scholarly journals In Vivo Validation of a Small Molecule Inhibitor of Tau Self-Association in htau Mice

2020 ◽  
Vol 73 (1) ◽  
pp. 147-161 ◽  
Author(s):  
Eliot J. Davidowitz ◽  
Pavan K. Krishnamurthy ◽  
Patricia Lopez ◽  
Heidy Jimenez ◽  
Leslie Adrien ◽  
...  
Keyword(s):  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Molecule Inhibitor ◽  
Self Association ◽  
In Vivo Validation

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

Preclinical evaluation of SC0245, a small molecule inhibitor of ATR kinase.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15642-e15642
Author(s):  
Jian Wang ◽  
Qi Li ◽  
Yuanfeng Xia ◽  
Chi-Chung Chan ◽  
Xusheng Yuan ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Mouse Models ◽  
Small Molecule ◽  
Kinase Inhibitor ◽  
Small Molecule Inhibitor ◽  
Inhibiting Activity ◽  
Molecule Inhibitor ◽  
Phosphoinositide 3 Kinase ◽  
Atr Kinase

e15642 Background: The ataxia telangiectasia and Rad3-related (ATR) kinase is a member of the phosphoinositide 3-kinase related kinase (PIKK) family. ATR plays an important role in maintaining genome integrity during DNA replication through the activation of Chk1, and regulation of the DNA damage response (DDR). Replication stress (RS) is a major source of genomic instability in cancer, and targeting the RS-response kinase ATR has emerged as a promising antitumor approach. The purpose of this study was to investigate the antitumor activity of SC0245, a small molecule inhibitor of ATR kinase, in preclinical models of ATM pathway or ARID1A deficient solid tumors. Methods: The kinase inhibiting activity of SC0245 was determined using the ATR/ATRIP(h) complex assays. The cellular anti-proliferative activity was evaluated with tumor cells which was ATM pathway or ARID1A deficient. The in vivo antitumor activity of SC0245 was evaluated in ATM pathway or ARID1A deficient cell-derived xenograft (CDX) mouse models of gastric cancer (SNU-601) and colorectal adenocarcinoma (LoVo). Results: SC0245 displayed potent kinase inhibiting activity for ATR/ATRIP complex with IC50 14 nM, and had outstanding selectivity in the 104 onco-kinase panels. SC0245 significantly inhibited cell proliferation in ATM pathway or ARID1A deficient LoVo cells with IC50 0.163 μM, SNU-601 cells with IC50 0.218 μM. SC0245 showed excellent pharmacokinetics (PK) features with oral bioavailability ( > 80%) in mouse, rat and dog. Moreover, in the SNU601 and LoVo CDX mouse models, SC0245 oral administration significantly inhibited tumor growth, with better efficacy than AZD6738. Conclusions: SC0245, a novel potent ATR kinase inhibitor, has marked antitumor efficacy in the ATM pathway or ARID1A deficient solid tumor animal models, and has outstanding PK properties. SC0245 represents a promising clinical candidate for treating solid cancers, such as gastric and colorectal cancers.

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
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