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 Resjournal_title
Pharmacological researchauthors
Chew WS,Wang W,Herr DRdoi
10.1016/j.phrs.2016.09.025subject
Has Abstractpub_date
2016-11-01 00:00:00pages
521-532issue
Pt Aeissn
1043-6618issn
1096-1186pii
S1043-6618(16)30877-5journal_volume
113pub_type
杂志文章,评审abstract：:Short-chain fatty acids (SCFAs), mainly including acetate, propionate, and butyrate, are metabolites produced during the bacterial fermentation of dietary fiber in the intestinal tract. They are believed to be essential factors affecting host health. Most in vitro and ex vivo studies have shown that SCFAs affect the r...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2021.105420
更新日期：2021-01-09 00:00:00
abstract：:Sesquiterpene lactones (SL) are natural bioactive molecules indicated as potential scaffolds for anti-inflammatory and analgesic drug design. However, their anti-inflammatory applicability remains underestimated since the impact of SL on inflammatory nociception and tissue repair are overlooked. Thus, we used an integ...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2020.105303
更新日期：2020-11-16 00:00:00
abstract：:Some bladder disorders, such as obstructive bladder and hyperactivity, may be caused partly by ischemia/reperfusion injury (I/R). The neuroprotective effects of estrogens were demonstrated in in vitro studies and a great interest in soy isoflavones (genistein and daidzein) as alternative to the synthetic estrogen rece...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2012.06.007
更新日期：2012-10-01 00:00:00
abstract：:To assess the potential role of vasoactive cardiac eicosanoids in the modulation of coronary flow, we measure thromboxane(TX)B2, 6-keto-prostaglandin(PG)F1 alpha, PGE2 and sulphido-peptide leukotrienes (LTC4, D4, E4) in the coronary effluent of isolated perfused rat heart in both baseline and post-ischaemic conditions...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/1043-6618(92)90233-2
更新日期：1992-12-01 00:00:00
abstract：:Cells continuously turn over proteins through cycles of synthesis and degradation in order to maintain a functional proteome and to exert a tight control in the levels of regulatory proteins. Selective degradation of proteins was initially thought to be an exclusive function of the ubiquitin-proteasome system, however...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2012.10.002
更新日期：2012-12-01 00:00:00
abstract：:In China, child and adolescent pediatricians often face challenges in treating children with the appropriate medications. Within the last 8 years, the Chinese government has already initiated a series of policies to promote development of age-appropriate medicines for children. In this study,we introduced the current ...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2019.104412
更新日期：2019-10-01 00:00:00
abstract：:Epidemiological studies have implied that diabetes mellitus (DM) will become an epidemic accompany with metabolic and endocrine disorders worldwide. Most of DM patients are affected by type 2 diabetes mellitus (T2DM) with insulin resistance and insulin secretion defect. Generally, the strategies to treat T2DM are diet...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2018.01.015
更新日期：2018-04-01 00:00:00
abstract：:The understanding of signaling cascades involved in the induction, promotion, and progression of cancer, although advanced in recent years, is still incomplete. Tracing the imbalance of the impaired, physiologically-essential cellular signaling that drives the neoplastic process is a complex issue. This review discuss...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2012.03.014
更新日期：2012-07-01 00:00:00
abstract：:Inflammatory reaction and cell apoptosis are two important processes in intestinal ischemia/reperfusion (II/R) injury, and exploration of effective lead compounds against II/R injury via regulating inflammation and apoptosis is critical important. In this paper, the results indicated that dioscin significantly increas...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2018.11.040
更新日期：2019-01-01 00:00:00
abstract：:Severely obese patients undergoing bariatric surgery (BS) are at increased risk for venous thromboembolism (VTE). How standard low molecular weight heparin (LMWH) regimen should be adapted to provide both sufficient efficacy and safety in this setting is unclear. We aimed to compare the influence of four body size des...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2018.02.012
更新日期：2018-05-01 00:00:00
abstract：:Cytochrome P450-dependent arachidonic acid (AA) metabolism by medullary thick ascending limb of the loop of Henle (mTALH) cells, corneal epithelium and other transporting epithelia, such as those of the intestines, generate metabolites which affect Na(+)-K(+)-ATPase activity, vasomotion and, thereby, organ function. F...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/1043-6618(91)90046-z
更新日期：1991-05-01 00:00:00
abstract：:Familial hypercholesterolemia (FH) is a genetic autosomal dominant disorder caused by an impaired receptor-mediated low-density lipoprotein (LDL) removal from the circulation, mainly due to disruptive autosomal co-dominant mutations in the LDL receptor (LDLr) gene, but also less frequently in the apolipoprotein B100 (...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2019.03.016
更新日期：2019-05-01 00:00:00
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
更新日期：1996-02-01 00:00:00
abstract：:Kidney injury is one of the main complications of obstructive jaundice (OJ) and its pathogenesis has not been clarified. As an independent risk factor for OJ associated with significant morbidity and mortality, it can be mainly divided into two types of morphological injury and functional injury. We called these dysfu...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2020.105311
更新日期：2021-01-01 00:00:00
abstract：:The available studies have reported the benefits of statins on all-cause and cardiovascular mortality in chronic kidney disease (CKD) patients. However studies in end-stage renal disease patients on dialysis yielded conflicting results. Therefore, we performed a meta-analysis and provide the most reliable trial data t...
journal_title：Pharmacological research
pub_type： 杂志文章,meta分析
doi：10.1016/j.phrs.2013.03.007
更新日期：2013-06-01 00:00:00
abstract：:Treatment of MC3T3E-1 osteoblast cultures with combined interferon- gamma(IFN- gamma), lipopolysaccharide (LPS) and tumor necrosis factor- alpha(TNF- alpha) induces expressions of inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6), resulting in sustained releases of large amounts of nitric oxide and IL-6....
