预约演示

更新于：2025-05-07

Hec1

更新于：2025-05-07

基本信息

别名

HEC、HEC1、Highly expressed in cancer protein

+ [10]

简介

Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity (PubMed:12351790, PubMed:14654001, PubMed:14699129, PubMed:15062103, PubMed:15235793, PubMed:15239953, PubMed:15548592, PubMed:16732327, PubMed:30409912, PubMed:9315664). Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore (PubMed:15548592, PubMed:30409912). The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules (PubMed:23085020). Plays a role in chromosome congression and is essential for the end-on attachment of the kinetochores to spindle microtubules (PubMed:23891108, PubMed:25743205).

关联

项与 Hec1 相关的药物

T-1101

靶点

Hec1 x NEK2

作用机制

Hec1抑制剂 [+1]

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

INH1

靶点

Hec1

作用机制

Hec1抑制剂

在研机构

University of California, Irvine

原研机构

University of California, Irvine

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

TCR Mimic-Redirected T Cells Targeting NDC80(Eureka)

靶点

Hec1

作用机制

Hec1抑制剂

在研机构

Memorial Sloan Kettering Cancer Center [+1]

原研机构

Eureka Therapeutics, Inc.

在研适应症

血液肿瘤 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

项与 Hec1 相关的临床试验

NCT04685473

/ Active, not recruiting临床1期

A Phase I Study of Safety, Tolerability and Pharmacokinetics of T-1101 (Tosylate) Capsules in Subjects With Advanced Refractory Solid Tumors

T-1101 (Tosylate) is a new small molecule chemical entity being developed as a potential anti-cancer therapeutic by Taivex Therapeutics Corp. T-1101 (Tosylate) is a potent anti-cancer agent in numerous human cancer cell lines. In addition, oral administration of T-1101 (Tosylate) showed tumor growth inhibition in different mouse xenograft models of human cancers. In this study, safety, tolerability and pharmacokinetic (PK) of T-1101 (Tosylate) capsules will be evaluated and also the recommended dose and regimen(s) to initiate Phase 2 will be determined.

开始日期2021-01-07

申办/合作机构

泰纬生命科技股份有限公司

NCT03349073

/ Completed临床1期

An Extension Study of T-1101 (Tosylate) Administered Orally to Patients With Advanced Refractory Solid Tumors

T-1101 is a novel anti-cancer agent being developed by Taivex Therapeutics Corporation, and is being studied in a phase I dose escalation trial, protocol TAI-001. That trial's primary aim is to study the safety and tolerability of T-1101 (Tosylate) in subjects with advanced refractory solid tumors, and provides for a maximum of 2 cycles of treatment. At the end of 2 cycles of treatment, it is likely that some patients will be continuing to receive clinical benefit from T-1101 (Tosylate). The intention of this program is to enable these patients to continue to receive T-1101 (Tosylate) at the discretion of the principal investigators and Taivex Therapeutics Corporation.

开始日期2017-09-14

申办/合作机构

泰纬生命科技股份有限公司

NCT03195764

/ Terminated临床1期

A Phase I Safety and Tolerability Study of T-1101 (Tosylate) as a Oral Powder for Constitution (OPC) in Patients With Advanced Refractory Solid Tumors

T-1101 (Tosylate) is a new small molecule chemical entity being developed as a potential anti-cancer therapeutic by Taivex Therapeutics Corp. T-1101 (Tosylate) is a potent anti-cancer agent in numerous human cancer cell lines. In addition, oral administration of T-1101 (Tosylate) showed tumor growth inhibition in different mouse xenograft models of human cancers. In this study, safety, tolerability and PK of T-1101 (Tosylate) will be evaluated and also the recommended dose and regimen(s) to initiate Phase 2 will be determined.

开始日期2017-09-14

申办/合作机构

泰纬生命科技股份有限公司

100 项与 Hec1 相关的临床结果

登录后查看更多信息

100 项与 Hec1 相关的转化医学

登录后查看更多信息

0 项与 Hec1 相关的专利（医药）

登录后查看更多信息

778

项与 Hec1 相关的文献（医药）

2025-12-01·Chromosoma

Towards identification of a holocentromere marker in the lepidopteran model Spodoptera frugiperda

Article

作者: Legeai, Fabrice ; d'Alençon, Emmanuelle ; Gamble, Sally ; Gimenez, Sylvie ; Eychenne, Magali

