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1 August 2015
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Cover Image
Cover Image
There is an unmet medical need for pharmacological inhibitors of signal transducer and activator of transcription 5a/b (Stat5a/b). Stat5a/b is critical for growth and progression of solid tumors and hematological malignancies, specifically prostate cancer and Bcr-Abl–driven leukemias. IST5-002, a lead compound of a small molecule inhibitor family of Stat5a/b, was identified through structure-based in-silico screening and medicinal chemistry. IST5-002 potently inhibited molecular events associated with Stat5a/b activation, reduced the expression of Stat5a/b-regulated genes and induced extensive apoptotic cell death in multiple models of prostate cancer and chronic myeloid leukemias in vitro, in vivo, and in patient samples. IST5-002 provides a lead structure for further chemical modifications for clinical development. For details, see article by Liao et al., on page 1777. - PDF Icon PDF LinkTable of Contents
ISSN 1535-7163
EISSN 1538-8514
Highlights
Review
Small Molecule Therapeutics
Structure-Based Screen Identifies a Potent Small Molecule Inhibitor of Stat5a/b with Therapeutic Potential for Prostate Cancer and Chronic Myeloid Leukemia
Zhiyong Liao; Lei Gu; Jenny Vergalli; Samanta A. Mariani; Marco De Dominici; Ravi K. Lokareddy; Ayush Dagvadorj; Puranik Purushottamachar; Peter A. McCue; Edouard Trabulsi; Costas D. Lallas; Shilpa Gupta; Elyse Ellsworth; Shauna Blackmon; Adam Ertel; Paolo Fortina; Benjamin Leiby; Guanjun Xia; Hallgeir Rui; David T. Hoang; Leonard G. Gomella; Gino Cingolani; Vincent Njar; Nagarajan Pattabiraman; Bruno Calabretta; Marja T. Nevalainen
Inhibition of mTORC2 Induces Cell-Cycle Arrest and Enhances the Cytotoxicity of Doxorubicin by Suppressing MDR1 Expression in HCC Cells
Bryan Wei Chen; Wei Chen; Hui Liang; Hao Liu; Chao Liang; Xiao Zhi; Li-qiang Hu; Xia-Zhen Yu; Tao Wei; Tao Ma; Fei Xue; Lei Zheng; Bin Zhao; Xin-Hua Feng; Xue-li Bai; Ting-bo Liang
Selective Inhibition of SIN3 Corepressor with Avermectins as a Novel Therapeutic Strategy in Triple-Negative Breast Cancer
Yeon-Jin Kwon; Kevin Petrie; Boris A. Leibovitch; Lei Zeng; Mihaly Mezei; Louise Howell; Veronica Gil; Rossitza Christova; Nidhi Bansal; Shuai Yang; Rajal Sharma; Edgardo V. Ariztia; Jessica Frankum; Rachel Brough; Yordan Sbirkov; Alan Ashworth; Christopher J. Lord; Arthur Zelent; Eduardo Farias; Ming-Ming Zhou; Samuel Waxman
MCL-1 Is a Key Determinant of Breast Cancer Cell Survival: Validation of MCL-1 Dependency Utilizing a Highly Selective Small Molecule Inhibitor
Yu Xiao; Paul Nimmer; George S. Sheppard; Milan Bruncko; Paul Hessler; Xin Lu; Lisa Roberts-Rapp; William N. Pappano; Steven W. Elmore; Andrew J. Souers; Joel D. Leverson; Darren C. Phillips
Large Molecule Therapeutics
Author Choice
23814, an Inhibitory Antibody of Ligand-Mediated Notch1 Activation, Modulates Angiogenesis and Inhibits Tumor Growth without Gastrointestinal Toxicity
Theresa Proia; Feng Jiang; Alisa Bell; Richard Nicoletti; Lingxin Kong; Kelly Kreuter; Laura Poling; William M. Winston; Meghan Flaherty; Solly Weiler; Samantha Perino; Ronan O'Hagan; Jie Lin; Jeno Gyuris; Heidi Okamura
Author Choice
Novel Anti-TM4SF1 Antibody–Drug Conjugates with Activity against Tumor Cells and Tumor Vasculature
Alberto Visintin; Kelly Knowlton; Edyta Tyminski; Chi-Iou Lin; Xiang Zheng; Kimberly Marquette; Sadhana Jain; Lioudmila Tchistiakova; Dan Li; Christopher J. O'Donnell; Andreas Maderna; Xianjun Cao; Robert Dunn; William B. Snyder; Anson K. Abraham; Mauricio Leal; Shoba Shetty; Anthony Barry; Leigh Zawel; Anthony J. Coyle; Harold F. Dvorak; Shou-Ching Jaminet
Cancer Biology and Signal Transduction
The TMPRSS2–ERG Gene Fusion Blocks XRCC4-Mediated Nonhomologous End-Joining Repair and Radiosensitizes Prostate Cancer Cells to PARP Inhibition
Payel Chatterjee; Gaurav S. Choudhary; Turkeyah Alswillah; Xiahui Xiong; Warren D. Heston; Cristina Magi-Galluzzi; Junran Zhang; Eric A. Klein; Alexandru Almasan
Inhibition of PI3K Pathway Reduces Invasiveness and Epithelial-to-Mesenchymal Transition in Squamous Lung Cancer Cell Lines Harboring PIK3CA Gene Alterations
Mara A. Bonelli; Andrea Cavazzoni; Francesca Saccani; Roberta R. Alfieri; Federico Quaini; Silvia La Monica; Maricla Galetti; Daniele Cretella; Cristina Caffarra; Denise Madeddu; Caterina Frati; Costanza Annamaria Lagrasta; Angela Falco; Pietro Rossetti; Claudia Fumarola; Marcello Tiseo; Pier Giorgio Petronini; Andrea Ardizzoni
The PI3K/Akt Pathway Regulates Oxygen Metabolism via Pyruvate Dehydrogenase (PDH)-E1α Phosphorylation
George J. Cerniglia; Souvik Dey; Shannon M. Gallagher-Colombo; Natalie A. Daurio; Stephen Tuttle; Theresa M. Busch; Alexander Lin; Ramon Sun; Tatiana V. Esipova; Sergei A. Vinogradov; Nicholas Denko; Constantinos Koumenis; Amit Maity
RacGAP1 Is a Novel Downstream Effector of E2F7-Dependent Resistance to Doxorubicin and Is Prognostic for Overall Survival in Squamous Cell Carcinoma
Mehlika Hazar-Rethinam; Lilia Merida de Long; Orla M. Gannon; Samuel Boros; Ana Cristina Vargas; Marcin Dzienis; Pamela Mukhopadhyay; Natalia Saenz-Ponce; Daniel D.E. Dantzic; Fiona Simpson; Nicholas A. Saunders
Companion Diagnostics and Cancer Biomarkers
Pilot Trial of Selecting Molecularly Guided Therapy for Patients with Non–V600 BRAF-Mutant Metastatic Melanoma: Experience of the SU2C/MRA Melanoma Dream Team
Patricia M. LoRusso; Scott A. Boerner; Mary Jo Pilat; Karen M. Forman; Clarice Y. Zuccaro; Jeffrey A. Kiefer; Winnie S. Liang; Sally Hunsberger; Bruce G. Redman; Svetomir N. Markovic; Aleksandar Sekulic; Alan H. Bryce; Richard W. Joseph; C. Lance Cowey; Leslie Anne Fecher; Jeffrey Alan Sosman; Paul B. Chapman; Gary K. Schwartz; David W. Craig; John D. Carpten; Jeffrey M. Trent
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