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Last update 23 Jan 2025

SGPL1

Last update 23 Jan 2025

Basic Info

Synonyms

hSPL, KIAA1252, S1PL

+ [6]

Introduction

Cleaves phosphorylated sphingoid bases (PSBs), such as sphingosine-1-phosphate, into fatty aldehydes and phosphoethanolamine. Elevates stress-induced ceramide production and apoptosis (PubMed:11018465, PubMed:14570870, PubMed:24809814, PubMed:28165339). Required for global lipid homeostasis in liver and cholesterol homeostasis in fibroblasts. Involved in the regulation of pro-inflammatory response and neutrophil trafficking. Modulates neuronal autophagy via phosphoethanolamine production which regulates accumulation of aggregate-prone proteins such as APP (By similarity). Seems to play a role in establishing neuronal contact sites and axonal maintenance (By similarity).

Drugs associated with SGPL1

LX-2931

Target

SGPL1

Mechanism

SGPL1 inhibitors

Active Org.

AC BioScience SAStartup

Originator Org.

Lexicon Pharmaceuticals, Inc.

Active Indication

Pancreatic Cancer [+2]

Inactive Indication

Darier Disease [+2]

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

LX-2932

Target

SGPL1 x Sphingosine 1-phosphate lyase

Mechanism

SGPL1 inhibitors [+1]

Active Org.

Lexicon Pharmaceuticals, Inc.

Originator Org.

Lexicon Pharmaceuticals, Inc.

Active Indication

Rheumatoid Arthritis

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

CN116531406

Patent Mining

Target

SGPL1

Mechanism-

Active Org.

Tian Qing Stem Cell Co., Ltd.

Originator Org.

Tian Qing Stem Cell Co., Ltd.

Active Indication

Endocrinology and Metabolic Disease

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with SGPL1

EUCTR2018-000373-80-FR

/ Not yet recruitingPhase 1/2

A Phase 1/2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Arm Study of the Safety and Efficacy of LX3305, a Sphingosine-1-Phosphate Lyase Inhibitor, for Treatment of Darier’s Disease or Hailey-Hailey Disease - DERM-101

Start Date24 May 2018

Sponsor / Collaborator

Dermecular Therapeutics, Inc.

NCT01417052

/ CompletedPhase 1

A Phase 1, Single-Center, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study to Determine the Safety and Efficacy of Daily Orally Administered LX3305 in Subjects With Active Rheumatoid Arthritis (RA)

The primary objective of this study is to determine the safety of LX3305 in a dose escalation compared with placebo over 12 weeks in subjects with active rheumatoid arthritis (RA).

Start Date01 Sep 2011

Sponsor / Collaborator

Lexicon Pharmaceuticals, Inc.

EUCTR2009-012705-19-BG

/ Not yet recruitingNot Applicable

A Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled, Multiple-dose Study to Determine the Safety and Efficacy of Daily Orally Administered LX3305 in Subjects with Active Rheumatoid Arthritis (RA) on Stable Methotrexate (MTX) Therapy - LX3305.201

Start Date29 Sep 2009

Sponsor / Collaborator

Lexicon Pharmaceuticals, Inc.

100 Clinical Results associated with SGPL1

100 Translational Medicine associated with SGPL1

0 Patents (Medical) associated with SGPL1

1,432

Literatures (Medical) associated with SGPL1

01 Mar 2025·International Journal of Biological Macromolecules

Study of the SPL gene family and miR156-SPL module in Populus tomentosa: Potential roles in juvenile-to-adult phase transition and reproductive phase

Article

Author: Li, Ying ; Deng, Yufei ; Qin, Debin ; An, Xinmin

Populus tomentosa, a deciduous tree species distinguished by its significant economic and ecological value, enjoys a wide-ranging natural distribution. However, its long juvenile period severely restricts the advancement of breeding work. The SPL gene family, a distinctive class of transcription factors exclusive to the plant kingdom, is critical in various processes of plant growth and development. The miR156-SPL molecular module stands as an indispensable regulatory mechanism in the transition from the vegetative juvenile phase to the adult phase in plants. Consequently, this research endeavored a methodical and exhaustive exploration of the SPL gene family within the P.tomentosa species, synergistically integrating the miR156 family into the analysis. A total of 56 PtSPL genes were identified and subjected to a comprehensive analysis of their gene structure, conserved motifs, collinearity relationships, chromosomal localization, and promoter cis-acting elements. Further analysis of gene expression profiles confirmed the pivotal role of PtSPLs in the reproductive phase and tissue development of P. tomentosa. In addition, 11 members of miR156 in P. tomentosa were identified and their sequences analyzed, elucidating the miR156-SPL regulatory network. The target relationship between miR156k and PtSPLs was further validated by detecting the expression levels of PtSPLs in transgenic poplars overexpressing 35S::MIR156k. This comprehensive study lays a robust theoretical foundation for the continued exploration and application of the SPL genes in P. tomentosa, opening avenues for future research and potential advancements in plant biology and breeding strategies.

