Small Molecule TH-39 Potentially Targets Hec1/Nek2 Interaction and Exhibits Antitumor Efficacy in K562 Cells via G0/G1 Cell Cycle Arrest and Apoptosis Induction

Zhu, Yiping; Wei, Wei; Ye, Tinghong; Liu, Zhihao; Liu, Li; Luo, Yong; Zhang, Lidan; Gao, Chao; Wang, Ningyu; Yu, Luoting

doi:10.1159/000452546

Cited by 13 publications

(5 citation statements)

References 32 publications

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“…Therefore, this study exhibited the potential therapeutic efficacy of TH-39 as an anti-cancer compound for treatment of chronic myeloid leukemia (Fig. 5) [42].…”

Section: Structural Modification Of 2-amine Group Of 2-aminothiazole mentioning

confidence: 84%

Development and therapeutic potential of 2-aminothiazole derivatives in anticancer drug discovery

Alizadeh

Hashemi

2021

Med Chem Res

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Currently, the development of anticancer drug resistance is significantly restricted the clinical efficacy of the most commonly prescribed anticancer drug. Malignant disease is widely prevalent and considered to be the major challenges of this century, which concerns the medical community all over the world. Consequently, investigating small molecule antitumor agents, which could decrease drug resistance and reduce unpleasant side effect is more desirable. 2-aminothiazole scaffold has emerged as a promising scaffold in medicinal chemistry and drug discovery research. This nucleus is a fundamental part of some clinically applied anticancer drugs such as dasatinib and alpelisib. Literature survey documented that different 2aminothiazole analogs exhibited their potent and selective nanomolar inhibitory activity against a wide range of human cancerous cell lines such as breast, leukemia, lung, colon, CNS, melanoma, ovarian, renal, and prostate. In this paper, we have reviewed the progresses and structural modification of 2-aminothiazole to pursuit potent anticancers and also highlighted in vitro activities and in silico studies. The information will useful for future innovation.

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“…Therefore, this study exhibited the potential therapeutic efficacy of TH-39 as an anti-cancer compound for treatment of chronic myeloid leukemia (Fig. 5) [42].…”

Section: Structural Modification Of 2-amine Group Of 2-aminothiazole mentioning

confidence: 84%

Development and therapeutic potential of 2-aminothiazole derivatives in anticancer drug discovery

Alizadeh

Hashemi

2021

Med Chem Res

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“…D-Cyclins 1 and 2 (CCND1, CCND2) are key elements in the control of cell cycle progression from G1 to S phases [33,34]. It has been described that CCND1 overexpression is related with the arresting of cell proliferation [35].…”

Section: Discussionmentioning

confidence: 99%

Influence of Human Bone Marrow Mesenchymal Stem Cells Secretome from Acute Myeloid Leukemia Patients on the Proliferation and Death of K562 and K562-Lucena Leukemia Cell Lineages

de Freitas,

Levy,

Reichert

et al. 2024

IJMS

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Leukemias are among the most prevalent types of cancer worldwide. Bone marrow mesenchymal stem cells (MSCs) participate in the development of a suitable niche for hematopoietic stem cells, and are involved in the development of diseases such as leukemias, to a yet unknown extent. Here we described the effect of secretome of bone marrow MSCs obtained from healthy donors and from patients with acute myeloid leukemia (AML) on leukemic cell lineages, sensitive (K562) or resistant (K562-Lucena) to chemotherapy drugs. Cell proliferation, viability and death were evaluated, together with cell cycle, cytokine production and gene expression of ABC transporters and cyclins. The secretome of healthy MSCs decreased proliferation and viability of both K562 and K562‑Lucena cells; moreover, an increase in apoptosis and necrosis rates was observed, together with the activation of caspase 3/7, cell cycle arrest in G0/G1 phase and changes in expression of several ABC proteins and cyclins D1 and D2. These effects were not observed using the secretome of MSCs derived from AML patients. In conclusion, the secretome of healthy MSCs have the capacity to inhibit the development of leukemia cells, at least in the studied conditions. However, MSCs from AML patients seem to have lost this capacity, and could therefore contribute to the development of leukemia.

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“…For further analysis of the effect of Statmp-151, we performed Annexin V and PI double dye detection of MDA-MB-231 and 4T1 cells (Zhu et al, 2016). As shown in Figure 4A,B, Statmp-151 was able to induce breast cancer cell apoptosis in a dosedependent manner after treatment for 24 h compared to that in the control group.…”

Section: Statmp-151 Induced Apoptosis Of Breast Cancer Cellsmentioning

confidence: 97%

The Tetramethylpyrazine Derivative Statmp-151: A Novel Small Molecule Stat3 Inhibitor With Promising Activity Against Breast Cancer

et al. 2021

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Breast cancer is the most common malignancy in women and is a molecularly heterogeneous disease. Signal transducer and activator of transcription 3 (Stat3) is overexpressed and hyperactivated in a variety of human tumours, including breast cancer, thus representing a promising target for breast cancer treatment. In the present study, we evaluated the activities of a novel Stat3 inhibitor named Statmp-151 in the human breast cancer cell lines MCF-7 and MDA-MB-231 and the murine mammary carcinoma cell line 4T1. The in vitro results showed that Statmp-151 inhibited the proliferation of breast cancer cell lines in a dose- and time-dependent manner and suppressed the phosphorylation of Stat3 in a dose-dependent manner. Flow cytometry (FCM) assays revealed that Statmp-151 affected mitochondrial membrane potential and reactive oxygen species (ROS) production. Furthermore, Statmp-151 inhibited cell migration, as shown by analysis of the matrix metalloproteinases MMP2 and MMP9. Finally, in a 4T1 tumour-bearing mouse model, intraperitoneal injection of 30 mg/kg/day Statmp-151 significantly suppressed the growth of tumours without obvious toxicity. These results indicated that Statmp-151 might be a potential candidate for the treatment of breast cancer.

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Small Molecule TH-39 Potentially Targets Hec1/Nek2 Interaction and Exhibits Antitumor Efficacy in K562 Cells via G0/G1 Cell Cycle Arrest and Apoptosis Induction

Cited by 13 publications

References 32 publications

Development and therapeutic potential of 2-aminothiazole derivatives in anticancer drug discovery

Development and therapeutic potential of 2-aminothiazole derivatives in anticancer drug discovery

Influence of Human Bone Marrow Mesenchymal Stem Cells Secretome from Acute Myeloid Leukemia Patients on the Proliferation and Death of K562 and K562-Lucena Leukemia Cell Lineages

The Tetramethylpyrazine Derivative Statmp-151: A Novel Small Molecule Stat3 Inhibitor With Promising Activity Against Breast Cancer

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