SB-743921(SB-743921) - 药物靶点：KIF11_专利_临床

概要

基本信息

药物类型

小分子化药

别名

GSK-921、SB 743921、SB-921

靶点

KIF11

作用方式

抑制剂

作用机制

KIF11抑制剂(驱动蛋白-1抑制剂)

治疗领域

肿瘤免疫系统疾病血液及淋巴系统疾病

在研适应症-

非在研适应症

晚期恶性实体瘤侵袭性非霍奇金淋巴瘤霍奇金淋巴瘤

原研机构

GSK Plc

在研机构-

非在研机构

权益机构

最高研发阶段无进展临床1/2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

登录后查看时间轴

结构/序列

分子式C31H33ClN2O3

InChIKeyPGXYIBJJCLWJST-MUUNZHRXSA-N

CAS号618430-39-0

关联

2

项与 SB-743921 相关的临床试验

NCT00343564

/ Completed临床1/2期

A Phase I-II Study to Determine the Safety, Pharmacokinetics and Potential Efficacy of Intravenous Administration of SB-743921 on Days 1 and 15 of a 28-Day Dosing Schedule in Patients With Non-Hodgkin Lymphoma and Hodgkin Lymphoma

This study was an early-phase trial arranged into two phases. The Phase I portion was a dose-escalation study designed to assess the safety, tolerability and to identify the maximum tolerated dose of SB-743921 in patients with Non-Hodgkin Lymphoma and Hodgkin Lymphoma. Phase II was intended to assess the activity, safety and tolerability of SB-743921 in patients with Indolent and Aggressive Non-Hodgkin's Lymphomas exclusively. The Phase II portion of the study was not initiated.

开始日期2006-04-01

申办/合作机构

Cytokinetics, Inc.

NCT00136513

/ Completed临床1期

A Phase I Study to Determine the Safety and Pharmacokinetics of Intravenous Administration of SB743921 on a Once Every 3 Week Schedule in Patients With Solid Tumors

The purpose of this study is to find a dose of SB-743921 in adult patients with solid tumors or lymphoma who have progressed on standard therapy or who have relapsed. SB-743921 is dosed by 1-hour intravenous infusion every 3 weeks. A patient may continue to receive treatment as long as they are benefiting from the treatment. Blood samples will be taken at specific times to measure the amount of the drug in your body at specific times after the drug is given. Blood samples will also be taken for lab tests such as complete blood counts and clinical chemistries. Physical exams will be performed before each treatment with SB-743921. During the treatment phase, the patients will undergo regular assessments for safety and clinical response.

开始日期2004-04-01

申办/合作机构

GSK Plc

100 项与 SB-743921 相关的临床结果

登录后查看更多信息

100 项与 SB-743921 相关的转化医学

登录后查看更多信息

100 项与 SB-743921 相关的专利（医药）

登录后查看更多信息

61

项与 SB-743921 相关的文献（医药）

2025-11-01·CELLULAR SIGNALLING

KIF11 promotes AML progression, and its inhibition by SB-743921 suppresses disease advancement through mitotic G2/M phase arrest

Article

作者: Yin, Hongli ; Gu, Mengmeng ; Wang, Jianwei ; Zhang, Fenli ; Wu, Di ; Yang, Yang ; Ding, Yifang ; Yang, Ying ; Cheng, Jia ; Zhang, Zimu ; Yu, Juanjuan ; Su, Xin ; Chen, Yanling ; Li, Zhiheng ; Cai, Linbo ; Li, Gen ; Wei, Yan ; Zhu, Qing ; Pan, Jian ; Li, Xiaolu ; Zhai, Zong ; Tao, Yanfang ; Xiao, Peifang

Acute myeloid leukaemia (AML) is a heterogeneous haematological malignancy. Despite advances in therapy, its prognosis remains poor with limited improvement in survival. KIF11 (Eg5), a kinesin motor protein essential for spindle dynamics during mitosis, interacts with microtubules. Inhibition of KIF11 disrupts spindle poles, impairs chromosome segregation, and induces mitotic arrest and apoptosis, making it a potential therapeutic target. SB-743921, a selective KIF11 inhibitor, has shown potent anti-tumour activity in various cancers. It effectively inhibits AML cell proliferation, induces cell cycle arrest, and suppresses tumour progression. In vitro, it exhibits potent cytotoxic activity against various AML cell lines, and KIF11 knockdown further confirms its pivotal role in AML. RNA sequencing reveals that SB-743921 downregulates key pathways (e.g. MYC, E2F and G2M). In vivo, SB-743921 delays tumour growth and prolongs survival in AML mice with minimal toxicity, thus supporting its clinical potential. These findings support further investigation on clinical applications and clinical strategies for addressing of this challenging disease.

2024-09-01·JOURNAL OF MOLECULAR STRUCTURE

Identification, characterization and biological studies of kinesine spindle protein inhibitor, benzo[b][1,4]oxazine-6-carboxamide derivative, via 3D-pharmacophore virtual screening

作者: Elseginy, Samia A.

