scholarly journals Induction of apoptosis and antitumor effects of a small molecule inhibitor of Bcl-2 and Bcl-xl, gossypol acetate, in multiple myeloma in vitro and in vivo

2013 ◽  
Vol 30 (2) ◽  
pp. 731-738 ◽  
Author(s):  
JIE LIN ◽  
YONGJI WU ◽  
DAJUN YANG ◽  
YONGQIANG ZHAO
Keyword(s):  
Multiple Myeloma ◽  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Antitumor Effects ◽  
Molecule Inhibitor ◽  
Induction Of Apoptosis

scholarly journals A Novel Small-Molecule Inhibitor of Protein Kinase D Blocks Pancreatic Cancer Growth In vitro and In vivo

2010 ◽  
Vol 9 (5) ◽  
pp. 1136-1146 ◽  
Author(s):  
Kuzhuvelil B. Harikumar ◽  
Ajaikumar B. Kunnumakkara ◽  
Nobuo Ochi ◽  
Zhimin Tong ◽  
Amit Deorukhkar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Protein Kinase ◽  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Cancer Growth ◽  
Protein Kinase D ◽  
Molecule Inhibitor

A Novel Small Molecule Inhibitor for Aurora-A Kinase Inhibits the Growth of Cervical Cancer In Vitro and In Vivo.

2010 ◽  
Vol 83 (Suppl_1) ◽  
pp. 344-344
Author(s):  
Patricia Y. Akinfenwa ◽  
Nonna V. Kolomeyevskaya ◽  
Claire M. Mach ◽  
Zhen Li ◽  
Matthew L. Anderson
Keyword(s):  
Cervical Cancer ◽  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Molecule Inhibitor

scholarly journals A Small Molecule Inhibitor of the β-Catenin-TCF4 Interaction Suppresses Colorectal Cancer Growth In Vitro and In Vivo

EBioMedicine ◽  
2017 ◽  
Vol 25 ◽  
pp. 22-31 ◽  
Author(s):  
Seung Ho Shin ◽  
Do Young Lim ◽  
Kanamata Reddy ◽  
Margarita Malakhova ◽  
Fangfang Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Cancer Growth ◽  
Molecule Inhibitor

A G-Quadruplex-Interactive Potent Small-Molecule Inhibitor of Telomerase Exhibiting in Vitro and in Vivo Antitumor Activity

2002 ◽  
Vol 61 (5) ◽  
pp. 1154-1162 ◽  
Author(s):  
Sharon M. Gowan ◽  
John R. Harrison ◽  
Lisa Patterson ◽  
Melanie Valenti ◽  
Martin A. Read ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
In Vivo Antitumor Activity ◽  
Molecule Inhibitor ◽  
G Quadruplex

scholarly journals An acetyl-click screening platform identifies a small molecule inhibitor of Histone Acetyltransferase 1 (HAT1) with anti-tumor activity

2021 ◽  
Author(s):  
Joshua J Gruber ◽  
Amith Rangarajan ◽  
Tristan Chou ◽  
Benjamin S. Geller ◽  
Selene Banuelos ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Small Molecule ◽  
Cancer Metabolism ◽  
Human Cancer ◽  
Small Molecule Inhibitor ◽  
Cellular Growth ◽  
Acetyl Coa ◽  
Molecule Inhibitor

HAT1 is a central regulator of chromatin synthesis that acetylates nascent histone H3:H4 tetramers in the cytoplasm. It may have a role in cancer metabolism by linking cytoplasmic production of acetyl-CoA to nuclear acetyl flux. This is because the HAT1 di-acetylation mark is not propagated in chromatin and instead is de-acetylated after nascent histone insertion into chromatin. Thus, HAT1 likely provides a nuclear source of free acetate that may be recycled to acetyl-CoA for nuclear acetylation reactions. Correspondingly, suppression of HAT1 protein expression impairs tumor growth. To ascertain whether targeting HAT1 is a viable anti-cancer treatment strategy we sought to identify small molecule inhibitors of HAT1. We developed a high-throughput HAT1 acetyl-click assay to facilitate drug discovery and enzymology. Screening of small molecules computationally predicted to bind the active site led to the discovery of multiple riboflavin analogs that inhibited HAT1 enzymatic activity by competing with acetyl-CoA binding. These hits were refined by synthesis and testing over 70 analogs, which yielded structure-activity relationships. The isoalloxazine core was required for enzymatic inhibition, whereas modifications of the ribityl sidechain improved enzymatic potency and cellular growth suppression. These efforts resulted in a lead compound (JG-2016) that suppressed growth of human cancer cells lines in vitro and impaired tumor growth in vivo. This is the first report of a small molecule inhibitor of the HAT1 enzyme complex and represents a step towards targeting this pathway for cancer therapy.

scholarly journals The Jak2 Small Molecule Inhibitor, G6, Reduces the Tumorigenic Potential of T98G Glioblastoma Cells In Vitro and In Vivo

PLoS ONE ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. e105568 ◽  
Author(s):  
Rebekah Baskin ◽  
Sung O. Park ◽  
György M. Keserű ◽  
Kirpal S. Bisht ◽  
Heather L. Wamsley ◽  
...  
Keyword(s):  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Glioblastoma Cells ◽  
Molecule Inhibitor ◽  
Tumorigenic Potential

scholarly journals Small-molecule inhibitor targeting the Hsp90-Cdc37 protein-protein interaction in colorectal cancer

2019 ◽  
Vol 5 (9) ◽  
pp. eaax2277 ◽  
Author(s):  
Lei Wang ◽  
Lixiao Zhang ◽  
Li Li ◽  
Jingsheng Jiang ◽  
Zhen Zheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Small Molecule ◽  
Protein Interaction ◽  
Small Molecule Inhibitor ◽  
Protein Protein Interaction ◽  
Molecule Inhibitor ◽  
Dependent Cell ◽  
Hsp90 Chaperone

Disrupting the interactions between Hsp90 and Cdc37 is emerging as an alternative and specific way to regulate the Hsp90 chaperone cycle in a manner not involving adenosine triphosphatase inhibition. Here, we identified DDO-5936 as a small-molecule inhibitor of the Hsp90-Cdc37 protein-protein interaction (PPI) in colorectal cancer. DDO-5936 disrupted the Hsp90-Cdc37 PPI both in vitro and in vivo via binding to a previously unknown site on Hsp90 involving Glu47, one of the binding determinants for the Hsp90-Cdc37 PPI, leading to selective down-regulation of Hsp90 kinase clients in HCT116 cells. In addition, inhibition of Hsp90-Cdc37 complex formation by DDO-5936 resulted in a remarkable cyclin-dependent kinase 4 decrease and consequent inhibition of cell proliferation through Cdc37-dependent cell cycle arrest. Together, our results demonstrated DDO-5936 as an identified specific small-molecule inhibitor of the Hsp90-Cdc37 PPI that could be used to comprehensively investigate alternative approaches targeting Hsp90 chaperone cycles for cancer therapy.

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