In Silico Identification and In Vitro and In Vivo Validation of Anti-Psychotic Drug Fluspirilene as a Potential CDK2 Inhibitor and a Candidate Anti-Cancer Drug
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{"title"=>"In silico identification and in vitro and in vivo validation of anti-psychotic drug fluspirilene as a potential CDK2 inhibitor and a candidate anti-cancer drug", "type"=>"journal", "authors"=>[{"first_name"=>"Xi Nan", "last_name"=>"Shi", "scopus_author_id"=>"56799449700"}, {"first_name"=>"Hongjian", "last_name"=>"Li", "scopus_author_id"=>"48261247800"}, {"first_name"=>"Hong", "last_name"=>"Yao", "scopus_author_id"=>"56799648200"}, {"first_name"=>"Xu", "last_name"=>"Liu", "scopus_author_id"=>"56799338900"}, {"first_name"=>"Ling", "last_name"=>"Li", "scopus_author_id"=>"56799370100"}, {"first_name"=>"Kwong Sak", "last_name"=>"Leung", "scopus_author_id"=>"55650989500"}, {"first_name"=>"Hsiangfu", "last_name"=>"Kung", "scopus_author_id"=>"7402514190"}, {"first_name"=>"Di", "last_name"=>"Lu", "scopus_author_id"=>"56799587500"}, {"first_name"=>"Man Hon", "last_name"=>"Wong", "scopus_author_id"=>"23478640000"}, {"first_name"=>"Marie Chia Mi", "last_name"=>"Lin", "scopus_author_id"=>"7404816359"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"605749771", "pmid"=>"26147897", "doi"=>"10.1371/journal.pone.0132072", "issn"=>"19326203", "scopus"=>"2-s2.0-84940062416", "sgr"=>"84940062416"}, "id"=>"1773224c-7ea2-3db6-b3c8-af461e3b310b", "abstract"=>"Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Surgical resection and conventional chemotherapy and radiotherapy ultimately fail due to tumor recurrence and HCC's resistance. The development of novel therapies against HCC is thus urgently required. The cyclin-dependent kinase (CDK) pathways are important and well-established targets for cancer treatment. In particular, CDK2 is a key factor regulating the cell cycle G1 to S transition and a hallmark for cancers. In this study, we utilized our free and open-source protein-ligand docking software, idock, prospectively to identify potential CDK2 inhibitors from 4,311 FDA-approved small molecule drugs using a repurposing strategy and an ensemble docking methodology. Sorted by average idock score, nine compounds were purchased and tested in vitro. Among them, the anti-psychotic drug fluspirilene exhibited the highest anti-proliferative effect in human hepatocellular carcinoma HepG2 and Huh7 cells. We demonstrated for the first time that fluspirilene treatment significantly increased the percentage of cells in G1 phase, and decreased the expressions of CDK2, cyclin E and Rb, as well as the phosphorylations of CDK2 on Thr160 and Rb on Ser795. We also examined the anti-cancer effect of fluspirilene in vivo in BALB/C nude mice subcutaneously xenografted with human hepatocellular carcinoma Huh7 cells. Our results showed that oral fluspirilene treatment significantly inhibited tumor growth. Fluspirilene (15 mg/kg) exhibited strong anti-tumor activity, comparable to that of the leading cancer drug 5-fluorouracil (10 mg/kg). Moreover, the cocktail treatment with fluspirilene and 5-fluorouracil exhibited the highest therapeutic effect. These results suggested for the first time that fluspirilene is a potential CDK2 inhibitor and a candidate anti-cancer drug for the treatment of human hepatocellular carcinoma. In view of the fact that fluspirilene has a long history of safe human use, our discovery of fluspirilene as a potential anti-HCC drug may present an immediately applicable clinical therapy.", "link"=>"http://www.mendeley.com/research/silico-identification-vitro-vivo-validation-antipsychotic-drug-fluspirilene-potential-cdk2-inhibitor", "reader_count"=>20, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>3, "Student > Master"=>3, "Other"=>2, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>3, "Student > Master"=>3, "Other"=>2, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemistry"=>2, "Psychology"=>1, "Computer Science"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>2}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Argentina"=>1, "Malaysia"=>1, "Germany"=>1, "India"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2162985"], "description"=>"<p>Fluspirilene treatment at 30 <i>μ</i>M or 10 <i>μ</i>M concentration significantly increased the percentage of apoptosis in Huh7 and HepG2 cell lines compared to the control in a dose-and time-dependent manner (p < 0.05).</p>", "links"=>[], "tags"=>["fluspirilene treatment", "mice subcutaneously xenografted", "G 1 phase", "Huh 7 cells", "Potential CDK 2 Inhibitor", "CDK 2 inhibitor", "CDK 2 inhibitors", "hcc", "CDK 2", "hepatocellular carcinoma HepG 2", "balb", "ensemble docking methodology", "cell cycle G 1", "hepatocellular carcinoma Huh 7 cells"], "article_id"=>1474043, "categories"=>["Uncategorised"], "users"=>["Xi-Nan Shi", "Hongjian Li", "Hong Yao", "Xu Liu", "Ling Li", "Kwong-Sak Leung", "Hsiang-fu Kung", "Di Lu", "Man-Hon Wong", "Marie Chia-mi Lin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132072.g006", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_fluspirilene_on_the_apoptosis_of_HepG2_and_Huh7_hepatocellular_carcinoma_cells_/1474043", "title"=>"Effect of fluspirilene on the apoptosis of HepG2 and Huh7 hepatocellular carcinoma cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-06 03:04:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/2162999"], "description"=>"<p>The final score used to rank compounds was purposely designed to be the average score across these 44 structures of CDK2 so as to account for structural variability.</p><p>The 44 CDK2 holo structures used for ensemble docking.</p>", "links"=>[], "tags"=>["fluspirilene treatment", "mice subcutaneously xenografted", "G 1 phase", "Huh 7 cells", "Potential CDK 2 Inhibitor", "CDK 2 inhibitor", "CDK 2 inhibitors", "hcc", "CDK 2", "hepatocellular carcinoma HepG 2", "balb", "ensemble docking methodology", "cell cycle G 1", "hepatocellular carcinoma Huh 7 cells"], "article_id"=>1474057, "categories"=>["Uncategorised"], "users"=>["Xi-Nan Shi", "Hongjian Li", "Hong Yao", "Xu Liu", "Ling Li", "Kwong-Sak Leung", "Hsiang-fu Kung", "Di Lu", "Man-Hon Wong", "Marie Chia-mi Lin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132072.t001", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_44_CDK2_holo_structures_used_for_ensemble_docking_/1474057", "title"=>"The 44 CDK2 holo structures used for ensemble docking.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-07-06 03:04:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/2162998"], "description"=>"<p>CDK2 residues are rendered as lines colored by atom type. Fluspirilene is rendered as sticks colored by atom type. The interacting atoms and residues are labeled. The cyan, green and pink dashed lines represent hydrogen bonds, hydrophobic contacts and <i>π</i> interactions, respectively. This figure was created by iview [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132072#pone.0132072.ref016\" target=\"_blank\">16</a>].</p>", "links"=>[], "tags"=>["fluspirilene treatment", "mice subcutaneously xenografted", "G 1 phase", "Huh 7 cells", "Potential CDK 2 Inhibitor", "CDK 2 inhibitor", "CDK 2 inhibitors", "hcc", "CDK 2", "hepatocellular carcinoma HepG 2", "balb", "ensemble docking methodology", "cell cycle G 1", "hepatocellular carcinoma Huh 7 cells"], "article_id"=>1474056, "categories"=>["Uncategorised"], "users"=>["Xi-Nan Shi", "Hongjian Li", "Hong Yao", "Xu Liu", "Ling Li", "Kwong-Sak Leung", "Hsiang-fu Kung", "Di Lu", "Man-Hon Wong", "Marie Chia-mi Lin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132072.g009", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_predicted_conformation_of_fluspirilene_in_complex_with_CDK2_/1474056", "title"=>"The predicted conformation of fluspirilene in complex with CDK2.