ArticleInvestigational new drugs2014
CKD-516 displays vascular disrupting properties and enhances anti-tumor activity in combination with chemotherapy in a murine tumor model.
Article in Investigational new drugs, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 19 citations in OpenAlex.
- CKD-516 potentiates the anti-cancer activity of docetaxel against epidermal growth factor receptor tyrosine kinase inhibitor-resistant lung cancer.Toxicological research · 2023Article
- Review
- Anti-tumor efficacy of CKD-516 in combination with radiation in xenograft mouse model of lung squamous cell carcinoma.BMC cancer · 2020Article
- Phase I and pharmacokinetic study of the vascular-disrupting agent CKD-516 (NOV120401) in patients with refractory solid tumors.Pharmacology research & perspectives · 2020Article
- Proteomic analysis of gemcitabine-resistant pancreatic cancer cells reveals that microtubule-associated protein 2 upregulation associates with taxane treatment.Therapeutic advances in medical oncology · 2019Article
- Enhanced efficacy of radiofrequency ablation for hepatocellular carcinoma using a novel vascular disrupting agent, CKD-516.Hepatology international · 2017Article
- Phase I Study of CKD-516, a Novel Vascular Disrupting Agent, in Patients with Advanced Solid Tumors.Cancer research and treatment · 2016Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeCKD-516 is a benzophenone analog in which the B ring is modified by replacement with a carbonyl group. The study assessed CKD-516 as a vascular disrupting agent or anti-cancer drug.
methodsTo assess the effect of S516 on vascularization, we analyzed the effect on human umbilical vein endothelial cells (HUVECs). To determine the inhibition of cell proliferation of S516, we used H460 lung carcinoma cells. The alteration of microtubules was analyzed using immunoblot, RT-PCR and confocal imaging. To evaluate the anti-tumor effects of gemcitabine and/or CKD-516, H460 xenograft mice were treated with CKD-516 (2.5 mg/kg) and/or gemcitabine (40 mg/kg), and tumor growth was compared with vehicle-treated control. For histologic analysis, liver, spleen and tumor tissues from H460 xenograft mice were obtained 12 and 24 h after CKD-516 injection.
resultsCytoskeletal changes of HUVECs treated with 10 nM S516 were assessed by immunoblot and confocal imaging. S516 disrupted tubulin assembly and resulted in microtubule dysfunction, which induced cell cycle arrest (G2/M). S516 markedly enhanced the depolymerization of microtubules, perhaps due to the vascular disrupting properties of S516. Interestingly, S516 decreased the amount of total tubulin protein in HUVECs. Especially, S516 decreased mRNA expression α-tubulin (HUVECs only) and β-tubulin (HUVECs and H460 cells) at an early time point (4 h). Immunocytochemical analysis showed that S516 changed the cellular microtubule network and inhibited the formation of polymerized microtubules. Extensive central necrosis of tumors was evident by 12 h after treatment with CKD-516 (2.5 mg/kg, i.p.). In H460 xenografts, CKD-516 combined with gemcitabine significantly delayed tumor growth up to 57 % and 36 % as compared to control and gemcitabine alone, respectively.
conclusionCKD-516 is a novel agent with vascular disrupting properties and enhances anti-tumor activity in combination with chemotherapy.
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