Some insects have holocentric chromosomes, with multiple kinetochores rather than a single centromere. They also lack the CENP-A and CENP-C proteins, suggesting a kinetochore assembly process different from that of monocentric chromosomes. The homolog of CENP-T was recently shown to bind silent chromatin and to play a key role in kinetochore assembly in Bombyx mori, but its role in other insects with holocentric chromosomes is unknown. We identified kinetochore genes and analyzed their expression in Spodoptera frugiperda. We silenced the kinetochore genes cenp-L, cenp-S, cenp-X and ndc80 and searched for chromosome segregation defects in Sf9 cells. All kinetochore genes except cenp-S were more strongly expressed in gonadal than in somatic tissues. Immunofluorescence microscopy and RT-qPCR demonstrated the effective silencing of the target genes by transfection with dsRNA. In Sf9 cells depleted of CENP-L and NDC80, immunofluorescence microscopy revealed increases in mitotic index and in the proportion of cells with unaligned chromosomes or multipolar spindles. The depletion of CENP-S and CENP-X had no effect on mitotic index and no division defects were observed. This suggests that CENP-L and NDC80 play key roles in chromosome segregation, whereas the functions of CENP-S and CENP-X remain unknown. We have begun to characterize the kinetochore proteins (CENP-L, CENP-S, CENP-X, NDC80), a prerequisite for holocentromere identification in S. frugiperda. This study also provides the first information about the role, in Lepidoptera, of CENP-L, a protein essential to the structure of the constitutive centromere-associated network in species with monocentric chromosomes.

2025-04-01·Current Biology

Proximity-based activation of AURORA A by MPS1 potentiates error correction

Article

作者: Barisic, Marin ; Conde, Carlos ; Artes, Elena ; Barbosa, Francisca ; Bange, Tanja ; Pedroso, Paulo D ; Pinto, Inês ; Leça, Nelson ; Esposito Verza, Arianna ; Maresca, Thomas J ; Moura, Margarida ; Rodriguez-Calado, Sergi ; Sunkel, Claudio E

Faithful cell division relies on mitotic chromosomes becoming bioriented with each pair of sister kinetochores bound to microtubules oriented toward opposing spindle poles. Erroneous kinetochore-microtubule attachments often form during early mitosis but are destabilized through the phosphorylation of outer kinetochore proteins by centromeric AURORA B kinase (ABK) and centrosomal AURORA A kinase (AAK), thus allowing for re-establishment of attachments until biorientation is achieved.¹^,²^,³^,⁴^,⁵^,⁶^,⁷^,⁸^,⁹ MPS1-mediated phosphorylation of NDC80 has also been shown to directly weaken the kinetochore-microtubule interface in yeast.¹⁰ In human cells, MPS1 has been proposed to transiently accumulate at end-on attached kinetochores¹¹ and phosphorylate SKA3 to promote microtubule release.¹² Whether MPS1 directly targets NDC80 and/or promotes the activity of AURORA kinases in metazoans remains unclear. Here, we report a novel mechanism involving communication between kinetochores and centrosomes, wherein MPS1 acts upstream of AAK to promote error correction. MPS1 on pole-proximal kinetochores phosphorylates the C-lobe of AAK, thereby increasing its activation at centrosomes. This proximity-based activation ensures the establishment of a robust AAK activity gradient that locally destabilizes mal-oriented kinetochores near spindle poles. Accordingly, MPS1 depletion from Drosophila cells causes severe chromosome misalignment and erroneous kinetochore-microtubule attachments, which can be rescued by tethering either MPS1 or constitutively active AAK mutants to centrosomes. Proximity-based activation of AAK by MPS1 also occurs in human cells to promote AAK-mediated phosphorylation of the NDC80 N-terminal tail. These findings uncover an MPS1-AAK crosstalk that is required for efficient error correction, showcasing the ability of kinetochores to modulate centrosome outputs to ensure proper chromosome segregation.

2025-02-18·Science Signaling

Sustained chromosomal passenger complex activity preserves the pluripotency of human embryonic carcinoma cells

Article

作者: Ishimaru, Naozumi ; Arakaki, Rieko ; Mouri, Yasuhiro ; Guardavaccaro, Daniele ; Murano, Kensaku ; Kudo, Yasusei ; Shao, Wenhua ; Ruppert, Jan G. ; Tsunematsu, Takaaki ; Pagano, Michele