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-06 03:04:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/2162979"], "description"=>"<p>842 and 783 compounds were in the ranges of [−7.5, −8.0) and [−7.0, −7.5), respectively, constituting the two largest bins. 15 and 63 compounds were in the ranges of [−10.0, −10.5) and [−9.5, −10.0), respectively, constituting the two bins appropriate for selection of candidate drugs.</p>", "links"=>[], "tags"=>["fluspirilene treatment", "mice subcutaneously xenografted", "G 1 phase", "Huh 7 cells", "Potential CDK 2 Inhibitor", "CDK 2 inhibitor", "CDK 2 inhibitors", "hcc", "CDK 2", "hepatocellular carcinoma HepG 2", "balb", "ensemble docking methodology", "cell cycle G 1", "hepatocellular carcinoma Huh 7 cells"], "article_id"=>1474037, "categories"=>["Uncategorised"], "users"=>["Xi-Nan Shi", "Hongjian Li", "Hong Yao", "Xu Liu", "Ling Li", "Kwong-Sak Leung", "Hsiang-fu Kung", "Di Lu", "Man-Hon Wong", "Marie Chia-mi Lin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132072.g002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histogram_distribution_of_the_average_idock_score_of_the_4_914_compounds_/1474037", "title"=>"Histogram distribution of the average idock score of the 4,914 compounds.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-06 03:04:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/2162978"], "description"=>"<p>The RMSD distributions of pose 1 and pose m are shown in black and red, respectively. 10 and 28 points are below the baseline of RMSD = 2Å for pose 1 and pose m, respectively.</p>", "links"=>[], "tags"=>["fluspirilene treatment", "mice subcutaneously xenografted", "G 1 phase", "Huh 7 cells", "Potential CDK 2 Inhibitor", "CDK 2 inhibitor", "CDK 2 inhibitors", "hcc", "CDK 2", "hepatocellular carcinoma HepG 2", "balb", "ensemble docking methodology", "cell cycle G 1", "hepatocellular carcinoma Huh 7 cells"], "article_id"=>1474036, "categories"=>["Uncategorised"], "users"=>["Xi-Nan Shi", "Hongjian Li", "Hong Yao", "Xu Liu", "Ling Li", "Kwong-Sak Leung", "Hsiang-fu Kung", "Di Lu", "Man-Hon Wong", "Marie Chia-mi Lin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132072.g001", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Redocking_accuracy_of_idock_for_the_44_CDK2_complexes_/1474036", "title"=>"Redocking accuracy of idock for the 44 CDK2 complexes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-06 03:04:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/2163006", "https://ndownloader.figshare.com/files/2163007", "https://ndownloader.figshare.com/files/2163008", "https://ndownloader.figshare.com/files/2163009", "https://ndownloader.figshare.com/files/2163010", "https://ndownloader.figshare.com/files/2163011", "https://ndownloader.figshare.com/files/2163012", "https://ndownloader.figshare.com/files/2163013", "https://ndownloader.figshare.com/files/2163014", "https://ndownloader.figshare.com/files/2163015", "https://ndownloader.figshare.com/files/2163016"], "description"=>"<div><p>Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Surgical resection and conventional chemotherapy and radiotherapy ultimately fail due to tumor recurrence and HCC’s resistance. The development of novel therapies against HCC is thus urgently required. The cyclin-dependent kinase (CDK) pathways are important and well-established targets for cancer treatment. In particular, CDK2 is a key factor regulating the cell cycle G1 to S transition and a hallmark for cancers. In this study, we utilized our free and open-source protein-ligand docking software, idock, prospectively to identify potential CDK2 inhibitors from 4,311 FDA-approved small molecule drugs using a repurposing strategy and an ensemble docking methodology. Sorted by average idock score, nine