PMID: 11606124Oct 19, 2001Paper

Hydrophilic, pro-drug analogues of T138067 are efficacious in controlling tumor growth in vivo and show a decreased ability to cross the blood brain barrier

Journal of Medicinal Chemistry
S M RubensteinJ C Jaen

Abstract

The novel anticancer compound T138067 is an irreversible inhibitor of tubulin polymerization. Amides 3-6 were synthesized using standard methodologies and determined to be significantly less lipophilic than T138067 based on logP calculations. Tubulin polymerization and [(3)H]-T138067 competition assays revealed that these amides are pro-drugs for parent aniline 2. Amides 3-5 showed no detectable signs of crossing the blood brain barrier, while amide 6 was found in extremely small amounts (12 ng/g of brain tissue). Aniline 2, which was formed in vivo from these amides, was found in significantly smaller amounts (approximately 20 to >5000 times) in the brain than when 2 was administered directly. The in vivo efficacy of amide 6 approached that of T138067 and was better tolerated when administered to athymic nude mice bearing MX-1 human mammary tumor xenografts.

References

Oct 1, 1991·Pharmacology & Therapeutics·E K Rowinsky, R C Donehower
Jan 5, 1999·Bioorganic & Medicinal Chemistry Letters·J C MedinaJ C Jaen
Jan 5, 1999·Bioorganic & Medicinal Chemistry Letters·K OhsumiT Tsuji
May 13, 1999·Proceedings of the National Academy of Sciences of the United States of America·B ShanH Beckmann
Jul 16, 1999·Bioorganic & Medicinal Chemistry Letters·J C MedinaJ C Jaen

❮ Previous
Next ❯

Citations

Jul 21, 2012·Pharmaceutical Research·Yan LuDuane D Miller
Feb 26, 2004·Bioorganic & Medicinal Chemistry Letters·Xiangshu FeiGary D Hutchins
Jul 23, 2002·Current Opinion in Chemical Biology·Peter L Toogood
May 25, 2002·Epilepsia·Angélica M Bello-RamírezAlejandro A Nava-Ocampo
Aug 2, 2007·Biological & Pharmaceutical Bulletin·Masahiro OgataToyoshige Endo
Aug 11, 2010·Biomicrofluidics·Matteo Altissimo
Nov 1, 2012·Biotechnology Advances·Anil KumarXing-Jie Liang
Jun 14, 2005·Cancer Investigation·Federico Pellegrini, Daniel R Budman
Oct 21, 2015·Analytical Cellular Pathology (Amsterdam)·Daniele FanaleViviana Bazan
Sep 23, 2014·European Journal of Medicinal Chemistry·Ramandeep KaurJitender Bariwal
Mar 6, 2007·European Journal of Medicinal Chemistry·Zdzisław BrzozowskiJarosław Sławiński
Jun 18, 2014·Bioorganic & Medicinal Chemistry·Sonali SandhuGulshan Bansal
Oct 27, 2018·Medicinal Research Reviews·Alba Vicente-BlázquezRafael Peláez
Jun 19, 2019·Current Topics in Medicinal Chemistry·Yongtao DuanChuanjun Song
Mar 6, 2021·Critical Reviews in Oncology/hematology·Alja ZottelRadovan Komel
Nov 11, 2005·Journal of Medicinal Chemistry·Nicolas LebeguePascal Berthelot
Jan 22, 2005·Journal of Medicinal Chemistry·Ana B S MayaManuel Medarde
Dec 22, 2006·Journal of Medicinal Chemistry·Stephen A Hitchcock, Lewis D Pennington

❮ Previous
Next ❯

Related Concepts

Related Feeds

Breast Tumorigenesis

Breast tumorigenesis involves the production or formation of tumor(s) in breast tissue. Discover the latest research on breast tumorigenesis here.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.