ArticleInvestigational new drugs2008
A novel quinoline, MT477: suppresses cell signaling through Ras molecular pathway, inhibits PKC activity, and demonstrates in vivo anti-tumor activity against human carcinoma cell lines.
Article in Investigational new drugs, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 47 citations in OpenAlex.
- The antitumor natural product tanshinone IIA inhibits protein kinase C and acts synergistically with 17-AAG.Cell death & disease · 2018Article
- Drug screening on Hutchinson Gilford progeria pluripotent stem cells reveals aminopyrimidines as new modulators of farnesylation.Cell death & disease · 2016Article
- Novel cancer chemotherapy hits by molecular topology: dual Akt and Beta-catenin inhibitors.PloS one · 2015Article
- Article
- Andrographolide inhibits proliferation of human lung cancer cells and the related mechanisms.International journal of clinical and experimental medicine · 2014Article
- Primarily screening and analyzing ESTs differentially expressed in rats' primary liver cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2013Article
- Topological virtual screening: a way to find new compounds active in ulcerative colitis by inhibiting NF-κB.Molecular diversity · 2011Article
- MT103 inhibits tumor growth with minimal toxicity in murine model of lung carcinoma via induction of apoptosis.Investigational new drugs · 2011Article
- PKC-alpha inhibitor MT477 slows tumor growth with minimal toxicity in in vivo model of non-Ras-mutated cancer via induction of apoptosis.Investigational new drugs · 2011Article
- A review on molecular topology: applying graph theory to drug discovery and design.Die Naturwissenschaften · 2009Review
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MT477 is a novel thiopyrano[2,3-c]quinoline that has been identified using molecular topology screening as a potential anticancer drug with a high activity against protein kinase C (PKC) isoforms. The objective of the present study was to determine the mechanism of action of MT477 and its activity against human cancer cell lines. MT477 interfered with PKC activity as well as phosphorylation of Ras and ERK1/2 in H226 human lung carcinoma cells. It also induced poly-caspase-dependent apoptosis. MT477 had a dose-dependent (0.006 to 0.2 mM) inhibitory effect on cellular proliferation of H226, MCF-7, U87, LNCaP, A431 and A549 cancer cell lines as determined by in vitro proliferation assays. Two murine xenograft models of human A431 and H226 lung carcinoma were used to evaluate tumor response to intraperitoneal administration of MT477 (33 microg/kg, 100 microg/kg, and 1 mg/kg). Tumor growth was inhibited by 24.5% in A431 and 43.67% in H226 xenografts following MT477 treatment, compared to vehicle controls (p < 0.05). In conclusion, our empirical findings are consistent with molecular modeling of MT477's activity against PKC. We also found, however, that its mechanism of action occurs through suppressing Ras signaling, indicating that its effects on apoptosis and tumor growth in vivo may be mediated by Ras as well as PKC. We propose, therefore, that MT477 warrants further development as an anticancer drug.
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