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

靶点

KIF11

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

霍奇金淋巴瘤非霍奇金淋巴瘤实体瘤

原研机构

GSK Plc

在研机构-

非在研机构

Cytokinetics, Inc.

GSK Plc

最高研发阶段无进展临床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

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

21

项与 SB-743921 相关的文献（医药）

2024-02-14·mBio

Requirement of microtubules for secretion of a micronemal protein CpTSP4 in the invasive stage of the apicomplexan Cryptosporidium parvum

Article

作者: Wang, Chenchen ; Li, Meng ; Liu, Mingxiao ; Zhu, Guan ; Jiang, Peng ; Zhang, Ying ; Wang, Dongqiang ; Yin, Jigang ; Wu, Xiaodong

2023-10-10·Cancers

Inducing Mitotic Catastrophe as a Therapeutic Approach to Improve Outcomes in Ewing Sarcoma.

Article

作者: Puri, Rajni V ; Sabu, Priya ; Godwin, Andrew K ; Vishwakarma, Vikalp ; Hembruff, Stacey L ; Samuel, Glenson ; Gibbs, Benjamin K ; Turaga, Soumya M ; Pathak, Harsh B

Ewing sarcoma (EWS) is an aggressive pediatric malignancy of the bone and soft tissues in need of novel therapeutic options. To identify potential therapeutic targets, we focused on essential biological pathways that are upregulated by EWS-FLI1, the primary oncogenic driver of EWS, including mitotic proteins such as Aurora kinase A (AURKA) and kinesin family member 15 (KIF15) and its binding partner, targeting protein for Xklp2 (TPX2). KIF15/TPX2 cooperates with KIF11, a key mitotic kinesin essential for mitotic spindle orientation. Given the lack of clinical-grade KIF15/TPX2 inhibitors, we chose to target KIF11 (using SB-743921) in combination with AURKA (using VIC-1911) given that phosphorylation of KIF15^S1169 by Aurora A is required for its targeting to the spindle. In vitro, the drug combination demonstrated strong synergy (Bliss score ≥ 10) at nanomolar doses. Colony formation assay revealed significant reduction in plating efficiency (1-3%) and increased percentage accumulation of cells in the G2/M phase with the combination treatment (45-52%) upon cell cycle analysis, indicating mitotic arrest. In vivo studies in EWS xenograft mouse models showed significant tumor reduction and overall effectiveness: drug combination vs. vehicle control (p ≤ 0.01), SB-743921 (p ≤ 0.01) and VIC-1911 (p ≤ 0.05). Kaplan-Meier curves demonstrated superior overall survival with the combination compared to vehicle or monotherapy arms (p ≤ 0.0001).

2023-10-01·Biomaterials

A novel antibody-KSP inhibitor conjugate improves KSP inhibitor efficacy in vitro and in vivo.

Article

作者: Wang, Zihao ; Lu, Jing ; Fan, Shiyong ; Li, Xiao ; Jin, Ningyi ; Li, Yiquan ; Shang, Chao ; Dong, Yuchao ; Yu, Xiaoyang

Many clinical trials of kinesin spindle protein (KSP) inhibitors have failed due to issues such as high toxicity and a short circulation half-life in vivo. To address the limitations of current KSP inhibitors and thus broad its use in antitumor therapy, this study applied antibody-drug conjugate (ADC) technology to the KSP inhibitor SB-743921, which was coupled with the HER2-specific antibody trastuzumab using a cathepsin B-dependent valine-alanine (Val-Ala, VA) dipeptide-type linker to generate H2-921. Ex vivo and in vivo analyses of H2-921 showed an increased half-life of SB-743921 and prolonged contact time with tumor cells. Furthermore, H2-921 induced apoptosis and incomplete autophagy in HER2-positive cells. In the in vivo analyses, H2-921 had significant tumor-targeting properties, and tumor inhibition by H2-921 was greater than that by traditional KSP inhibitors but similar to that by the positive control drug T-DM1. In conclusion, this study describes a novel application of ADC technology that enhances the antitumor effects of a KSP inhibitor and thus may effectively address the poor clinical efficacy of KSP inhibitors.

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
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
非霍奇金淋巴瘤	临床2期	俄罗斯	Cytokinetics, Inc.	2006-04-01
非霍奇金淋巴瘤	临床2期	美国	Cytokinetics, Inc.	2006-04-01
实体瘤	临床2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


ASCO2009	临床1/2期	霍奇金淋巴瘤 \| 非霍奇金淋巴瘤	51	SB-743921	(醖簾觸簾淵醖鏇壓築醖) = 範壓顧夢憲繭糧鑰構願艱鏇構醖遞範鏇襯範蓋 (衊鏇構壓膚齋齋鏇觸淵 )	-	2009-05-20
ASCO2008	临床1/2期	霍奇金淋巴瘤	32	SB-743921	(醖夢鏇簾觸憲築築願廠) = 淵淵遞憲齋醖襯繭顧壓壓網願淵鑰鹽壓糧衊築 (窪鬱構遞憲憲鏇齋憲淵 ) 更多	-	2008-05-20
ASCO2006	临床1期	实体瘤	44	SB-743921	築築獵製夢鹹餘糧夢選(鹽醖鑰憲選簾網網廠壓) = 廠窪餘鏇選醖襯獵壓艱遞憲襯網製獵繭鑰襯蓋 (鹽鑰夢構願壓艱製鏇願 ) 更多	-	2006-06-20