Methotrexate analogs. 22. Synthesis, dihydrofolate reductase affinity, cytotoxicity, and in vivo antitumor activity of some putative degradation products of methotrexate-poly(L-lysine) conjugates

1984 ◽  
Vol 27 (7) ◽  
pp. 888-893 ◽  
Author(s):  
Andre Rosowsky ◽  
Ronald A. Forsch ◽  
James H. Freisheim ◽  
John Galivan ◽  
Michael Wick
Keyword(s):  
Antitumor Activity ◽  
Dihydrofolate Reductase ◽  
Degradation Products ◽  
In Vivo Antitumor Activity

Synthesis, in vitro and in vivo antitumor activity of symmetrical bis-Schiff base derivatives of isatin

2014 ◽  
Vol 74 ◽  
pp. 742-750 ◽  
Author(s):  
Chengyuan Liang ◽  
Juan Xia ◽  
Dong Lei ◽  
Xiang Li ◽  
Qizheng Yao ◽  
...  
Keyword(s):  
Schiff Base ◽  
Antitumor Activity ◽  
Schiff Base Derivatives ◽  
In Vivo Antitumor Activity ◽  
Derivatives Of

Unprecedented sugar-dependent in vivo antitumor activity of carbohydrate-pendant cis-diamminedichloroplatinum(II) complexes

2001 ◽  
Vol 11 (23) ◽  
pp. 3045-3047 ◽  
Author(s):  
Yuji Mikata ◽  
Yoshie Shinohara ◽  
Kazumi Yoneda ◽  
Yuka Nakamura ◽  
Izabela Brudziñska ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
In Vivo Antitumor Activity

Novel water soluble phosphate prodrugs of taxol® possessing in vivo antitumor activity

1993 ◽  
Vol 3 (8) ◽  
pp. 1761-1766 ◽  
Author(s):  
Yasutsugu Ueda ◽  
Amarendra B. Mikkilineni ◽  
Jay O. Knipe ◽  
William C. Rose ◽  
Anna Maria Casazza ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Water Soluble ◽  
Soluble Phosphate ◽  
In Vivo Antitumor Activity

scholarly journals A brain-penetrant microtubule-targeting agent that disrupts hallmarks of glioma tumorigenesis

2020 ◽  
Author(s):  
Eric A Horne ◽  
Philippe Diaz ◽  
Patrick J Cimino ◽  
Erik Jung ◽  
Cong Xu ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Mouse Model ◽  
Immunofluorescence Analysis ◽  
In Vivo Antitumor Activity ◽  
Microtubule Targeting Agents ◽  
Mitotic Delay ◽  
Tumor Mouse Model ◽  
In Vivo Testing ◽  
New Chemical Entity

Abstract Background Glioma is sensitive to microtubule-targeting agents (MTAs), but most MTAs do not cross the blood brain barrier (BBB). To address this limitation, we developed the new chemical entity, ST-401, a brain-penetrant MTA. Methods Synthesis of ST-401. Measures of MT assembly and dynamics. Cell proliferation and viability of patient-derived (PD) glioma in culture. Measure of tumor microtube (TM) parameters using immunofluorescence analysis and machine learning-based workflow. Pharmacokinetics (PK) and experimental toxicity in mice. In vivo antitumor activity in the RCAS/tv-a PDGFB-driven glioma (PDGFB-glioma) mouse model. Results We discovered that ST-401 disrupts microtubule (MT) function through gentle and reverisible reduction in MT assembly that triggers mitotic delay and cell death in interphase. ST-401 inhibits the formation of TMs, MT-rich structures that connect glioma to a network that promotes resistance to DNA damage. PK analysis of ST-401 in mice shows brain penetration reaching antitumor concentrations, and in vivo testing of ST-401 in a xenograft flank tumor mouse model demonstrates significant antitumor activity and no over toxicity in mice. In the PDGFB-glioma mouse model, ST-401 enhances the therapeutic efficacies of temozolomide (TMZ) and radiation therapy (RT). Conclusion Our study identifies hallmarks of glioma tumorigenesis that are sensitive to MTAs and reports ST-401 as a promising chemical scaffold to develop brain-penetrant MTAs.

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