts patient outcome.

    abstract::The molecular complexity of human breast cancer (BC) renders the clinical management of the disease challenging. Long non-coding RNAs (lncRNAs) are promising biomarkers for BC patient stratification, early detection, and disease monitoring. Here, we identified the involvement of the long intergenic non-coding RNA 0108...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/j.phrs.2020.105249

    authors: De Palma FDE,Del Monaco V,Pol JG,Kremer M,D'Argenio V,Stoll G,Montanaro D,Uszczyńska-Ratajczak B,Klein CC,Vlasova A,Botti G,D'Aiuto M,Baldi A,Guigó R,Kroemer G,Maiuri MC,Salvatore F

    更新日期:2020-11-01 00:00:00

  • Regulation of endothelin-converting enzyme-1 (ECE-1) by the calcimimetic R-568.

    abstract::Although calcimimetics were developed to block parathyroid hormone synthesis, some reports suggest that they may also reduce blood pressure by unknown mechanisms. Calcimimetic-induced changes in the synthesis of endothelial vasoactive factors could be involved. Wistar rats were treated with the calcimimetic R-568, and...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/j.phrs.2013.07.006

    authors: Martínez-Miguel P,Medrano-Andrés D,Lopes-Martín V,Arribas-Gómez I,Rodríguez-Puyol M,Rodríguez-Puyol D,López-Ongil S

    更新日期:2013-10-01 00:00:00

  • Effects of acetylbergenin against D -galactosamine-induced hepatotoxicity in rats.

    abstract::The hepatoprotective effects of acetylbergenin were examined against D -galactosamine (GalN)-induced liver damage in rats, compared with that of bergenin reported previously. Acetylbergenin was synthesized from acetylation of bergenin, isolated from Mallotus japonicus, to increase lipophilic and physiological activiti...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1006/phrs.2000.0730

    authors: Lim HK,Kim HS,Choi HS,Oh S,Jang CG,Choi J,Kim SH,Chang MJ

    更新日期:2000-11-01 00:00:00

  • Etrolizumab versus infliximab in the treatment of induction phase of ulcerative colitis: A systematic review and indirect comparison.

    abstract:OBJECTIVES:There is still a need to develop new effective medications for the treatment of ulcerative colitis, particularly for patients who are intolerant or resistant to first line therapies. This article compared the efficacy and safety of etrolizumab and infliximab in moderate to severe ulcerative colitis. METHODS...

    journal_title:Pharmacological research

    pub_type: 杂志文章,meta分析

    doi:10.1016/j.phrs.2018.11.003

    authors: Motaghi E,Ghasemi-Pirbaluti M,Zabihi M

    更新日期:2019-01-01 00:00:00

  • Metabolic and renal effects of Laevo-carnitine and propionyl-carnitine in rats with subtotal nephrectomy.

    abstract::The renal and metabolic effects of chronic carnitine administration were evaluated in the early stages of experimentally-induced renal failure. Laevo-carnitine (n = 5), Propionyl-carnitine (n = 5) both at 200 mg kg-1 of body weight, or vehicle (physiological saline solution, 0.4 ml kg-1 body weight, n = 5) were admini...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1006/phrs.1996.0083

    authors: Palomba D,Pes GM,Demontis MP,Varoni MV,Deiana L,Anania V

    更新日期:1996-09-01 00:00:00

  • Effects of antiemetic drugs on glucose 6-phosphate dehydrogenase and some antioxidant enzymes.

    abstract::The aim of this study was to investigate effect of antiemetics on G6PD and antioxidant enzymes. Antiemetics are currently being used to reduce or prevent nausea and vomiting in patients. This is the first study to show effect of antiemetics on glucose-6-phosphate dehydrogenase (G6PD) and antioxidant enzyme activities....

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/j.phrs.2004.05.007

    authors: Ozmen I,Küfrevioglu OI

    更新日期:2004-11-01 00:00:00

  • Effect of indomethacin on the kinetics of tumour necrosis factor alpha release and tumour necrosis factor alpha gene expression by human blood monocytes.

    abstract::In this investigation we have examined the effects of indomethacin, an inhibitor of the cyclooxygenase pathway of arachidonic acid, upon the kinetics of the release of tumour necrosis factor alpha (TNF) and of the expression of TNF gene by lipopolysaccharide (LPS)-stimulated human blood monocytes (BM). Following stimu...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/s1043-6618(05)80084-2

    authors: Spatafora M,Chiappara G,D'Amico D,Volpes D,Melis M,Pace E,Merendino A

    更新日期:1991-04-01 00:00:00

  • Molecular modeling study on resistance of WT/D473H SMO to antagonists LDE-225 and LEQ-506.