Human embryonic carcinoma (hEC) cells are derived from teratocarcinomas, exhibit robust proliferation, have a high differentiation potential, are the malignant counterparts of human embryonic stem cells (hESCs), and are considered hESC-like. The chromosomal passenger complex (CPC), made up of the microtuble binding protein Borealin, the kinase Aurora-B, the CPC-stabilizing inner centromere protein (INCENP), and the inhibitor of apoptosis family member Survivin, regulates cell division and is active exclusively during mitosis in somatic cells. The anaphase-promoting complex/cyclosome and its cofactor Cdh1 (APC/C Cdh1 ) is a ubiquitylating complex that catalyzes the degradation of Aurora-B and Borealin in somatic cells but has low activity during interphase in hESCs. Here, we found that Borealin and Aurora-B exhibited sustained stability throughout the cell cycle of hEC cells due to low APC/C Cdh1 activity. In contrast with somatic cells, CPC activity persisted across the cell cycle of hEC cells because of diminished APC/C Cdh1 activity. Disrupting the CPC complex by depleting its constituents triggered spontaneous differentiation in hEC cells. As hEC cells differentiated, APC/C Cdh1 activation curtailed CPC activity. Inactivating the CPC by pharmacologically inhibiting Aurora-B induced hEC cell differentiation by activating the epithelial-to-mesenchymal transition (EMT) program. Hence, APC/C Cdh1 -mediated termination of CPC activity triggered hEC cell differentiation. Collectively, these findings demonstrate a role for the CPC in governing hESC cell fate.

项与 Hec1 相关的新闻（医药）

2023-11-05

·生物探索

Cell Discovery | 人类卵子非整倍体高发生率的潜在机理

非整倍体严重损害女性生育能力，增加出生缺陷的发生率。即使是来自年轻女性的人类卵子的非整倍体率也明显高于其他哺乳动物。然而，人类卵子非整倍体高发生率的内在遗传因素在很大程度上仍然未知。2023年10月24日，复旦大学王磊、武田宇及桑庆共同通讯在Cell Discovery（IF=34）在线发表题为“Ectopic expression of human TUBB8 leads to increased aneuploidy in mouse oocytes”的研究论文，该研究发现人类TUBB8 在小鼠卵母细胞中的异位表达通过引起着丝点微管(K-MT)附着缺陷增加了非整倍体的发生率。在表达TUBB8的小鼠卵母细胞中，拉伸的二价体受到的张力较小，导致在I中期后期，AURKB/C对HEC1的持续磷酸化状态损害了已建立的正确的K-MT附着。该研究发现，没有C端尾的TUBB8异位表达通过减少错误的K-MT附着而降低了非整倍体率。重要的是，在复发性流产患者中发现了TUBB8 C端尾部的变异。小鼠卵母细胞中TUBB8变体的异位表达也会损害K-MT附着并增加非整倍体率。总之，该研究为人类卵子非整倍体的生理机制以及反复流产的病理生理机制提供了新的认识。人类卵子经常含有不正确数量的染色体，这种情况被称为非整倍体，它是女性不育/生育能力低下、反复流产和出生缺陷的主要原因之一。20 ~ 32岁女性非整倍体卵的发生率为20% ~ 30%，高于许多其他生殖年龄物种，如小鼠(1% ~ 4%)、猪(3% ~ 10%)、牛(5.8% ~ 7.1%)、马(~15.6%)和恒河猴(7.1% ~ 18.4%)。虽然在人类卵子中观察到高频率的非整倍体，但在生理条件下导致人类卵子高频率非整倍体的具体遗传因素和确切机制仍有待阐明。人类卵子的非整倍性是由减数分裂I中染色体分离错误引起的。研究表明，瞬态三极纺锤体诱导的三向分裂可能导致后期染色体分离容易出错。人类卵母细胞中缺乏KIFC1被认为是其不稳定和多纺锤极的原因，导致非整倍性增加。此外，短暂的不稳定多极纺锤体会导致人类卵母细胞中异常的着丝点微管(K-MT)附着，从而导致染色体误分离。成对的着丝点由来自相对纺锤极的微管连接，以确保准确的染色体分离。稳定的着丝点微管(也称为k-纤维)是正确的K-MT附着所必需的。TUBB8的异位表达增加了小鼠卵母细胞非整倍体的发生率（图源自Cell Discovery ）微管通常由保守的α和β-微管蛋白异二聚体组成。人β-微管蛋白由9个同型组成，包括TUBB1、TUBB2A、TUBB2B、TUBB3、TUBB4A、TUBB4B、TUBB5、TUBB6和TUBB8。除TUBB8外，在小鼠卵母细胞中也检测到8种。之前证明了TUBB8在人类卵母细胞纺锤体中是唯一表达的，纺锤体由含有显性β-微管蛋白同型编码的TUBB821的异源二聚体聚合而成。而小鼠卵母细胞纺锤体主要由β-微管蛋白同型组成，如TUBB3、TUBB4B、TUBB5和TUBB6。此外，之前的研究表明，TUBB8变异患者表现出由广泛的纺锤体缺陷引起的卵母细胞减数分裂停滞、早期胚胎发育停滞或非整倍体。该研究证明了灵长类特异性TUBB8的异位表达诱导小鼠卵母细胞非整倍体的升级，并进一步阐明了TUBB8诱导非整倍体的机制。此外，研究发现TUBB8 C端尾部的变异更容易产生非整倍体卵子，并与复发性流产有关。这些结果为人类卵子高频率非整倍体的生理和病理生理机制提供了新的认识。文章来源“iNature”责编|探索君排版|探索君参考文献：Dong, J., Jin, L., Bao, S. et al. Ectopic expression of human TUBB8 leads to increased aneuploidy in mouse oocytes. Cell Discov 9, 105 (2023). https://doi.org/10.1038/s41421-023-00599-zEnd往期精选围观历史性突破！不需卵子和精子就可以合成人类胚胎热文富豪用儿子血浆“回春”科学吗？Science：血液牛磺酸缺乏驱动衰老热文世界首例！35岁的她，通过机器人操刀移植的子宫，成功诞下宝宝热文为了避免心脏骤停，53岁的他成为“第一个”植入开创性除颤器的心脏病患者热文首次披露！175家生物制药公司的薪资数据：薪资中位数达20万美元点击“阅读原文”，了解更多~