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.2000.0778
更新日期：2001-03-01 00:00:00
abstract：:Biotechnologicals are an invaluable resource in the treatment of patients with inflammatory rheumatic diseases (IRD) non-responsive or intolerant to conventional therapies. However, they are the main driver for increase in direct costs and represent a significant economic burden to healthcare systems worldwide. Since ...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2019.104467
更新日期：2019-11-01 00:00:00
abstract：:Flibanserin has been reported to be an agonist at 5-HT1A-receptors and an antagonist at 5-HT2A receptors, with higher affinity for 5-HT1A receptors. Despite the fact that less receptor occupation is required by full agonists than by antagonists to exert their effects, flibanserin was shown to exert 5-HT2A antagonism a...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.2000.0762
更新日期：2001-02-01 00:00:00
abstract：:A bovine dopamine transporter (bDAT) cDNA was transfected into CV-1 cells, a cell line that lacks vesicular storage and release mechanisms. Using this cell line, the effects of neuroleptic drugs on DAT-mediated uptake and release of dopamine (DA) were examined. All of the neuroleptic drugs tested, inhibited DA uptakes...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：
更新日期：1997-05-01 00:00:00
abstract：:Pulsatilla Decoction (Bai-Tou-Weng-Tang) has been used medically in China for thousands of years for the treatment of diseases caused by bacteria. In recent decades, Pulsatilla Decoction is becoming a well-known formula prescription used for the treatment of ulcerative colitis in traditional Chinese medicine. Pulsatil...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2020.105079
更新日期：2020-10-01 00:00:00
abstract：:Treatment of pediatric diabetes can be challenging. Strict glucose control can be accompanied by hypoglycemia and weight gain. Recently, there have been many developments in insulin preparations and delivery methods which make insulin levels more close to a physiologic pattern. Newly developed rapid/long acting analog...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2011.08.011
更新日期：2012-01-01 00:00:00
abstract：:Hydrogen sulfide (H2S) is an endogenously produced signaling molecule synthesized by cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST). Given that H2S exerts significant effects on bioenergetics and metabolism, the goal of the current study was to determine th...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2017.09.023
更新日期：2018-02-01 00:00:00
abstract：:Regulatory T cells (Tregs) modulate ongoing immune responses to prevent autoimmunity in healthy bodies and inhibit effective anti-tumor immunity responses in tumor patients, leading to tumor progression. The function of Tregs in tumor immunity suggests that elimination of Tregs in the host may enhance the anti-tumor i...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2020.104659
更新日期：2020-03-01 00:00:00
abstract：:This paper describes a new sensitive gas chromatographic method with electron capture detector to assay estazolam in human plasma, which has been developed and validated for pharmacokinetic purposes. The drug and the internal standard (triazolam) were extracted from plasma buffered at pH 9.0 into toluene and analysed ...
journal_title：Pharmacological research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1006/phrs.1997.0144
更新日期：1997-04-01 00:00:00
abstract：:In the isolated myometrium obtained from pregnant women, diphenylhydantoin inhibited both spontaneous and K(+)-evoked contractions within the same range of potency. Nicardipine was less effective in inhibiting spontaneous than K(+)-induced contractions, whereas trifluoperazine was only effective against spontaneous co...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(05)80051-9
更新日期：1990-09-01 00:00:00
abstract：:Psoriasis is one of the most common skin disorders characterized by erythematous plaques that result from hyperproliferative keratinocytes and infiltration of inflammatory leukocytes into dermis and epidermis. Recent studies suggest that IL-23/IL-17A/IL-22 cytokine axis plays an important role in the pathogenesis of p...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2015.06.001
更新日期：2015-09-01 00:00:00
abstract：:Baroreflex plays a crucial role in regulation of arterial blood pressure (BP). Recently, Piezo1 and Piezo2, the mechanically-activated (MA) ion channels, have been identified as baroreceptors. However, the underlying molecular mechanism for regulating these baroreceptors in hypertension remains unknown. In this study,...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2020.105391
更新日期：2020-12-19 00:00:00
abstract：:Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide that afflicts human health. With the in-depth study of the disease, its pathogenesis has gradually become clear. Although great breakthroughs have been made in the research of ALD, the research and development of drugs related to ALD has...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2019.104501
更新日期：2019-12-01 00:00:00
abstract：:Vascular responses to hypoxia are heterogeneous and involve the release of vasodilators substances such as nitric oxide (NO) and prostacyclin (PGI(2)). In vitro studies have shown that Vitamin K(1) modulates the release of arachidonic acid (AA) in vascular cells, and thus inhibits the capacity of blood vessels to synt...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s104366180200227x
更新日期：2002-12-01 00:00:00
abstract：:The rationale underlying therapeutic strategies designed to inhibit the action of endogenous sex hormones in malignant breast cells is provided by the demonstration of their involvement in supporting the development and growth of breast carcinoma. The surgical removal of steroid-secreting glands, in order to reduce th...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1006/phrs.1998.0437
更新日期：1999-05-01 00:00:00