compounds were purchased and tested <i>in vitro</i>. Among them, the anti-psychotic drug fluspirilene exhibited the highest anti-proliferative effect in human hepatocellular carcinoma HepG2 and Huh7 cells. We demonstrated for the first time that fluspirilene treatment significantly increased the percentage of cells in G1 phase, and decreased the expressions of CDK2, cyclin E and Rb, as well as the phosphorylations of CDK2 on Thr160 and Rb on Ser795. We also examined the anti-cancer effect of fluspirilene <i>in vivo</i> in BALB/C nude mice subcutaneously xenografted with human hepatocellular carcinoma Huh7 cells. Our results showed that oral fluspirilene treatment significantly inhibited tumor growth. Fluspirilene (15 mg/kg) exhibited strong anti-tumor activity, comparable to that of the leading cancer drug 5-fluorouracil (10 mg/kg). Moreover, the cocktail treatment with fluspirilene and 5-fluorouracil exhibited the highest therapeutic effect. These results suggested for the first time that fluspirilene is a potential CDK2 inhibitor and a candidate anti-cancer drug for the treatment of human hepatocellular carcinoma. In view of the fact that fluspirilene has a long history of safe human use, our discovery of fluspirilene as a potential anti-HCC drug may present an immediately applicable clinical therapy.</p></div>", "links"=>[], "tags"=>["fluspirilene treatment", "mice subcutaneously xenografted", "G 1 phase", "Huh 7 cells", "Potential CDK 2 Inhibitor", "CDK 2 inhibitor", "CDK 2 inhibitors", "hcc", "CDK 2", "hepatocellular carcinoma HepG 2", "balb", "ensemble docking methodology", "cell cycle G 1", "hepatocellular carcinoma Huh 7 cells"], "article_id"=>1474064, "categories"=>["Uncategorised"], "users"=>["Xi-Nan Shi", "Hongjian Li", "Hong Yao", "Xu Liu", "Ling Li", "Kwong-Sak Leung", "Hsiang-fu Kung", "Di Lu", "Man-Hon Wong", "Marie Chia-mi Lin"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0132072.s001", "https://dx.doi.org/10.1371/journal.pone.0132072.s002", "https://dx.doi.org/10.1371/journal.pone.0132072.s003", "https://dx.doi.org/10.1371/journal.pone.0132072.s004", "https://dx.doi.org/10.1371/journal.pone.0132072.s005", "https://dx.doi.org/10.1371/journal.pone.0132072.s006", "https://dx.doi.org/10.1371/journal.pone.0132072.s007", "https://dx.doi.org/10.1371/journal.pone.0132072.s008", "https://dx.doi.org/10.1371/journal.pone.0132072.s009", "https://dx.doi.org/10.1371/journal.pone.0132072.s010", "https://dx.doi.org/10.1371/journal.pone.0132072.s011"], "stats"=>{"downloads"=>32, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_Silico_Identification_and_In_Vitro_and_In_Vivo_Validation_of_Anti_Psychotic_Drug_Fluspirilene_as_a_Potential_CDK2_Inhibitor_and_a_Candidate_Anti_Cancer_Drug/1474064", "title"=>"<i>In Silico</i> Identification and <i>In Vitro</i> and <i>In Vivo</i> Validation of Anti-Psychotic Drug Fluspirilene as a Potential CDK2 Inhibitor and a Candidate Anti-Cancer Drug", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-07-06 03:04:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/2162987"], "description"=>"<p>Fluspirilene treatment decreased the expressions of CDK2, Rb, cyclin E, pho-CDK2 and pho-Rb, but not cyclin D1 and cyclin B1.</p>", "links"=>[], "tags"=>["fluspirilene treatment", "mice subcutaneously xenografted", "G 1 phase", "Huh 7 cells", "Potential CDK 2 Inhibitor", "CDK 2 inhibitor", "CDK 2 inhibitors", "hcc", "CDK 2", "hepatocellular carcinoma HepG 2", "balb", "ensemble docking methodology", "cell cycle G 1", "hepatocellular carcinoma Huh 7 cells"], "article_id"=>1474045, "categories"=>["Uncategorised"], "users"=>["Xi-Nan Shi", "Hongjian Li", "Hong Yao", "Xu Liu", "Ling Li", "Kwong-Sak Leung", "Hsiang-fu Kung", "Di Lu", "Man-Hon Wong", "Marie Chia-mi Lin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132072.g007", "stats"=>{"downloads"=>2, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_fluspirilene_treatment_on_the_expressions_of_important_proteins_involved_in_G1_to_S_transition_/1474045", "title"=>"Effect of fluspirilene treatment on the expressions of important proteins involved in G1-to-S transition.