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 x NEK2 相关的临床结果

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100 项与 Hec1 x NEK2 相关的转化医学

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0 项与 Hec1 x NEK2 相关的专利（医药）

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项与 Hec1 x NEK2 相关的文献（医药）

2023-10-09·Journal of biomolecular structure & dynamics

In-silico studies of 2-aminothiazole derivatives as anticancer agents by QSAR, molecular docking, MD simulation and MM-GBSA approaches.

Article

作者: Chitre, Trupti S ; Asgaonkar, Kalyani D ; Bhatambrekar, Aniket L ; Priya, D ; Hajare, Sayli G ; Lokwani, Deepak K ; Hirode, Purvaj V ; Pradhan, Kunal B ; Thorat, Shubhangi B ; Jain, Shirish P

Targeting Hec1/Nek2 is considered as crucial target for cancer treatment due to its significant role in cell proliferation. In pursuit of this, a series of twenty-five 2-aminothiazoles derivatives, along with their Hec1/Nek2 inhibitory activities were subjected to QSAR studies utilizing QSARINS software. The significant three descriptor QSAR model was generated, showing noteworthy statistical parameters: a correlation coefficient of cross validation leave one out (Q²_LOO) = 0.7965, coefficient of determination (R²) = 0.8436, (R²ext) = 0.6308, cross validation leave many out (Q2_LMO) = 0.7656, Concordance Correlation Coefficient (CCC_CV = 0.8875), CCC_tr = 0.9151, and CCC_ext = 0.0.7241. The descriptors integral to generated QSAR model include Moreau-Broto autocorrelation, which represents the spatial autocorrelation of a property along the molecular graph's topological structure (ATSC1i), Moran autocorrelation at lag 8, which is weighted by charges (MATS8c) and RPSA representing the total molecular surface area. It was noted that these descriptors significantly influence Hec1/Nek2 inhibitory activity of 2-aminothiazoles derivatives. New lead molecules were designed and predicted for their Hec1/Nek2 inhibitory activity based on the developed three descriptor model. Further, the ADMET and Molecular docking studies were carried out for these designed molecules. The three molecules were selected based on their docking score and further subjected for MD simulation studies. Post-MD MM-GBSA analysis were also performed to predicted the free binding energies of molecules. The study helped us to understand the key interactions between 2-aminothiazoles derivatives and Hec1/Nek2 protein that may be necessary to develop new lead molecules against cancer.Communicated by Ramaswamy H. Sarma.

2022-10-01·Fundamental & Clinical Pharmacology3区 · 医学

Role of NIMA‐related kinase 2 in lung cancer: Mechanisms and therapeutic prospects

3区 · 医学

Review

作者: Shah, Darshak ; Patel, Bhoomika M. ; Joshi, Mit

AbstractThe second most common cancer in both males and females is lung cancer. Chemotherapeutic resistance is the main problem associated with the treatment of lung cancer. Radiation therapy and surgery also produce recurrence in lung cancer patients; this shows the need to develop novel agents acting on new targets. A never in mitosis (NIMA)‐related kinase 2 (NEK2) is a serine/threonine kinase associated with the family of NIMA‐related kinase (NEK). NEK2 plays an important role in the regulating mitotic processes, such as centrosome duplication and separation, kinetochore attachment, spindle assembly checkpoint, and microtubule stabilization. Several in vitro, in vivo, and clinical studies have confirmed the overexpression of NEK2 in various types of cancers including lung cancer. Overexpression of NEK2 in non‐small cell lung cancer (NSCLC) cells increased cell proliferation and chromosomal instability. The overexpression of NEK2 results in the activation of its downstream proteins such as β‐catenin, MAD2, Hec1, rootletin, C‐Nap1, CDC20, Cep68, and Sgo1. Activation of the Akt, β‐catenin, and Wnt pathways could promote growth and metastasis of lung cancer cells. Such confirmation suggests that NEK2 is a novel target for treating many cancers including lung cancer. The current review provides an idea about functions and regulation of NEK2 and emphasizes about the role of NEK2 in lung cancer by discussing in vitro, in vivo, and clinical studies pertaining to the same.

2021-05-01·Experimental Biology and Medicine4区 · 医学

Mitotic kinases as drivers of the epithelial-to-mesenchymal transition and as therapeutic targets against breast cancers

4区 · 医学

Review

作者: Rivera-Rivera, Yainyrette ; Saavedra, Harold I ; Jusino, Shirley ; Colón-Marrero, Stephanie

Biological therapies against breast cancer patients with tumors positive for the estrogen and progesterone hormone receptors and Her2 amplification have greatly improved their survival. However, to date, there are no effective biological therapies against breast cancers that lack these three receptors or triple-negative breast cancers (TNBC). TNBC correlates with poor survival, in part because they relapse following chemo- and radio-therapies. TNBC is intrinsically aggressive since they have high mitotic indexes and tend to metastasize to the central nervous system. TNBCs are more likely to display centrosome amplification, an abnormal phenotype that results in defective mitotic spindles and abnormal cytokinesis, which culminate in aneuploidy and chromosome instability (known causes of tumor initiation and chemo-resistance). Besides their known role in cell cycle control, mitotic kinases have been also studied in different types of cancer including breast, especially in the context of epithelial-to-mesenchymal transition (EMT). EMT is a cellular process characterized by the loss of cell polarity, reorganization of the cytoskeleton, and signaling reprogramming (upregulation of mesenchymal genes and downregulation of epithelial genes). Previously, we and others have shown the effects of mitotic kinases like Nek2 and Mps1 (TTK) on EMT. In this review, we focus on Aurora A, Aurora B, Bub1, and highly expressed in cancer (Hec1) as novel targets for therapeutic interventions in breast cancer and their effects on EMT. We highlight the established relationships and interactions of these and other mitotic kinases, clinical trial studies involving mitotic kinases, and the importance that represents to develop drugs against these proteins as potential targets in the primary care therapy for TNBC.