title: 5-(Bis(3-(2-hydroxyethyl)-1H-indol-2-yl)methyl)-2-hydroxybenzoic acid (BHIMHA): showing a strategy of designing drug to block lung metastasis of tumors.
abstract: Early metastasis is still the most recalcitrant factor in the treatment of lung cancer patients. By analyzing the structures and comparing the docking scores of the known pharmacophores, the authors of this paper designed 5-(bis(3-(2-hydroxyethyl)-1H-indol-2-yl)methyl)-2-hydroxybenzoic acid (BHIMHA) as a promising lead compound to develop metastasis inhibitors. In vitro 5, 10, and 20 µM of BHIMHA concentration dependently inhibited the migration and invasion of A549 cells. In vivo 0.4, 2.0, and 8.9 µmol/kg of BHIMHA dose dependently inhibited the metastasis of LLC (Lewis Lung Carcinoma) toward lung. In vivo, 2 µmol/kg of BHIMHA showed additional actions of slowing the growth of the primary tumor of C57BL/6 mice and S180 mice as well as inhibiting xylene-induced ear edema of the mice. Therefore, BHIMHA simultaneously blocked tumor metastasis toward lung, slowed the primary tumor growth, and limited the inflammation. These pharmacological actions were correlated with the inhibition of PKCα and NF-κB expression.
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China; Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Taiping
authors.initials: T
authors.lastname: Gan
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China; Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China; Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China; Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China; Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Wu
authors.affiliation: Ludwig Center for Cancer Genetics and Therapeutics Kimmel Cancer Center, Johns Hopkins University School of Medicine, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China; Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Peng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000502:physiology; D009362:Neoplasm Metastasis / Q000517:prevention & control; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors* / Q000737:chemistry; D012459:Salicylates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C000611535:5-(bis(3-(2-hydroxyethyl)-1H-indol-2-yl)methyl)-2-hydroxybenzoic acid; D000970:Antineoplastic Agents; D007211:Indoles; D016328:NF-kappa B; D012459:Salicylates; D051571:Protein Kinase C-alpha
keywords: PKCα inhibitor; anti-inflammation; anticancer; invasion; lung metastasis; migration