临床1期临床结果

2022-06-06

·BioSpace

Eureka Therapeutics Announces Publication of Study Demonstrating Broad Anti-Tumor Activity of TCR Mimic-Redirected T Cells Targeting NDC80

June 6, 2022 12:05 UTC EMERYVILLE, Calif.--(BUSINESS WIRE)-- Eureka Therapeutics, Inc., a clinical-stage biotechnology company developing novel T cell therapies to treat solid tumors, today announced the publication of a preclinical study in blood entitled “A TCR Mimic CAR T Cell Specific for NDC80 Is Broadly Reactive With Solid Tumors and Hematological Malignancies”. The study was led by Dr. Cheng Liu, President & Chief Executive Officer of Eureka and Dr. Martin Klatt and Dr. David Scheinberg of Memorial Sloan Kettering Cancer Center (MSK). Chimeric antigen receptor (CAR) T cells represent a novel class of FDA-approved drugs with high efficacy against refractory B cell-derived malignancies. However, target identification and selection for CAR T cell therapy remains challenging as most cell surface proteins are not cancer-specific and therefore often not adaptable for CAR T cell therapy. In contrast, many intracellular proteins are highly tumor-specific and targetable after being presented on the cell surface by human leukocyte antigen (HLA) complexes in the form of peptide-MHC complexes. T cell receptor mimic (TCRm) antibodies can recognize peptide-MHC complexes similarly to TCRs, but with the versatility and applicability of an antibody. In collaboration with MSK, Eureka scientists used its E-ALPHA® platform to identify TCRm antibodies that target the NDC80-derived complex. NDC80 is an intracellular protein over-expressed in multiple tumor types such as ALL, AML, lymphoma, melanoma, mesothelioma, pancreatic and thyroid cancer. In the study, anti-NDC80 TCRm-redirected T cells demonstrated high specificity in recognizing and killing multiple cancer cell lines. Moreover, no toxicities to healthy leukocytes and hematopoietic stem cells were observed. “TCR mimic antibodies can unlock the potential of T-cell therapies by targeting intracellular proteins that are presently not druggable by conventional antibodies or conventional CAR-T cells that target cell surface proteins,” said Dr. Cheng Liu, Founder and CEO, Eureka Therapeutics. “We are excited by the study and look forward to seeing the expanded use of TCR mimic antibodies in other cancer types.” About Eureka Therapeutics Eureka Therapeutics, Inc. is a privately-held clinical-stage biotechnology company focusing on developing novel T cell therapies to treat cancers. Its core technology centers around its proprietary ARTEMIS® cell receptor platform and E-ALPHA® antibody discovery platform for the discovery and development of potentially safer and more effective T cell therapies for the treatment of solid tumors and hematologic malignancies. The Company currently has two clinical programs, ET140203 (ARYA1 and ARYA2) and ECT204 (ARYA3), in Phase I/II US trials in patients with advanced liver cancer. Eureka Therapeutics, Inc. is headquartered in the San Francisco Bay Area. For more information on Eureka, please visit .

抗体细胞疗法