    abstract::The smoothened (SMO) receptor, an essential signal transducer in the Hedgehog pathway, was targeted with antagonists to suppress the tumor. It is interesting that SMO D473H mutation confers resistance on inhibitor LDE-225 rather than LEQ-506. In this paper, the binding modes of them against the wild type and mutant SM...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/j.phrs.2017.11.025

    authors: Tu J,Li JJ,Song LT,Zhai HL,Wang J,Zhang XY

    更新日期:2018-03-01 00:00:00

  • DNA microarray analysis of white adipose tissue from obese (fa/fa) Zucker rats treated with a beta3-adrenoceptor agonist, KTO-7924.

    abstract::We aimed to examine the effects of KTO-7924 (beta3-adrenoceptor agonist) on lipid metabolism and mRNA expressions in retroperitoneal white adipose tissue (RP WAT) in obese (fa/fa) Zucker rats using DNA microarray. Oral KTO-7924 for 28 days significantly decreased RP WAT weight, plasma triglyceride, free fatty acid, an...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/j.phrs.2005.05.014

    authors: Oana F,Homma T,Takeda H,Matsuzawa A,Akahane S,Isaji M,Akahane M

    更新日期:2005-11-01 00:00:00

  • Free radicals and antioxidant status following pylorus ligation induced gastric mucosal injury in rats.

    abstract::The present investigation was undertaken to suggest the involvement of free radicals in the pathogenesis of pyloric ligation induced ulcers in rats. Lipid peroxidation product (MDA), antioxidant contents and secretory activity have been studied in the rat stomach at different time intervals after pylorus ligation indu...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1006/phrs.1998.0343

    authors: Rastogi L,Patnaik GK,Dikshit M

    更新日期:1998-08-01 00:00:00

  • N3,N7-diaminophenothiazinium derivatives as antagonists of α7-nicotinic acetylcholine receptors expressed in Xenopus oocytes.

    abstract::Derivatization of phenothiazine (PTZ, 1) has been a commonly used method to develop drugs with various pharmacological properties. In the present study, a series of PTZ derivatives 1-11 were investigated on the inhibition of the cloned α7 subunit of the human nicotinic acetylcholine receptor (α7-nAChR) expressed in Xe...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/j.phrs.2012.05.008

    authors: Sadek B,Ashoor A,Al Mansouri A,Lorke DE,Nurulain SM,Petroianu G,Wainwright M,Oz M

    更新日期:2012-09-01 00:00:00

  • Insulinotropic action of novel succinic acid esters.

    abstract::The insulinotropic action of several new esters of succinic acid was assessed in isolated rat islets incubated in the presence of 7 mM D-glucose. An efficient secretory response was observed with the monobenzyl, monoisopropyl, monoallyl, monopropyl, monoethyl, monobutyl, dibutyl, dipropyl and diallyl esters of succini...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1006/phrs.1996.0038

    authors: Björkling F,Malaisse-Lagae F,Malaisse WJ

    更新日期:1996-04-01 00:00:00

  • Sulforaphane protects ischemic injury of hearts through antioxidant pathway and mitochondrial K(ATP) channels.

    abstract::Reactive oxygen species are important mediators that exert a toxic effect during ischemia-reperfusion (I/R) injury of various organs. Sulforaphane is known to be an indirect antioxidant that acts by inducing Nrf2-dependent phase 2 enzymes. In this study, we investigated whether sulforaphane protects heart against I/R ...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/j.phrs.2009.11.009

    authors: Piao CS,Gao S,Lee GH,Kim DS,Park BH,Chae SW,Chae HJ,Kim SH

    更新日期:2010-04-01 00:00:00

  • The non-NMDA receptor antagonist NBQX does not affect rats performance in the object recognition task.

    abstract::Though the AMPA receptor has been implicated in several neurodegenerative processes (epilepsy, ischemia, spasticity), its role in cognition is yet to be clarified. The aim of this study was to assess in the rat the effects of the AMPA receptor antagonist NBQX (3.5, 7, 10, 20 and 30 mgkg(-1), i.p.) on learning and memo...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1006/phrs.2001.0898

    authors: Pitsikas N,Rigamonti AE,Cella SG,Muller EE

    更新日期:2002-01-01 00:00:00

  • The effect of ginseng on bile-pancreatic secretion in the rat. Increase in proteins and inhibition of total lipids and cholesterol secretion.