Kinesin spindle protein (Eg5) has been widely studied, as an important target for developing chemotherapy drugs, due to its essential role in mitotic spindle formation in mitosis.In this study, we target a promising novel allosteric site involving α4 and α6 helixes, which is located 15 Å from the allosteric ispinesib site.An extensive 3D-Pharmacophore structure based virtual screening was conducted.Mol. docking was carried out to explore a library of com. mols.Eleven compounds were identified with diversity in their chem. scaffold.Biol. evaluation and MT ATPase assays revealed that compound 11 with scaffold N-(2- (2, 6 -dimethylphenoxy) phenyl) -3, 4-dihydro -3-oxo -2H-benzo[b][1,4]oxazine-6-carboxamide inhibits Eg5 activity at (IC₅₀ = 1.37 ± 0.15 μM).The chem. structure of compound 11 was confirmed by ¹H NMR and mass spectral data.The stability of compound 11 within the Eg5-ADP/ATP complex was investigated using mol. dynamic simulation technique.The free binding energy was calculated using MM/PBSA.

2024-06-01·Archives of biochemistry and biophysics

Binding patterns of inhibitors to different pockets of kinesin Eg5

Article

作者: Qin, Jingyu ; Huo, Ziling ; Ji, Qing ; Geng, Yizhao ; Zhang, Bingbing ; Jia, Ning

The kinesin-5 family member, Eg5, plays very important role in the mitosis. As a mitotic protein, Eg5 is the target of various mitotic inhibitors. There are two targeting pockets in the motor domain of Eg5, which locates in the α2/L5/α3 region and the α4/α6 region respectively. We investigated the interactions between the different inhibitors and the two binding pockets of Eg5 by using all-atom molecular dynamics method. Combined the conformational analysis with the free-energy calculation, the binding patterns of inhibitors to the two binding pockets are shown. The α2/L5/α3 pocket can be divided into 4 regions. The structures and binding conformations of inhibitors in region 1 and 2 are highly conserved. The shape of α4/α6 pocket is alterable. The space of this pocket in ADP-binding state of Eg5 is larger than that in ADP·Pi-binding state due to the limitation of a hydrogen bond formed in the ADP·Pi-binding state. The results of this investigation provide the structural basis of the inhibitor-Eg5 interaction and offer a reference for the Eg5-targeted drug design.

100 项与 SB-743921 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
侵袭性非霍奇金淋巴瘤	临床2期	美国	Cytokinetics, Inc.	2006-04-01
侵袭性非霍奇金淋巴瘤	临床2期	俄罗斯	Cytokinetics, Inc.	2006-04-01
霍奇金淋巴瘤	临床2期	美国	Cytokinetics, Inc.	2006-04-01
霍奇金淋巴瘤	临床2期	俄罗斯	Cytokinetics, Inc.	2006-04-01
晚期恶性实体瘤	临床1期	美国	GSK Plc	2004-04-01

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00343564 (Pubmed \| Leuk Lymphoma)	临床1/2期	淋巴瘤	-	SB-743921	窪淵餘遞範築蓋繭簾窪(鬱膚網襯壓構鏇膚簾繭) = 醖鹹簾齋蓋壓膚製糧範餘窪鹽襯鏇築淵築繭齋 (艱夢齋艱餘襯齋蓋願餘 )	-	2015-09-02
NCT00343564 (Pubmed \| Leuk Lymphoma)	临床1/2期	淋巴瘤	-	SB-743921 + G-CSF	窪淵餘遞範築蓋繭簾窪(鬱膚網襯壓構鏇膚簾繭) = 壓艱壓壓蓋獵選顧構淵餘窪鹽襯鏇築淵築繭齋 (艱夢齋艱餘襯齋蓋願餘 )	-	2015-09-02
ASCO2009	临床1/2期	霍奇金淋巴瘤 \| 非霍奇金淋巴瘤	51	SB-743921	構構鏇夢築觸鹽獵積夢(醖夢憲鹽構鑰鏇淵簾網) = 鑰構鹽壓觸鬱餘選壓鹽餘網繭糧醖網壓獵齋襯 (鏇遞網積壓襯獵鏇遞製 )	-	2009-05-20
ASCO2008	临床1/2期	霍奇金淋巴瘤	32	SB-743921	膚夢鏇繭構蓋齋築鑰鬱(壓衊積鑰淵範製築鏇觸) = 鹹憲簾選夢獵艱製網遞選窪構齋範壓鬱壓蓋蓋 (網餘壓網壓網鏇艱衊憲 ) 更多	-	2008-05-20
ASCO2006	临床1期	-	44	SB-743921	膚廠膚願衊鬱鹽蓋顧窪(構選壓鑰積製鏇憲艱範) = 鏇襯獵網積鏇觸繭遞範遞遞蓋觸糧積鹹遞積醖 (窪鏇繭壓積襯鹽膚襯獵 ) 更多	-	2006-06-20