SMS synthase x SGMS2

Last update 08 May 2025

Basic Info

Related Targets

SMS synthaseSGMS2

Drugs associated with SMS synthase x SGMS2

CN119320385

Patent Mining

Target

SGMS2 x SMS synthase

Mechanism

SGMS2 inhibitors

Active Org.

Fudan University

Originator Org.

Fudan University

Active Indication

Alzheimer Disease [+6]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with SMS synthase x SGMS2

100 Translational Medicine associated with SMS synthase x SGMS2

0 Patents (Medical) associated with SMS synthase x SGMS2

188

Literatures (Medical) associated with SMS synthase x SGMS2

01 Mar 2025·The FEBS Journal

Hypoxia‐induced increase in sphingomyelin synthase 2 aggravates ischemic skeletal muscle inflammation

Article

Author: Yasui, Hironobu ; Murakami, Hironobu ; Fukuyama, Tomoki ; Yamashita, Tadashi ; Naya, Yuko ; Aihara, Naoyuki ; Kamiie, Junichi ; Mizugaki, Hinano ; Nagane, Masaki ; Sato‐Akaba, Hideo ; Inanami, Osamu ; Kuppusamy, Periannan ; Kmiec, Maciej ; Yasuda, Ibuki ; Mizunoya, Wataru

Critical limb ischemia (CLI) is the most advanced stage of peripheral arterial disease, posing a high risk of mortality. Sphingomyelin, a sphingolipid synthesized by sphingomyelin synthases (SMSs) 1 and 2, plays an essential role in signal transduction as a component of lipid rafts. However, the role of sphingomyelin in the inflammation of ischemic skeletal muscles remains unclear. In this study, we analyzed the roles of sphingomyelin and SMSs in CLI‐induced myopathy using a mouse hindlimb ischemia model. We observed that hypoxia after CLI triggered an increase in SMS2 levels, thereby elevating sphingomyelin concentrations in ischemic skeletal muscles. The expression of SMS2 and sphingomyelin was induced by hypoxia in C2C12 myotubes and regulated by the prolyl hydroxylase domain enzyme. Additionally, SMS2 deficiency suppressed skeletal muscle inflammation after CLI, attenuated the phosphorylation of inhibitor of κBα (IκBα), and reduced the nuclear translocation of nuclear factor κB (NFκB) p65. Meanwhile, the administration of sphingomyelin hampered skeletal muscle inflammation by inhibiting IκBα phosphorylation and NFκB p65 nuclear translocation and extending inflammation post‐CLI. Our results suggest that hypoxia‐induced enhancement in SMS2 levels and the consequent increase in sphingomyelin expression levels promote inflammation in ischemic muscle tissues via the NFκB pathway and propose sphingomyelin as a potential therapeutic target in patients with CLI and other hypoxia‐related inflammatory diseases.

01 Mar 2025·Bone Reports

A novel SGMS2 mutation associated with high bone mass; description of an affected family with recurrent fragility fractures

Article

Author: Prajapti, Ashka ; Pande, Minal ; Vyas, Parin ; Katam, Kishore K ; Kotecha, Udhaya ; Kedar, Ketki ; Patra, Shinjan ; Jena, Sweekruti

SGMS2 mutation can present with childhood-onset low bone mass and recurrent fragility fractures. We report a 25-year-old man with a three-generation family history of recurrent fragility fractures and diffuse high bone mass. He was found to have a heterozygous frameshift variant c.1052_1074dup in the SGMS2 gene. Our case highlights a novel genetic mutation in the SGMS2 gene and reports the first family of SGMS2 mutation with high bone mass.

01 Mar 2025·Gastroenterology

Stromal Stiffness-Regulated IGF2BP2 in Pancreatic Cancer Drives Immune Evasion via Sphingomyelin Metabolism

Article

Author: Zhou, Cong ; Zhang, Zifeng ; Chen, Chen ; Tan, Zhen ; Rong, Zeyin ; He, Qing ; Liu, Xiaomeng ; Wang, Wei ; Liu, Yuan ; Liao, Yingna ; Chen, Yueyue ; Li, Yangyi ; Shi, Si ; Xu, Jin ; Lei, Yubin ; Lu, Siyuan ; Tang, Rong ; Yu, Xianjun ; Du, Qiong ; Zhang, Chaoyi ; Wu, Zijian ; Xiao, Mingming ; Li, Pengcheng

BACKGROUND AND AIMSImmunotherapy has shown promising results in cancer treatment; however, it remains largely ineffective for pancreatic ductal adenocarcinoma (PDAC). N6-methyladenosine (m6A), known for its crucial role in cancer biology, is not yet fully understood regarding immune evasion. This study aims to elucidate the associations and mechanisms linking m6A modification with immune evasion in PDAC and propose strategies for clinical intervention.METHODSA multimodal PDAC cohort of 122 patients was developed, integrating transcriptomic profiling, imaging mass cytometry, and m6A quantification to identify m6A regulators associated with immunosuppressive tumor microenvironment (TME) and clinical outcomes. Findings were validated across 6 independent PDAC cohorts. Assays including MeRIP, RIP, and RNA pull-down confirmed that IGF2BP2 binds to targets, whereas scRNA-seq, flow cytometry, and mIHC profiled the TME. Preclinical interventions were tested in PDAC organoids, patient-derived tissue fragments, and humanized mouse models.RESULTSOur comprehensive analysis identified the m6A reader protein IGF2BP2 as a critical factor associated with poor prognosis in PDAC, linked to reduced effector cell infiltration and a fibrotic TME. High matrix stiffness in PDAC stabilized IGF2BP2, which subsequently promoted sphingomyelin synthesis via SGMS2 up-regulation. This pathway facilitates PD-L1 localization on membrane lipid rafts, enhancing immune evasion. The elastographic properties of PDAC enabled noninvasive screening of patients with overexpressed IGF2BP2/SGMS2. Disrupting sphingomyelin synthesis improved antitumor immunity and suppressed PDAC growth in humanized mice, highlighting immunotherapeutic opportunities for PDAC.CONCLUSIONSThese findings emphasize the critical interplay between extrinsic matrix stiffness and intrinsic IGF2BP2-regulated sphingomyelin synthesis, identifying a promising target for immunotherapeutic strategies in PDAC.

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