    abstract::Ginseng is one of the most popular herbal remedies. Studies were performed in anaesthetized rats to examine the effect of ginseng on bile secretion. Male Sprague-Dawley rats were anaesthetized with intraperitoneal (i.p.) urethane (1.25 g kg(-1)) and equipped with biliary cannulas inserted into the bile duct through th...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1006/phrs.2002.0961

    authors: Salam OM,Nada SA,Arbid MS

    更新日期:2002-04-01 00:00:00

  • Exogenous insulin-like growth factor (IGF)-1 improves the impaired healing of gastric mucosal lesions in diabetic rats.

    abstract:BACKGROUND:We examined the influence of diabetes mellitus (DM) on the healing of HCl-induced gastric lesions and the healing promoting effect of IGF-1 on these lesions. METHODS:Experiments were performed on rats injected with streptozotocin (STZ, 70 mg kg(-1), i.p.) 5 weeks prior to the experimental session. Diabetic ...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1006/phrs.1999.0581

    authors: Korolkiewicz RP,Tashima K,Fujita A,Kato S,Takeuchi K

    更新日期:2000-02-01 00:00:00

  • Distribution of lipid-soluble antioxidants in lipoproteins from healthy subjects. I. Correlation with plasma antioxidant levels and composition of lipoproteins.

    abstract::The concentration of five lipid-soluble antioxidants (gamma- and alpha-tocopherol, lycopene, beta-carotene and ubiquinol-10) was measured in plasma and very low-density, low-density and high-density lipoproteins (VLDL, LDL and HDL) isolated from young healthy normo- cholesterolemic subjects. Alpha-tocopherol was the e...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1006/phrs.1999.0552

    authors: Perugini C,Bagnati M,Cau C,Bordone R,Zoppis E,Paffoni P,Re R,Albano E,Bellomo G

    更新日期:2000-01-01 00:00:00

  • Endocannabinoids and cardiac contractile function: pathophysiological implications.

    abstract::Endocannabinoids are part of a bioactive lipid signaling system, not only in the central nervous system but also in various peripheral organs. Accumulating evidence implicates dysregulation of the endocannabinoid system (ECS) in the pathogenesis of various cardiovascular diseases, including hypertension, atheroscleros...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审

    doi:10.1016/j.phrs.2009.04.003

    authors: Bátkai S,Pacher P

    更新日期:2009-08-01 00:00:00

  • Transcriptome profiling of NIH3T3 cell lines expressing opsin and the P23H opsin mutant identifies candidate drugs for the treatment of retinitis pigmentosa.

    abstract::Mammalian cells are commonly employed in screening assays to identify active compounds that could potentially affect the progression of different human diseases including retinitis pigmentosa (RP), a class of inherited diseases causing retinal degeneration with compromised vision. Using transcriptome analysis, we comp...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/j.phrs.2016.10.031

    authors: Chen Y,Brooks MJ,Gieser L,Swaroop A,Palczewski K

    更新日期:2017-01-01 00:00:00

  • Effect of praziquantel versus hycanthone on deoxyribonucleic acid content of hepatocytes in murine schistosomiasis mansoni.

    abstract::Cytophotometric measurement of the effect of praziquantel (500 mg/kg for 2 days) versus hycanthone (60 mg/kg for 3 days) on hepatocyte nuclear deoxyribonucleic acid (DNA) content was evaluated in Schistosoma mansoni infected mice. Drugs were given 8 weeks post-infection and repeated weekly for 4 weeks. DNA values of i...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/1043-6618(90)90718-s

    authors: Botros SS

    更新日期:1990-03-01 00:00:00

  • Activity-based protein profiling of the human failing ischemic heart reveals alterations in hydrolase activities involving the endocannabinoid system.

    abstract:AIM:Acute myocardial infarction and subsequent post-infarction heart failure are among the leading causes of mortality worldwide. The endocannabinoid system has emerged as an important modulator of cardiovascular disease, however the role of endocannabinoid metabolic enzymes in heart failure is still elusive. Herein, w...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/j.phrs.2019.104578

    authors: van Esbroeck ACM,Varga ZV,Di X,van Rooden EJ,Tóth VE,Onódi Z,Kuśmierczyk M,Leszek P,Ferdinandy P,Hankemeier T,van der Stelt M,Pacher P

    更新日期:2020-01-01 00:00:00