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-06 03:04:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/2163000"], "description"=>"<p>The idock score is an estimation of binding free energy in kcal/mol units. A more negative value implies a higher predicted binding affinity.</p><p>The nine top-scoring compounds purchased and tested <i>in vitro</i>.</p>", "links"=>[], "tags"=>["fluspirilene treatment", "mice subcutaneously xenografted", "G 1 phase", "Huh 7 cells", "Potential CDK 2 Inhibitor", "CDK 2 inhibitor", "CDK 2 inhibitors", "hcc", "CDK 2", "hepatocellular carcinoma HepG 2", "balb", "ensemble docking methodology", "cell cycle G 1", "hepatocellular carcinoma Huh 7 cells"], "article_id"=>1474058, "categories"=>["Uncategorised"], "users"=>["Xi-Nan Shi", "Hongjian Li", "Hong Yao", "Xu Liu", "Ling Li", "Kwong-Sak Leung", "Hsiang-fu Kung", "Di Lu", "Man-Hon Wong", "Marie Chia-mi Lin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132072.t002", "stats"=>{"downloads"=>3, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_nine_top_scoring_compounds_purchased_and_tested_in_vitro_/1474058", "title"=>"The nine top-scoring compounds purchased and tested <i>in vitro</i>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-07-06 03:04:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/2162981"], "description"=>"<p>(A) The nine compounds had discrepant cytotoxicity to HepG2 and Huh7 cell lines at different concentrationas, with fluspirilene exhibiting the highest cytotoxicity compared to the control (p < 0.05). (B) Fluspirilene exhibited dose- and time-dependent inhibition on cell viability in HepG2 and Huh7 cell lines compared to the control (p < 0.05).</p>", "links"=>[], "tags"=>["fluspirilene treatment", "mice subcutaneously xenografted", "G 1 phase", "Huh 7 cells", "Potential CDK 2 Inhibitor", "CDK 2 inhibitor", "CDK 2 inhibitors", "hcc", "CDK 2", "hepatocellular carcinoma HepG 2", "balb", "ensemble docking methodology", "cell cycle G 1", "hepatocellular carcinoma Huh 7 cells"], "article_id"=>1474039, "categories"=>["Uncategorised"], "users"=>["Xi-Nan Shi", "Hongjian Li", "Hong Yao", "Xu Liu", "Ling Li", "Kwong-Sak Leung", "Hsiang-fu Kung", "Di Lu", "Man-Hon Wong", "Marie Chia-mi Lin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132072.g004", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_the_nine_compounds_on_the_viability_of_HepG2_and_Huh7_hepatocellular_carcinoma_cells_/1474039", "title"=>"Effect of the nine compounds on the viability of HepG2 and Huh7 hepatocellular carcinoma cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-06 03:04:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/2162982"], "description"=>"<p>(A) Fluspirilene treatment dose- and time-dependently increased the percentage of cells in G1 phase. At 30 <i>μ</i>M or 10 <i>μ</i>M concentration, fluspirilene treatment continuously increased the percentage of G1 phase for 24 hours. (B) Cell cycle distribution at 24 hours after fluspirilene treatment. The increase of the G1 phase was accompanied by the simultaneous decrease of S phase.</p>", "links"=>[], "tags"=>["fluspirilene treatment", "mice subcutaneously xenografted", "G 1 phase", "Huh 7 cells", "Potential CDK 2 Inhibitor", "CDK 2 inhibitor", "CDK 2 inhibitors", "hcc", "CDK 2", "hepatocellular carcinoma HepG 2", "balb", "ensemble docking methodology", "cell cycle G 1", "hepatocellular carcinoma Huh 7 cells"], "article_id"=>1474040, "categories"=>["Uncategorised"], "users"=>["Xi-Nan Shi", "Hongjian Li", "Hong Yao", "Xu Liu", "Ling Li", "Kwong-Sak Leung", "Hsiang-fu Kung", "Di Lu", "Man-Hon Wong", "Marie Chia-mi Lin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132072.g005", "stats"=>{"downloads"=>0, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dose_and_time_dependent_effect_of_fluspirilene_treatment_on_cell_cycle_profile_of_G0_G1_S_and_G2_M_phases_/1474040", "title"=>"Dose- and time-dependent effect of fluspirilene treatment on cell cycle profile of G0-G1, S, and G2-M phases.