title: Discovery of a Highly Selective STK16 Kinase Inhibitor.
abstract: STK16, a serine/threonine protein kinase, is ubiquitously expressed and is conserved among all eukaryotes. STK16 has been implicated to function in a variety of cellular processes such as VEGF and cargo secretion, but the pathways through which these effects are mediated remain to be elucidated. Through screening of our focused library of kinase inhibitors, we discovered a highly selective ATP competitive inhibitor, STK16-IN-1, which exhibits potent inhibitory activity against STK16 kinase (IC50: 0.295 μM) with excellent selectivity across the kinome as assessed using the KinomeScan profiling assay (S score (1) = 0.0). In MCF-7 cells, treatment with STK16-IN-1 results in a reduction in cell number and accumulation of binucleated cells, which can be recapitulated by RNAi knockdown of STK16. Co-treatment of STK16-IN-1 with chemotherapeutics such as cisplatin, doxorubicin, colchicine, and paclitaxel results in a slight potentiation of the antiproliferative effects of the chemotherapeutics. STK16-IN-1 provides a useful tool compound for further elucidating the biological functions of STK16.
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences , 350 Shushanhu Road, P.O. Box 1110, Hefei, Anhui 230031, People's Republic of China.|University of Science and Technology of China , Hefei, Anhui 230036, People's Republic of China.
authors.forename: Feiyang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School , 250 Longwood Ave, SGM 628, Boston, Massachusetts 02115, United States.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wang
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences , 350 Shushanhu Road, P.O. Box 1110, Hefei, Anhui 230031, People's Republic of China.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Yang
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences , 350 Shushanhu Road, P.O. Box 1110, Hefei, Anhui 230031, People's Republic of China.|CHMFL-HCMTC Target Therapy Joint Laboratory , Shushanhu Road, Hefei, Anhui 230031, People's Republic of China.
authors.forename: Binhua
authors.initials: B
authors.lastname: Li
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences , 350 Shushanhu Road, P.O. Box 1110, Hefei, Anhui 230031, People's Republic of China.|University of Science and Technology of China , Hefei, Anhui 230036, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences , 350 Shushanhu Road, P.O. Box 1110, Hefei, Anhui 230031, People's Republic of China.|CHMFL-HCMTC Target Therapy Joint Laboratory , Shushanhu Road, Hefei, Anhui 230031, People's Republic of China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Qi
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences , 350 Shushanhu Road, P.O. Box 1110, Hefei, Anhui 230031, People's Republic of China.|CHMFL-HCMTC Target Therapy Joint Laboratory , Shushanhu Road, Hefei, Anhui 230031, People's Republic of China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences , 350 Shushanhu Road, P.O. Box 1110, Hefei, Anhui 230031, People's Republic of China.|University of Science and Technology of China , Hefei, Anhui 230036, People's Republic of China.
authors.forename: Xiaochuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences , 350 Shushanhu Road, P.O. Box 1110, Hefei, Anhui 230031, People's Republic of China.|University of Science and Technology of China , Hefei, Anhui 230036, People's Republic of China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Yu
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences , 350 Shushanhu Road, P.O. Box 1110, Hefei, Anhui 230031, People's Republic of China.|CHMFL-HCMTC Target Therapy Joint Laboratory , Shushanhu Road, Hefei, Anhui 230031, People's Republic of China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Wang
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences , 350 Shushanhu Road, P.O. Box 1110, Hefei, Anhui 230031, People's Republic of China.|CHMFL-HCMTC Target Therapy Joint Laboratory , Shushanhu Road, Hefei, Anhui 230031, People's Republic of China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences , 350 Shushanhu Road, P.O. Box 1110, Hefei, Anhui 230031, People's Republic of China.|University of Science and Technology of China , Hefei, Anhui 230036, People's Republic of China.
authors.forename: Aoli
authors.initials: A
authors.lastname: Wang
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences , 350 Shushanhu Road, P.O. Box 1110, Hefei, Anhui 230031, People's Republic of China.|CHMFL-HCMTC Target Therapy Joint Laboratory , Shushanhu Road, Hefei, Anhui 230031, People's Republic of China.
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences , 350 Shushanhu Road, P.O. Box 1110, Hefei, Anhui 230031, People's Republic of China.|CHMFL-HCMTC Target Therapy Joint Laboratory , Shushanhu Road, Hefei, Anhui 230031, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School , 250 Longwood Ave, SGM 628, Boston, Massachusetts 02115, United States.
authors.forename: Nathanael S
authors.initials: NS
authors.lastname: Gray
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences , 350 Shushanhu Road, P.O. Box 1110, Hefei, Anhui 230031, People's Republic of China.|CHMFL-HCMTC Target Therapy Joint Laboratory , Shushanhu Road, Hefei, Anhui 230031, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences , 350 Shushanhu Road, P.O. Box 1110, Hefei, Anhui 230031, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences , 350 Shushanhu Road, P.O. Box 1110, Hefei, Anhui 230031, People's Republic of China.|University of Science and Technology of China , Hefei, Anhui 230036, People's Republic of China.|CHMFL-HCMTC Target Therapy Joint Laboratory , Shushanhu Road, Hefei, Anhui 230031, People's Republic of China.|Hefei Science Center, Chinese Academy of Sciences , Shushanhu Road, Hefei, Anhui 230031, People's Republic of China.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000495:Allosteric Site; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D003078:Colchicine / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D059565:G2 Phase Cell Cycle Checkpoints; D055785:Gene Knockdown Techniques; D006801:Humans; D062105:Molecular Docking Simulation; D009287:Naphthyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D017239:Paclitaxel / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D009287:Naphthyridines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; C000622569:STK16-IN-1; D014157:Transcription Factors; D004317:Doxorubicin; D017346:Protein Serine-Threonine Kinases; C418980:STK16 protein, human; D017239:Paclitaxel; D002945:Cisplatin; D003078:Colchicine