A novel tubulin inhibitor, 6h, suppresses tumor-associated angiogenesis and shows potent antitumor activity against non–small cell lung cancers

Li, Zi; Huang, Liancheng; Zhou, Tianhao; Chang, Xing; Yang, Yuying; Shi, Yani; Hao, Mingjing; Li, Zengqiang; Wu, Yingliang; Guan, Qı; Zhang, Weige; Zuo, Daiying

doi:10.1016/j.jbc.2022.102063

Cited by 9 publications

(4 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6C). Despite prior observations that CBSIs repress angiogenesis [17,41,42], no significant differences in microvessel density were observed among treatment groups (data not shown). Lung metastasis was evaluated as previously described [31].…”

Section: C and Ch-2-77 Induce Apoptosis And Repress Cell Migration An...contrasting

confidence: 88%

Biological activity of a stable 6-aryl-2-benzoyl-pyridine colchicine-binding site inhibitor, 60c, in metastatic, triple-negative breast cancer

Oluwalana,

Adeleye,

Krutilina

et al. 2024

Preprint

View full text Add to dashboard Cite

Background: Improving survival for patients diagnosed with metastatic disease and overcoming chemoresistance remain significant clinical challenges in treating breast cancer. Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by a lack of therapeutically targetable receptors (ER/PR/HER2). TNBC therapy includes a combination of cytotoxic chemotherapies, including microtubule-targeting agents (MTAs) like paclitaxel (taxane class) or eribulin (vinca class); however, there are currently no FDA-approved MTAs that bind to the colchicine-binding site. Approximately 70% of patients who initially respond to paclitaxel will develop taxane resistance (TxR). We previously reported that an orally bioavailable colchicine-binding site inhibitor (CBSI), VERU-111, inhibits TNBC tumor growth and treats pre-established metastatic disease. To further improve the potency and metabolic stability of VERU-111, we created next-generation derivatives of its scaffold, including 60c. Results: 60c shows improved in vitro potency compared to VERU-111 for taxane-sensitive and TxR TNBC models, and suppress TxR primary tumor growth without gross toxicity. 60c also suppressed the expansion of axillary lymph node metastases existing prior to treatment. Comparative analysis of excised organs for metastasis between 60c and VERU-111 suggested that 60c has unique anti-metastatic tropism. 60c completely suppressed metastases to the spleen and was more potent to reduce metastatic burden in the leg bones and kidney. In contrast, VERU-111 preferentially inhibited liver metastases and lung metastasis repression was similar. Together, these results position 60c as an additional promising CBSI for TNBC therapy, particularly for patients with TxR disease.

show abstract

Section: C and Ch-2-77 Induce Apoptosis And Repress Cell Migration An...contrasting

confidence: 88%

Biological activity of a stable 6-aryl-2-benzoyl-pyridine colchicine-binding site inhibitor, 60c, in metastatic, triple-negative breast cancer

Oluwalana,

Adeleye,

Krutilina

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…NSCLC is a highly vascularized solid tumor. TET2‐mutated immune cells facilitate tumor angiogenesis [96], further promoting metastasis by accelerating tumor cell invasion into the blood circulation [97]. The human microbiome has been documented to regulate angiogenesis through vascular endothelial growth factor (VEGF), endothelial cells (ECs), inflammatory factors, and inflammatory cells.…”

Section: Microbiome‐driven Mechanisms Of Lung Cancermentioning

confidence: 99%

The microbiome in the pathogenesis of lung cancer

Miao,

Qiu

2023

APMIS

View full text Add to dashboard Cite

As one of the malignant tumors with high incidence rate and high mortality, lung cancer seriously threatens the life safety of patients. Research shows that microorganisms are closely related to lung cancer. The microbiome is symbiotic with the host and plays a vital role in the functions of the human body. Microbiota dysbiosis is correlated with development of lung cancer. However, the underlying mechanisms are poorly understood. This paper summarizes the composition characteristics of the gut–lung axis microbiome and intratumoral microbiome in patients with lung cancer. We then expound five potential carcinogenic mechanisms based on microorganisms, such as genotoxicity, metabolism, inflammation, immune response, and angiogenesis. Next, we list three high‐throughput sequencing methods, and finally looks forward to the prospect of microorganisms as novel targets for early diagnosis and treatment of lung cancer.

show abstract

“…Non-small cell lung cancer is responsible for about 85 % of deaths among all lung cancers. [11] One of the characteristic features of the cancer is its high vascularity that eventually leads to metastasis to other organs and tissues of the body due to aggressive angiogenesis. Tubulin proteins provide structure to the cytoskeleton of cells and are responsible for microtubule formation during cell division.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Competitive and Noncompetitive Inhibitors of Alpha‐Glucosidase and Anticancer Agents

Ghani,

Syed,

Aljunidel

et al. 2024

Chemistry & Biodiversity

View full text Add to dashboard Cite

Heterocyclic chemistry displays a broad range of applications in medicinal chemistry that offers convenient and efficient routes for the synthesis of biologically active heterocyclic compounds. Imidazoles and phenylthiazoles are an important class of heterocycles that demonstrate a wide range of biological activities against various types of cancers, diabetes mellitus and pathogenic microorganisms. The functionalization of the imidazole moiety at various positions makes it more potent and a versatile synthetic intermediate. Imidazole‐containing drugs bear multiple therapeutic applications in the treatment of various diseases. The heterocyclic structure having oxothiazolidine moiety is an important scaffold present in various drugs, with potential for enzyme inhibition. Furthermore, phenyl thiazoles are reported to be potent apoptosis inducers with potential anticancer activity. In an effort to identify these heterocyclic compounds, we synthesized 26 new 4,5‐diphenyl‐1H‐imidazole, phenylthiazole, and oxothiazolidine heterocyclic analogues, some of which demonstrated potent α‐glucosidase inhibition since the enzyme is an important clinical target for treatment of diabetes mellitus. Additionally, the analogues also exhibited significant activity against various types of cancers including non‐small lung cancer. Kinetics and molecular docking of the target compounds with α‐glucosidase and tubulin protein identified specific groups and moieties that bear importance for designing of new antidiabetic and anticancer drugs, respectively.

show abstract

A novel tubulin inhibitor, 6h, suppresses tumor-associated angiogenesis and shows potent antitumor activity against non–small cell lung cancers

Cited by 9 publications

References 42 publications

Biological activity of a stable 6-aryl-2-benzoyl-pyridine colchicine-binding site inhibitor, 60c, in metastatic, triple-negative breast cancer

Biological activity of a stable 6-aryl-2-benzoyl-pyridine colchicine-binding site inhibitor, 60c, in metastatic, triple-negative breast cancer

The microbiome in the pathogenesis of lung cancer

Synthesis of Competitive and Noncompetitive Inhibitors of Alpha‐Glucosidase and Anticancer Agents

Contact Info

Product

Resources

About