Reference Detail

Ref Type Journal Article
PMID (28004478)
Authors Zhou Y, Shan S, Li ZB, Xin LJ, Pan DS, Yang QJ, Liu YP, Yue XP, Liu XR, Gao JZ, Zhang JW, Ning ZQ, Lu XP
Title CS2164, a novel multi-target inhibitor against tumor angiogenesis, mitosis and chronic inflammation with anti-tumor potency.
Journal Cancer science
Vol 108
Issue 3
Date 2017 Mar
URL
Abstract Text Although inhibitors targeting tumor angiogenic pathway have provided improvement for clinical treatment in patients with various solid tumors, the still very limited anti-cancer efficacy and acquired drug resistance demand new agents that may offer better clinical benefits. In the effort to find a small molecule potentially targeting several key pathways for tumor development, we designed, discovered and evaluated a novel multi-kinase inhibitor, CS2164. CS2164 inhibited the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα and c-Kit), mitosis-related kinase Aurora B and chronic inflammation-related kinase CSF-1R in a high potency manner with the IC50 at a single-digit nanomolar range. Consequently, CS2164 displayed anti-angiogenic activities through suppression of VEGFR/PDGFR phosphorylation, inhibition of ligand-dependent cell proliferation and capillary tube formation, and prevention of vasculature formation in tumor tissues. CS2164 also showed induction of G2/M cell cycle arrest and suppression of cell proliferation in tumor tissues through the inhibition of Aurora B-mediated H3 phosphorylation. Furthermore, CS2164 demonstrated the inhibitory effect on CSF-1R phosphorylation that led to the suppression of ligand-stimulated monocyte-to-macrophage differentiation and reduced CSF-1R(+) cells in tumor tissues. The in vivo animal efficacy studies revealed that CS2164 induced remarkable regression or complete inhibition of tumor growth at well-tolerated oral doses in several human tumor xenograft models. Collectively, these results indicate that CS2164 is a highly selective multi-kinase inhibitor with potent anti-tumor activities against tumor angiogenesis, mitosis and chronic inflammation, which may provide the rationale for further clinical assessment of CS2164 as a therapeutic agent in the treatment of cancer.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Therapy Description
Chiauranib Chiauranib (CS2164) is a multi-kinase inhibitor that inhibits AURKB, CSF-1R, VEGFRs, KIT, and PDGFRA, resulting in decreased tumor growth and angiogenesis (PMID: 28004478).
Drug Name Trade Name Synonyms Drug Classes Drug Description
Chiauranib CS2164 Aurkb Inhibitors 17 CSF1R Inhibitor 22 KIT Inhibitor 48 PDGFR-alpha Inhibitor 7 VEGFR Inhibitor (Pan) 30 Chiauranib (CS2164) is a multi-kinase inhibitor that inhibits AURKB, CSF-1R, VEGFRs, KIT, and PDGFRA, resulting in decreased tumor growth and angiogenesis (PMID: 28004478).
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown colon cancer not applicable Chiauranib Preclinical - Cell line xenograft Actionable In a preclinical study, Chiauranib (CS2164) inhibited tumor growth in a colon cancer cell line xenograft model (PMID: 28004478). 28004478
Unknown unknown non-small cell lung carcinoma not applicable Chiauranib Preclinical - Cell line xenograft Actionable In a preclinical study, Chiauranib (CS2164) inhibited tumor growth in a non-small cell lung cancer cell line xenograft model (PMID: 28004478). 28004478
Unknown unknown hepatocellular carcinoma not applicable Chiauranib Preclinical - Cell line xenograft Actionable In a preclinical study, Chiauranib (CS2164) inhibited tumor growth in a hepatocellular carcinoma cell line xenograft model (PMID: 28004478). 28004478
Unknown unknown stomach cancer not applicable Chiauranib Preclinical - Cell line xenograft Actionable In a preclinical study, Chiauranib (CS2164) inhibited tumor growth in a gastric cancer cell line xenograft model (PMID: 28004478). 28004478