{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T05:14:31Z","timestamp":1782537271900,"version":"3.54.5"},"reference-count":38,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,5,23]],"date-time":"2017-05-23T00:00:00Z","timestamp":1495497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2017,5,23]],"date-time":"2017-05-23T00:00:00Z","timestamp":1495497600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["30801404"],"award-info":[{"award-number":["30801404"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81273546"],"award-info":[{"award-number":["81273546"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:p>\n                    The\n                    <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>\n                    3K\u03b4 isoform (\n                    <jats:styled-content style=\"fixed-case\">PIK<\/jats:styled-content>\n                    3\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    ), also known as P110\u03b4, is predominately expressed in leukocytes and has been implicated as a potential target in the treatment of hematological malignancies. In this report, we detailed the pharmacologic properties of puquitinib, a novel, orally available\n                    <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>\n                    3K\u03b4 inhibitor. Puquitinib, which binds to the\n                    <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>\n                    \u2010binding pocket of\n                    <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>\n                    3K\u03b4, was highly selective and potent for\n                    <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>\n                    3K\u03b4 relative to other\n                    <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>\n                    3K isoforms and a panel of protein kinases, exhibiting low\u2010nanomolar biochemical and cellular inhibitory potencies. Additional cellular profiling demonstrated that puquitinib inhibited proliferation, induced G\n                    <jats:sub>1<\/jats:sub>\n                    \u2010phase cell\u2010cycle arrest and apoptosis in acute myeloid leukemia (\n                    <jats:styled-content style=\"fixed-case\">AML<\/jats:styled-content>\n                    ) cell lines, through downregulation of\n                    <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>\n                    3K signaling. In\n                    <jats:italic>in vivo<\/jats:italic>\n                    <jats:styled-content style=\"fixed-case\">AML<\/jats:styled-content>\n                    xenografts, puquitinib alone showed stronger efficacy than the well\u2010known p110\u03b4 inhibitor,\n                    <jats:styled-content style=\"fixed-case\">CAL<\/jats:styled-content>\n                    \u2010101, in association with a reduction in\n                    <jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content>\n                    and\n                    <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>\n                    phosphorylation in tumor tissues, without causing noticeable toxicity. Furthermore, the combination of puquitinib with cytotoxic drugs, especially daunorubicin, yielded significantly stronger antitumor efficacy compared with each agent alone. Thus, puquitinib is a promising agent with pharmacologic properties that are favorable for the treatment of\n                    <jats:styled-content style=\"fixed-case\">AML<\/jats:styled-content>\n                    .\n                  <\/jats:p>","DOI":"10.1111\/cas.13263","type":"journal-article","created":{"date-parts":[[2017,4,18]],"date-time":"2017-04-18T07:37:11Z","timestamp":1492501031000},"page":"1476-1484","source":"Crossref","is-referenced-by-count":26,"title":["Puquitinib, a novel orally available\n                    <scp>PI<\/scp>\n                    3K\u03b4 inhibitor, exhibits potent antitumor efficacy against acute myeloid leukemia"],"prefix":"10.1111","volume":"108","author":[{"given":"Chengying","family":"Xie","sequence":"first","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 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