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-06 03:04:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/2162980"], "description"=>"<p>This figure was created by RDKit (<a href=\"http://rdkit.org/\" target=\"_blank\">http://rdkit.org/</a>).</p>", "links"=>[], "tags"=>["fluspirilene treatment", "mice subcutaneously xenografted", "G 1 phase", "Huh 7 cells", "Potential CDK 2 Inhibitor", "CDK 2 inhibitor", "CDK 2 inhibitors", "hcc", "CDK 2", "hepatocellular carcinoma HepG 2", "balb", "ensemble docking methodology", "cell cycle G 1", "hepatocellular carcinoma Huh 7 cells"], "article_id"=>1474038, "categories"=>["Uncategorised"], "users"=>["Xi-Nan Shi", "Hongjian Li", "Hong Yao", "Xu Liu", "Ling Li", "Kwong-Sak Leung", "Hsiang-fu Kung", "Di Lu", "Man-Hon Wong", "Marie Chia-mi Lin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132072.g003", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_2D_structures_of_the_nine_top_scoring_compounds_/1474038", "title"=>"The 2D structures of the nine top-scoring compounds.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-06 03:04:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/2162991"], "description"=>"<p>The anti-tumor activity of oral fluspirilene (15 mg/kg) was comparable to that of 5-fluorouracil (10 mg/kg). Furthermore, their cocktail therapy exhibited synergistic therapeutic effect.</p>", "links"=>[], "tags"=>["fluspirilene treatment", "mice subcutaneously xenografted", "G 1 phase", "Huh 7 cells", "Potential CDK 2 Inhibitor", "CDK 2 inhibitor", "CDK 2 inhibitors", "hcc", "CDK 2", "hepatocellular carcinoma HepG 2", "balb", "ensemble docking methodology", "cell cycle G 1", "hepatocellular carcinoma Huh 7 cells"], "article_id"=>1474049, "categories"=>["Uncategorised"], "users"=>["Xi-Nan Shi", "Hongjian Li", "Hong Yao", "Xu Liu", "Ling Li", "Kwong-Sak Leung", "Hsiang-fu Kung", "Di Lu", "Man-Hon Wong", "Marie Chia-mi Lin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132072.g008", "stats"=>{"downloads"=>1, "page_views"=>33, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_oral_fluspirilene_treatment_and_intraperitoneal_injection_of_5_fluorouracil_on_tumor_growth_in_vivo_in_nude_mice_xenografted_with_Huh7_cells_/1474049", "title"=>"Effects of oral fluspirilene treatment and intraperitoneal injection of 5-fluorouracil on tumor growth <i>in vivo</i> in nude mice xenografted with Huh7 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-06 03:04:50"}

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  • {"unique-ip"=>"15", "full-text"=>"16", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"17", "full-text"=>"42", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"16", "full-text"=>"9", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"13", "full-text"=>"10", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"17", "full-text"=>"12", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"10", "cited-by"=>"1", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"8", "full-text"=>"40", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"17", "full-text"=>"12", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"15", "full-text"=>"16", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"19", "full-text"=>"32", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"16", "full-text"=>"37", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"15", "full-text"=>"11", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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