A Phase I Single-Centre, Randomised, Double-Blind, Placebo-Controlled Study in Healthy Volunteers to Evaluate the Safety, Tolerability, and Pharmacokinetics of Escalating Single Doses and Multiple Doses of SP-8356

This is a 2-part, single-centre, randomised study in healthy males. Part 1 is a double-blind, randomised, placebo-controlled, single ascending dose (SAD) study in healthy males. Part 2 is a double-blind, randomised, placebo-controlled, multiple ascending dose (MAD) study in healthy males.

开始日期2021-01-03

申办/合作机构

Shin Poog Pharmaceutical Co., Ltd.

100 项与 SP-8356 相关的临床结果

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100 项与 SP-8356 相关的转化医学

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100 项与 SP-8356 相关的专利（医药）

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项与 SP-8356 相关的文献（医药）

2024-04-01·International Immunopharmacology

SP-8356 inhibits acute lung injury by suppressing inflammatory cytokine production and immune cell infiltration

Article

作者: Hurh, Sunghoon ; Nguyen, Lan Phuong ; In, Soyeon ; Nguyen, Thai-Uy ; Cho, Minyeong ; Mykhailova, Kateryna ; Kim, Won-Ki ; Ham, Byung-Joo ; Choi, Yongseok ; Kim, Hong-Rae ; Hwang, Jong-Ik

This study investigated the anti-inflammatory and protective properties of SP-8356, a synthetic derivative of (1S)-(-)-verbenone, in a mouse model of LPS-induced acute lung injury (ALI). By targeting intracellular signaling pathways and inflammatory responses, SP-8356 demonstrated a potent ability to attenuate deleterious effects of proinflammatory stimuli. Specifically, SP-8356 effectively inhibited the activation of crucial signaling molecules such as NF-κB and Akt, and subsequently dampened the expression of inflammatory cytokines in various lung cellular components. Intervention with SP-8356 treatment also preserved the structural integrity of the epithelial and endothelial barriers. By reducing immune cell infiltration into inflamed lung tissue, SP-8356 exerted a broad protective effect against ALI. These findings position SP-8356 as a promising therapeutic candidate for pulmonary inflammatory diseases that cause ALI.

2023-08-01·Journal of Extracellular Vesicles

Clathrin light chain A‐enriched small extracellular vesicles remodel microvascular niche to induce hepatocellular carcinoma metastasis

Article

作者: Yao, Yue ; Ng, Tung Him ; Mao, Xiaowen ; Yeung, Cherlie Lot Sum ; Xu, Yi ; Wong, Melody Ym ; Cui, Yunfu ; Lee, Terence Kin Wah ; Yu, Liang ; Yam, Judy Wai Ping ; Gao, Yi ; Zhang, Xiaoxin ; Che, Chi-Ming ; Tey, Sze Keong ; Wong, Samuel Wan Ki

AbstractSmall extracellular vesicles (sEVs) play a key role in exchanging cargoes between cells in tumour microenvironment. This study aimed to elucidate the functions and mechanisms of hepatocellular carcinoma (HCC) derived sEV‐clathrin light chain A (CLTA) in remodelling microvascular niche. CLTA level in the circulating sEVs of HCC patients was analysed by enzyme‐linked immunosorbent assay (ELISA). The functions of sEV‐CLTA in affecting HCC cancerous properties were examined by multiple functional assays. Mass spectrometry was used to identify downstream effectors of sEV‐CLTA in human umbilical vein endothelial cells (HUVECs). Tube formation, sprouting, trans‐endothelial invasion and vascular leakiness assays were performed to determine the functions of sEV‐CLTA and its effector, basigin (BSG) in HUVECs. BSG inhibitor, SP‐8356, was tested in a mouse model of patient‐derived xenografts (PDXs). Circulating sEVs of HCC patients had markedly enhanced CLTA levels than control individuals and were reduced in patients after surgery. HCC derived sEV‐CLTA enhanced HCC cancerous properties, disrupted endothelial integrity and induced angiogenesis. Mechanistically, CLTA remodels microvascular niche by stabilizing and upregulating BSG. Last, SP‐8356 alone or in combination with sorafenib attenuated PDXs growth. The study reveals the role of HCC derived sEV‐CLTA in microvascular niche formation. Inhibition of CLTA and its mediated pathway may illuminate a new therapeutic strategy for HCC patients.

2023-05-28·Cell journal

SP-8356 (A Verbenone Derivative) Inhibits Proliferation, Suppresses Cell Migration and Invasion and Decreases Tumor Growth of Osteosarcoma: Role of PGC-1α/TFAM and AMPK-Activation.

Article

作者: Yu, Hong ; Chen, Xiaoyan ; Cui, Wenning ; Yang, Dengfeng

OBJECTIVEOsteosarcoma (OS) is an uncommon sarcoma with osteoid formation in conjunction with malignant mesenchymal cells on histological examination. SP-8356 has been reported to exhibit anti-cancer properties in human cancers. However the impact of SP-8356 on OS is largely unknown. The metabolic pathways are coordinated by AMPactivated protein kinase (AMPK), which maintains a balance between the supply and demand of nutrients and energy. This study aimed to investigate effect of SP-8356 on proliferation and apoptosis of OS cells and tumor growth in mice. Furthermore, involvement of PGC-1α/TFAM and AMPK-activation was studied.MATERIALS AND METHODSIn the experimental study, Saos-2 and MG63 cells were cultured with SP-8356 for 24 hours and analysed for cellular proliferation using MTT assay. DNA fragmentation was studied using ELISA based kit. Furthermore, transwell chambers assay was used to determine cell migration and cell invasion. Targeted protein expression levels were assessed using western blotting. For in vivo studies, mice (5-6 weeks old) were implanted with either Saos-2 or MG63 cells on dorsal surface subcutaneously and they were administered with SP-8356 (10 mg/kg) for two weeks prior to bone tumor induction.RESULTSWe found that SP-8356 exerted anti-proliferative effects on Saos-2 and MG63 cells. Furthermore, SP-8356 treatment significantly restricted migration and invasion of Saos-2 and MG63 cells. Compared to the control, SP-8356 significantly reduced apoptotic cell death, while it increased PGC-1α and TFAM expressions. Without affecting body weight, SP-8356 significantly reduced tumor development in mice, as compared to the control group.CONCLUSIONSP-8356 was found to inhibit proliferation, suppressed cells migration and invasion and decreased OS tumor growth. Furthermore, SP-8356 was found to act through PGC-1α/TFAM and AMPK activations. SP-8356 can be therefore used as therapeutic agent for OS treatment.

100 项与 SP-8356 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
动脉粥样硬化	临床前	英国	Shin Poog Pharmaceutical Co., Ltd.	2021-01-03
缺血性卒中	临床前	英国	Shin Poog Pharmaceutical Co., Ltd.	2021-01-03
动脉硬化	临床前	韩国	Shin Poog Pharmaceutical Co., Ltd.	-