01 Feb 2025·Journal of Ethnopharmacology

Efficacy of spilanthol and Acmella oleracea (L.) R. K. Jansen (Asteraceae) extract against Schistosoma mansoni infection

Article

Author: Souza, Lara Cruz de ; Da Silva Filho, Ademar A ; Souza Costa, Danilo de ; Carvalho, Lara S Aleixo de ; Cajas, Rayssa A ; Cajas, Rayssa A. ; Moraes, Josué de ; Carvalho, Lara S. Aleixo de ; Leal, Carla Monteiro ; Filho, Ademar A. da Silva ; Fukui-Silva, Lucas

ETHNOPHARMACOLOGICAL RELEVANCEAcmella oleracea (L.) R. K. Jansen, commonly referred to as "Jambu", is a valuable medicinal plant native to the Amazon regions. Inflorescences of A. oleracea is utilized as local anesthetic properties and for its insecticidal, antiparasitic, and anthelmintic attributes.AIMS OF THIS STUDYThis study aimed to evaluate the in vitro and in vivo antiparasitic properties of A. oleracea extract and spilanthol (SPL) against Schistosoma mansoni.MATERIALS AND METHODSThe ethanolic extract of A. oleracea inflorescences (AoE) was prepared, analyzed by HPLC-DAD, and characterized by UHPLC-HRMS/MS. SPL was isolated from AoE by chromatographic fractionation. The antischistosomal properties of AoE and SPL were evaluated in vitro against adult schistosomes and in preclinical assays using murine models of patent S. mansoni infection.RESULTSThrough UHPLC-HRMS/MS analysis, 14 alkamides were annotated in AoE. HPLC-DAD analysis of AoE revealed a peak with a substantial relative area of ∼85%, which was isolated and identified as SPL. AoE and SPL caused mortality of adult schistosomes ex vivo, showing EC₅₀ values of 32.6 μg/mL and 27.8 μM, respectively, without affected Vero cells or Caenorhabditis elegans. In preclinical studies, the oral administration (400 mg/kg) of AoE and SPL resulted in significant reductions in worm burden of 28% and ∼42%, respectively. Additionally, SPL exhibits remarkable effects on oogram, decreasing egg burden and the number of immature eggs by over 80%, while also promoting significant reductions in hepato- and splenomegaly.CONCLUSIONSThe research underscores the antischistosomal activity of A. oleracea highlighting the potential of SPL as a lead for the development of new schistosomicidal drugs and encouraging further studies to validate the traditional anthelmintic use of A. oleracea inflorescences.

01 Feb 2025·NeuroImage

Continuous theta-burst stimulation demonstrates language-network-specific causal effects on syntactic processing

Article

Author: Gao, Chenyang ; Yang, Mingchuan ; Wu, Junjie ; Qu, Xingfang ; Ke, Yuming ; Chen, Luyao ; Hartwigsen, Gesa ; Cheng, Yao

Hierarchical syntactic structure processing is proposed to be at the core of the human language faculty. Syntactic processing is supported by the left fronto-temporal language network, including a core area in the inferior frontal gyrus as well as its interaction with the posterior temporal lobe (i.e., "IFG + pTL"). Moreover, during complex syntactic processes, left IFG also interacts with executive control regions, such as the superior parietal lobule (SPL). However, the functional relevance of these network interactions is largely unclear. In particular, it remains to be demonstrated whether the language network plays a specific causal role in comparatively challenging syntactic processes, separable from the interaction between IFG and other general cognitive regions (i.e., "IFG + SPL" in the present study). The present study was designed to address this question. Thirty healthy adult Chinese native speakers underwent four continuous theta-burst stimulation (cTBS) sessions: stimulation over IFG, stimulation over IFG + pTL, stimulation over IFG + SPL, and sham stimulation over IFG + irrelevant region in a pseudo-randomized order. In each session, participants were required to label the syntactic categories of jabberwocky sequences retaining real Chinese function words (e.g., "ムウ" is labeled as a verb phrase (VP): "[_VP [V]N]", similar to "ziff-ed a wug", where "ziff" and "wug" are nonsense pseudowords, and the whole phrase is a VP). Contrasted with sham cTBS, change percentage of accuracy rates (ΔACCR%), reaction times (ΔRT%), and coefficient of variation (ΔCV%) were calculated and compared across conditions. First-order behavioral results showed a significantly higher ΔCV% after stimulating IFG + pTL compared to stimulating the IFG + SPL, indicating that syntactic processing became more unstable. Second-order representational similarity analysis (RSA) results revealed that cTBS effects on IFG + pTL selectively depended on the hierarchical embedding depth, a key measure of syntactic hierarchical complexity, whereas the effects on IFG + SPL were sensitive to the dependency length, a crucial index reflecting the working memory load. Collectively, these findings reveal the specific causal relevance of the language areas for hierarchical syntactic processing, separable from other general cognitive (such as working memory) capacities. These results shed light on the uniqueness and the specific causal role of the language network for the human language faculty, further supporting the causally separable view of the functional dissociation between the language network and the domain-general/multiple-demand network.

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SGPL1

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