索西替尼(Solcitinib) - 药物靶点：JAK1_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [4]

靶点

JAK1

作用机制

JAK1抑制剂(酪氨酸蛋白激酶JAK1抑制剂)

治疗领域

免疫系统疾病皮肤和肌肉骨骼疾病消化系统疾病

在研适应症-

非在研适应症

溃疡性结肠炎斑块状银屑病银屑病+ [1]

原研机构

GSK Plc

在研机构-

非在研机构

GSK PlcGlaxoSmithKline Intellectual Property (No. 2) Ltd.GlaxoSmithKline Research & Development Ltd.

+ [2]

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)终止

特殊审评特殊审批 (中国)

结构

分子式C22H23N5O2

InChIKeyMPYACSQFXVMWNO-UHFFFAOYSA-N

CAS号1206163-45-2

关联

17

项与索西替尼相关的临床试验

NL-OMON38611 / CompletedN/A

An open label, experimental medicine investigation of the safety and tolerability of 400 mg b.i.d. GSK2586184 in patients with moderate to severely active ulcerative colitis (200208) - 200208 (JAK)

开始日期2014-01-09

申办/合作机构

GlaxoSmithkline BV

NCT02000453 / Terminated临床1期

An Open Label, Experimental Medicine Investigation of the Safety and Tolerability of 400 mg b.i.d. GSK2586184 in Patients With Moderate to Severely Active Ulcerative Colitis.

This is an open label exploratory study to investigate the safety of 400 milligram (mg ) twice a day (b.i.d.) GSK2586184 in patients with moderate to severe, active ulcerative colitis (UC). Study medication will be administered orally (as tablets), twice daily, for up to 8 weeks (56 days). Study medication will be taken with food. Each subject will have 6 out-patient visits: Screening (Day -30 to -1); Baseline and Start of treatment (Day 1); Week 2 (Day 14); Week 4 (Day 28); Week 8 (Day 56); and Follow-up (Week 12; Day 84). Visit windows for weeks 2, 4 and 8 will be + 2 days. The primary objective of this study is to assess the safety and tolerability of GSK2586184. The primary endpoints to measure safety are laboratory tests (including haematology, clinical chemistry and serum creatinine), vital signs, 12-lead electrocardiogram (ECG), physical examination, and adverse event reporting. These are standard measurements to evaluate safety.

开始日期2013-12-20

申办/合作机构

GSK Plc

NCT01953835 / Completed临床1期

A Two-part Healthy Volunteer Study to Investigate Both the Interaction of GSK2586184 With Rosuvastatin and Simvastatin and to Compare the Pharmacokinetics of Two Different Formulations of GSK2586184

This study is a Phase I, two-part, open-label study designed to evaluate the effect of repeated doses of GSK2586184 on the pharmacokinetics (PK) of Simvastatin and Rosuvastatin in healthy volunteers (Cohort A), and to evaluate the pharmacokinetics of a new tablet formulation of GSK2586184 in healthy male volunteers (Cohort B). Cohort A is a single sequence drug interaction study in which 28 subjects (14 female and 14 male subjects) will be enrolled. Each subject will receive single doses of Simvastatin and Rosuvastatin on two occasions, once alone and once following administration of repeated doses of GSK2586184. Cohort B is a 3-way crossover PK study in which 9 male subjects will be randomized (3 subjects to each treatment sequence). Each subject will receive a single dose of the standard formulation of GSK2586184 with food and two doses of a new formulation of GSK2586184, once with food and once in a fasted state, according to their treatment sequence, with a 3-day wash out between doses. The primary aim of the study is to investigate the effects of GSK2586184 on the pharmacokinetics of the 2 statins and to assess the impact of dosing with and without food on a new formulation of GSK2586184 tablet.

开始日期2013-10-04

申办/合作机构

GSK Plc

100 项与索西替尼相关的临床结果

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100 项与索西替尼相关的转化医学

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100 项与索西替尼相关的专利（医药）

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10

项与索西替尼相关的文献（医药）

2022-12-31·Pharmaceutical Biology

Pseudolycorine chloride ameliorates Th17 cell-mediated central nervous system autoimmunity by restraining myeloid-derived suppressor cell expansion

Article

作者: Li, Juan ; Zhu, Xinying ; Zhang, Gan ; Li, Limei ; Wang, Yantang ; Yang, Fan ; Mo, Chunfen ; Leng, Xiao

CONTEXTThe alkaloids of Narcissus tazetta L. var. Chinensis Roem (Amaryllidaceae) have antitumor and antiviral activities. However, the immunopharmacological effects of one of its constituents, pseudolycorine chloride (PLY), have not been reported yet.OBJECTIVEWe evaluated the effect of PLY on myeloid-derived suppressor cells (MDSCs) expansion and differentiation into monocyte-like MDSCs (M-MDSCs) and examined whether PLY alleviates Th17 cell-mediated experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS).MATERIALS AND METHODSIn vitro, MDSCs were treated with PLY (0.67, 2 and 6 μM) or solcitinib (10 μM, positive control) for 48 or 96 h, and their proliferation, expansion, and differentiation into M-MDSCs were examined by flow cytometry. Myelin oligodendrocyte glycoprotein (MOG_35-55) was used to induce EAE in female C57BL/6 mice, and the mice were treated with 40 mg/kg/d PLY or 1 mg/kg/d FK-506 (tacrolimus, positive control) for 21 days. Inflammatory infiltration, spinal cord demyelination, and MDSCs and Th17 cells infiltration into the spinal cord were examined using haematoxylin and eosin staining, Luxol fast blue staining, and immunofluorescence, respectively.RESULTSIn vitro, PLY (IC50/24 h = 6.18 μM) significantly inhibited IL-6 and GM-CSF-induced MDSCs proliferation, expansion and differentiation into M-MDSCs at all concentrations used. However, these concentrations did not show cytotoxicity. In mice, PLY (40 mg/kg) treatment alleviated EAE and inhibited inflammatory infiltration, demyelination, and MDSCs and Th17 cells infiltration into the spinal cord.DISCUSSION AND CONCLUSIONSPLY may be an excellent candidate for the treatment of MS and other autoimmune diseases.

2022-11-01·Journal of the European Academy of Dermatology and Venereology

The efficacy and safety of tofacitinib, peficitinib, solcitinib, baricitinib, abrocitinib and deucravacitinib in plaque psoriasis – A network meta‐analysis

Review

作者: Jiang, X. ; Guo, L. ; Zhang, L. ; Wang, L.

AbstractJanus kinase (JAK) inhibitors are novel treatment approaches for psoriasis. However, there is no direct comparison of JAK inhibitors in plaque psoriasis. In order to compare the efficacy and safety of JAK inhibitors in psoriasis, we conducted a network meta‐analysis using eligible randomized clinical trials (RCTs). The efficacy of JAK inhibitors was evaluated using a 75% improvement in Psoriasis Area and Severity Index (PASI75) from baseline, and the proportion of patients achieving the Physician’s Global Assessment (PGA) response. The incidence of treatment‐related adverse events (AEs) was also assessed. A total of eight RCTs with tofacitinib, peficitinib, solcitinib, baricitinib, abrocitinib and deucravacitinib were included. A total of 3612 participants who were diagnosed with moderate‐to‐severe plaque psoriasis were analysed. Overall, JAK inhibitors showed superior PASI75 response over placebo at both 8 and 12 weeks. Among all included JAK inhibitors, tofacitinib 15 mg twice a day (BID) had the highest probability of achieving PASI75 at both 8 and 12 weeks (SUCRA = 0.938 and 0.937, separately), followed by tofacitinib 10 mg BID (SUCRA = 0.905 and 0.908, separately) and deucravacitinib 12 mg once daily (QD) (SUCRA = 0.874 and 0.837, separately). A similar finding was observed for PGA response. Safety assessment showed that all JAK inhibitors had non‐inferior safety compared with placebo, except for deucravacitinib 6 mg BID and 12 mg QD. Tofacitinib 2 mg BID was the first‐ranked drug for safety profile followed by deucravacitinib 3 mg QD, and tofacitinib 5 mg BID. When comprehensively evaluated the efficacy and safety, tofacitinib (2 mg, 5 mg, 10 mg, 15 mg BID) was superior to other included JAK inhibitors with satisfying PASI75 and PGA response, as well as relatively low incidence of AEs. Our study confirmed that JAK inhibitors had promising treatment efficacy for moderate‐to‐severe plaque psoriasis. Tofacitinib showed superior efficacy and safety over peficitinib, solcitinib, baricitinib, abrocitinib and deucravacitinib.

2020-12-01·Clinical Reviews in Allergy & Immunology2区 · 医学

JAK Inhibitors: Prospects in Connective Tissue Diseases

2区 · 医学

Review

作者: Zhao, Jiuliang ; Li, Jing ; You, Hanxiao ; Zeng, Xiaofeng ; Li, Mengtao ; Wang, Qian ; Tian, Xinping ; Xu, Dong

The dysregulation of the JAK-STAT pathway is associated with various immune disorders. Four JAK inhibitors have been approved for rheumatoid arthritis (RA), and numerous JAK inhibitors are currently being tested in phase II and III trials for the treatment of various autoimmune inflammatory diseases. In this narrative review, we elucidate the involvement of the JAK-STAT signaling pathway in the pathogenesis of connective tissue diseases (CTDs). We also discuss the efficacy of the first- and second-generation JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, peficitinib, filgotinib, upadacitinib, solcitinib, itacitinib, decernotinib, R333, and pf-06651600) for CTDs including RA, systemic lupus erythematosus, dermatomyositis, systemic sclerosis, Sjögren's syndrome, and vasculitis, based on laboratory and clinical research findings. JAK inhibitors have great potential for the treatment of various CTDs by reducing multiple cytokine production and suppressing inflammation, with the advantages of rapid onset in an oral formulation and decreased corticosteroid dependence and the associated adverse events, especially in refractory cases. We also highlight the safety of novel JAK inhibitors, which can cause opportunistic infections, especially viral infections. Being a very recent therapeutic option, information regarding the safety of JAK inhibitors during pregnancy and for pediatric use is limited. However, it is recommended that JAK inhibitors should be avoided in pregnant and breastfeeding women. More clinical data, especially on highly selective inhibitors, are required to judge the efficacy and safety of JAK inhibition in CTDs.

100 项与索西替尼相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
系统性红斑狼疮	临床2期	韩国	GSK Plc	2013-03-01
系统性红斑狼疮	临床2期	爱沙尼亚	GSK Plc	2013-03-01
系统性红斑狼疮	临床2期	智利	GSK Plc	2013-03-01
系统性红斑狼疮	临床2期	南非	GSK Plc	2013-03-01
系统性红斑狼疮	临床2期	智利	GSK Plc	2013-03-01
系统性红斑狼疮	临床2期	韩国	GSK Plc	2013-03-01
系统性红斑狼疮	临床2期	爱沙尼亚	GSK Plc	2013-03-01
系统性红斑狼疮	临床2期	瑞典	GSK Plc	2013-03-01
系统性红斑狼疮	临床2期	瑞典	GSK Plc	2013-03-01
系统性红斑狼疮	临床2期	南非	GSK Plc	2013-03-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01782664 (CTgov)	临床2期	斑块状银屑病	68	Placebo	繭願鬱構夢壓鏇蓋選顧(襯製選顧願鑰憲觸衊廠) = 壓齋餘願鑰鑰獵觸鹽鬱構觸觸繭衊繭鹽窪鬱鹽 (鹹範憲構窪蓋獵築淵網, 壓艱繭糧獵構獵顧願簾 ~ 積襯襯鏇餘網醖築窪艱) 更多	-	2017-08-03
NCT01777256 (JAK115919, Pubmed \| Lupus) 人工标引	临床2期	系统性红斑狼疮	50	GSK2586184	(繭艱顧壓淵獵齋獵衊憲) = Shortly thereafter, significant safety data were identified, including elevated liver enzymes in six patients (one confirmed and one suspected case of Drug Reaction with Eosinophilia and Systemic Symptoms), leading to immediate dosing cessation. 簾蓋蓋範簾艱餘範網壓 (鹹艱餘鏇窪膚鏇醖衊醖 )	不佳	2016-11-01
NCT01777256 (JAK115919, Pubmed \| Lupus) 人工标引	临床2期	系统性红斑狼疮	50	Placebo		不佳	2016-11-01